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Exhibit 10.9
CS93-27
FOR CLINICAL STUDY
Agreement, made this 11th day of February, 1993, by and between THE
UNIVERSITY OF TEXAS M.D. XXXXXXXX CANCER CENTER (hereinafter referred to as
"CANCER CENTER"), a component institution of The University of Texas System
(hereinafter referred to as "SYSTEM"), located in Houston, Texas, and Texas
Biomedical Development Partners (hereinafter referred to as "SPONSOR"), located
in Austin, Texas.
WITNESSETH:
WHEREAS, CANCER CENTER has research facilities and situations which
would allow clinical investigation and study of the "Clinical Protocol for
Modification of Oncogene and tumor Suppressor Gene Expression in Non-Small Cell
Lung Cancer (NSCLC)" as described in Exhibit I hereinafter referred to as
("Research"), a copy of which is attached hereto and incorporated herein by
reference; and
WHEREAS, both SPONSOR and CANCER CENTER consider it necessary and
desirable and desirable to perform the Research;
NOW, THEREFORE, the parties agree as follows:
1. Evaluation. SPONSOR agrees to engage the services of CANCER CENTER as an
independent contractor to perform the Research. The Research will be under the
supervision of Xxxx X. Xxxx, M.D. (Principal Investigator) at CANCER CENTER,
with the assistance of appropriate associates and colleagues at CANCER CENTER as
may be required.
2. Research. CANCER CENTER agrees as an independent contractor to conduct the
Research. Such Research was originally approved by CANCER CENTER in accordance
with CANCER CENTER policy and may be subsequently amended only in accordance
with CANCER CENTER policy and the written agreement of CANCER CENTER and SPONSOR
as provided for in Article 15 herein below.
3. Invention and Patents.
a. For all purposes herein, "Invention" shall mean any discovery,
concept or idea whether or not patentable or copyrightable, which (i) arises out
of work performed pursuant to the obligations of this Agreement; (ii) is
conceived and reduced to practice during the term of the Agreement as defined in
Article 13 hereinbelow; and (iii) includes but is not limited to processes,
methods, software, formulae, techniques, compositions of matter, devices, and
improvements thereof and know-how relating thereto. Inventions made solely by
the Principal Investigator and/or other CANCER CENTER personnel as identified in
Article 1 hereinabove or agents of CANCER CENTER shall be the sole property of
CANCER CENTER.
b. In the event that an Invention is made, CANCER CENTER agrees to
include such Invention in the Option Agreement of December 17, 1992 (attached
hereto as Exhibit III) previously
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entered in to by CANCER CENTER and SPONSOR and give notice of such Invention to
SPONSOR within thirty (30) days of the identification of such Invention.
4. Confidentiality. In the course of work performed pursuant to the Research
under this Agreement, should either party provide confidential information to
the other party, the recipient party shall, until three (3) years after the
termination of this Agreement, maintain the confidentiality of that information
as it maintains the confidentiality of its own confidential information, and
shall not disclose such confidential information to any other party, nor shall
the recipient party disclose the disclosing party's confidential information to
the recipient's employees other than those employees having a "need-to-know."
Confidential information shall be clearly marked as such. If disclosed orally,
the party making the disclosure shall be responsible for clearly informing the
recipient party of the confidentiality of the information disclosed.
Notwithstanding the other provisions of this paragraph, nothing disclosed
hereunder shall be construed as confidential information which:
a. is or becomes available to the public (except by a breach of this
Agreement by a party hereto);
b. is rightfully received from another party not under obligation of
confidentiality to the disclosing party;
c. is not known by the recipient party, or is independently developed
by the recipient party by persons without access to the confidential
information;
d. is approved for release by the party designating the information as
confidential;
e. is not identified as confidential at the time of disclosure;
f. is not in writing or physical form at time of disclosure or reduced
to a written or physical form and identified as confidential within thirty (30)
days of disclosure; or
g. is required to be disclosed under the laws of the United States of
America or the State of Texas or other governmental bodies, provided that the
parties shall first exhaust all reasonable measures available to protect the
confidentiality of such information upon disclosure.
5. Publication Rights. Notwithstanding the provisions of Article 4 of this
Agreement, CANCER CENTER may publish scientific papers relating to the
collaborative research performed under this Agreement. In the event that CANCER
CENTER wishes to publish, CANCER CENTER shall notify SPONSOR of its desire to
publish [ * ] in advance of publication and shall furnish to SPONSOR a written
description of the subject matter of the publication in order to permit SPONSOR
to review and comment thereon.
6. Publicity. CANCER CENTER acknowledges SPONSOR'S intention to distribute
periodically information releases and announcements to the news media regarding
the progress of research hereunder. SPONSOR shall not release such materials
containing the name of CANCER CENTER or any of its employees without prior
written approval by an authorized representative of CANCER CENTER, and
[*] Certain information on this page has been omitted and filed
separately with the Commission. Confidential treatment has been
requested with respect to the omitted portions.
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said approval shall not be unreasonably withheld. Should CANCER CENTER reject
the news release, CANCER CENTER and SPONSOR agree to discuss the reasons for
CANCER CENTER's rejection, and every effort shall be made to develop an
appropriate informational news release within the bounds of accepted academic
practices. SPONSOR reserves the same right in the event that CANCER CENTER
desires to distribute a news release concerning the research program. Nothing
herein shall be construed as prohibiting CANCER CENTER or SPONSOR from reporting
on this study to a governmental agency.
7. Responsibility. The parties each agree to assume individual responsibility
for the actions and omissions of their respective employee, agents and assigns
in conjunction with this evaluation.
8. Independent Contractor. SPONSOR will not have the right to direct or control
the activities of CANCER CENTER in performing the services provided herein, and
CANCER CENTER shall perform services hereunder only as an independent
contractor, and nothing herein contained shall be construed to be inconsistent
with this relationship or status. Under no circumstances shall CANCER CENTER be
considered to be an employee or agent of SPONSOR. This Agreement shall not
constitute, create or in any way be interpreted as a joint venture, partnership
or formal business organization of any kind.
9. Title to Equipment. CANCER CENTER shall retain title to all equipment
purchased and/or fabricated by it with funds provided by SPONSOR under this
Agreement.
10. Survivorship. The provisions of Articles 3, 4, 5, 6, and 12 shall survive
any expiration or termination of this Agreement.
11. Assignment. This Agreement may not be assigned by either party without the
prior written consent of the other party; provided, however, that SPONSOR may
assign this Agreement to any purchaser or transferee of all or substantially all
of SPONSOR's business upon prior written notice to CANCER CENTER.
12. Indemnification. CANCER CENTER shall, to the extent authorized under the
Constitution and the laws of the State of Texas, hold SPONSOR harmless from
liability resulting from the negligent acts or omissions of CANCER CENTER, its
agents or employees pertaining to the activities to be carried out pursuant to
the obligations of this Agreement; provided, however, that CANCER CENTER shall
not hold SPONSOR harmless from claims arising out of the negligence of SPONSOR,
its officers, agents or any person or entity not subject to CANCER CENTER's
supervision or control.
SPONSOR shall indemnify and hold harmless SYSTEM, CANCER CENTER, their regents,
officers, agents and employees from any liability or loss resulting from
judgments or claims against them arising out of the activities to be carried out
pursuant to the obligations of this Agreement or the use by SPONSOR of the
results of the Research, provided, however, that the following is excluded from
SPONSOR's obligation to indemnify and hold harmless:
a. the negligent failure of CANCER CENTER to comply with any applicable
governmental requirements; or
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b. the negligence or willful malfeasance by a regent, officer, agent or
employee of CANCER CENTER or SYSTEM.
13. Award. SPONSOR agrees to pay CANCER CENTER a fee of Five Hundred Fifteen
Thousand and No/100 Dollars ($515,000.00) for expenses and other related costs
incurred in conjunction with the Research. This fee, as shown by approximate
category of expense in Exhibit II, which is attached hereto and is incorporated
herein by reference, for information only, shall be payable in Four (4) equal
installments of One Hundred Twenty-Eight Thousand Seven Hundred Fifty and No/100
Dollars ($128,750.00) each by SPONSOR to CANCER CENTER. The first such
installment shall be due within thirty (30) days of the date of execution of
this Agreement. The subsequent installments shall be due and payable as follows:
(a) three (3) months after execution, (b) six (6) months after execution and (c)
nine (9) months after execution.
14. Basic Term. This Agreement shall become effective as of the date first
hereinabove written and unless earlier terminated as hereinafter provided, shall
continue in force for a period of Eighteen (18) months after the same.
15. Default and Termination. In the event that either party to this Agreement
shall be in default of any of its material obligations hereunder and shall fail
to remedy such default within [*] after receipt of written notice thereof, the
party not in default shall have the option of terminating this Agreement by
giving written notice thereof, notwithstanding anything to the contrary
contained in this Agreement. Termination of this Agreement shall not affect the
rights and obligations of the parties which accrued prior to the effective date
of termination. SPONSOR shall pay CANCER CENTER for all reasonable expenses
incurred or committed to be expended as of the effective termination date,
subject to the maximum amount as specified in Article 13.
16. Entire Agreement. The parties acknowledge that this Agreement and the
attached Exhibits hereto represent the sole and entire Agreement between the
parties hereto pertaining to the Research and that such supersedes all prior
Agreements, understandings, negotiations and discussions between the parties
regarding same, whether oral or written. There are no warranties,
representations or other Agreements between the parties in connection with the
subject matter hereof except as specifically set forth herein. No supplement,
amendment, alteration, modification, waiver or termination of this Agreement
shall be binding unless executed in writing by the parties hereto.
17. Reform of Agreement. If any provision of this Agreement is, becomes or is
deemed invalid, illegal or unenforceable in any United States jurisdiction, such
provision shall be deemed amended to conform to applicable laws so as to be
valid and enforceable; or if it cannot be so amended without materially altering
the intention of the parties, it shall be stricken, and the remainder of this
Agreement shall remain in full force and effect.
18. Notices. Any notices, statements, payments, or reports required by this
Agreement shall be considered given if sent by United States Certified Mail,
postage prepaid and addressed as follows:
If to CANCER CENTER:
Xxxxxxx X. Best
Chief Financial Officer
The University of Texas M.D. Xxxxxxxx Cancer Center
0000 Xxxxxxxx Xxxx.
Xxxxxxx, Xxxxx 00000
[*] Certain information on this page has been omitted and filed
separately with the Commission. Confidential treatment has been
requested with respect to the omitted portions.
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If to SPONSOR:
Xxxxx Xxxxx
Managing Partner
Texas Biomedical Development Partners
000 Xxxxxxxx Xxxxxx, Xxxxx 000
Xxxxxx, Xxxxx 00000
19. Captions. The captions in this Agreement are for convenience only and shall
not be considered a part of or affect the construction or interpretation of any
provision of this Agreement.
20. Governing Law. This Agreement shall be governed and interpreted in
accordance with the substantive laws of the State of Texas and with applicable
laws of the United States of America.
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IN WITNESS WHEREOF, CANCER CENTER and SPONSOR entered into this
Agreement effective as of the date first hereinabove written and have executed
three (3) originals each of which are of equal dignity.
TEXAS BIOMEDICAL DEVELOPMENT THE UNIVERSITY OF TEXAS
PARTNERS M.D. XXXXXXXX CANCER CENTER
By: /s/ XXXXX XXXXX By /s/ XXXXXXX X. BEST
------------------------------- ---------------------------------
Xxxxx Xxxxx Xxxxxxx X. Best
Managing Partner Chief Financial Officer
I have read this agreement
and understand my
obligations hereunder: CONTENT APPROVED:
By: /s/ XXXX X. XXXX By: /s/ XXXXX X. XXXXXXX
------------------------------- ---------------------------------
Xxxx X. Xxxx, M.D. Xxxxx X. Xxxxxxx, CPA
Principal Investigator Manager, Sponsored Agreements
FORM APPROVED:
By: /s/ XXXXXXX X. XXXXX By: /s/ XXXXXXX X. XXXX
------------------------------- ---------------------------------
Xxxxxxx X. Xxxxx, M.D. Xxxxxxx X. Xxxx, X.X.
Head, Division of Surgery Legal Services Officer
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BUDGET FOR PROTOCOL
[ * ]
[*] Certain information on this page has been omitted and filed
separately with the Commission. Confidential treatment has been
requested with respect to the omitted portions.
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AMENDMENT NO. 1
TO
RESEARCH AGREEMENT
This Amendment No. 1 to Research Agreement ("AMENDMENT") is made and
entered into as of July 20, 1994 by and between INTRON THERAPEUTICS, INC., a
Delaware Corporation ("SPONSOR") and THE UNIVERSITY OF TEXAS M.D. XXXXXXXX
CANCER CENTER ("CANCER CENTER"), a component institution of the University of
Texas System ("SYSTEM").
RECITALS
1. SPONSOR and CANCER CENTER entered into a FOR
CLINICAL STUDY, number CS 93-27, dated as of February 11, 1993 (the "RESEARCH
AGREEMENT').
2. SPONSOR, CANCER CENTER and the Regents of the University of Texas System have
entered into a PATENT AND TECHNOLOGY LICENSE AGREEMENT dated as of July 20, 1994
(the "LICENSE AGREEMENT").
3. CANCER CENTER and SPONSOR wish to extend the term of the RESEARCH AGREEMENT,
acknowledge that the RESEARCH to be conducted thereunder will include matters
beyond the clinical trial protocol attached to the RESEARCH AGREEMENT as
originally executed, and that SPONSOR will have the option to include within the
LICENSED SUBJECT MATTER under the LICENSE AGREEMENT any intellectual property
that is made in the course of performing under the RESEARCH.
NOW, THEREFORE, it is hereby agreed as follows:
a. DEFINITIONS. Any capitalized terms that are not otherwise defined
herein shall be as in the RESEARCH AGREEMENT or the LICENSE AGREEMENT. In
addition, for all purposes of this AGREEMENT, the term "RESEARCH" shall be
deemed to include all work of CANCER CENTER personnel in performing the clinical
trial described int he protocol attached as Exhibit 1 and as modified from time
to time, as well as any work that is performed by Xx. Xxxx X. Xxxx or other
CANCER CENTER personnel comprising additional research projects described in
Attachment A-n, where n represents the ordinal number of a particular project.
b. Invention and Patents. Section 3 of the RESEARCH AGREEMENT shall be
amended as follows:
1. So much of Section 3(a) of the RESEARCH AGREEMENT as reads
"(i) arises out of work performed pursuant to the obligations of this AGREEMENT'
is hereby amended to read "(i) arises out of the Research;".
2. Paragraph (b) of Section 3 is hereby deleted and replaced
in its entirety with the following:
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"b. In the event that an Invention is made, CANCER CENTER
shall notify SPONSOR, which notice shall reference
this Section 3 and include a description of the
Invention in reasonable detail. SPONSOR shall have
the-option to include all worldwide patent rights
with respect to such Invention within the "EXISTING
PATENT RIGHTS" under Section 2.3(a) of the LICENSE
AGREEMENT," and to include related information,
know-how, biological materials and the like within
the TECHNOLOGY RIGHTS under the LICENSE AGREEMENT. To
exercise such option with respect to any particular
Invention, SPONSOR shall so notify CANCER CENTER
within 120 days after receipt of CANCER CENTER's
notice thereof as described above. Promptly following
such exercise, the parties shall revise Schedule A to
the LICENSE AGREEMENT to reflect the additional
patent applications so included. CANCER CENTER
warrants to SPONSOR that CANCER CENTER has the right
to grant to SPONSOR the option and rights
contemplated in this Section 3 and that upon exercise
of the option described herein with respect to any
Invention, all worldwide patent rights therein will
be included under the LICENSE AGREEMENT."
c. Term. Section 14 of the RESEARCH AGREEMENT is hereby amended by
adding to the end thereof the following: "Following such initial Eighteen (18)
month period, unless earlier terminated as provided in Section 15, this
Agreement shall continue in full force and effect until terminated by either
party for any reason on ninety (90) days prior written notice to the other
party."
d. Other. Except as expressly provided in this AMENDMENT, all other
terms, conditions and provisions of the RESEARCH AGREEMENT shall continue in
effect as provided therein.
IN WITNESS WHEREOF, CANCER CENTER and SPONSOR entered into this
AMENDMENT effective as of the date first hereinabove written and have executed
three (3) originals each of which are of equal dignity.
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IN WITNESS WHEREOF, each of the parties has executed this Amendment as
of the date first above written.
TEXAS BIOMEDICAL DEVELOPMENT THE UNIVERSITY OF TEXAS
PARTNERS M.D. XXXXXXXX CANCER CENTER
By: /s/ XXXXX XXXXX By /s/ XXXXXXX X. BEST
------------------------------- ---------------------------------
Xxxxx Xxxxx Xxxxxxx X. Best
Managing Partner Chief Financial Officer
I have read this agreement
and understand my
obligations hereunder: CONTENT APPROVED:
By: /s/ XXXX X. XXXX By: /s/ XXXXX X. XXXXXXX
------------------------------- ---------------------------------
Xxxx X. Xxxx, M.D. Xxxxx X. Xxxxxxx, CPA
Principal Investigator Manager, Sponsored Agreements
FORM APPROVED:
By: /s/ XXXXXXX XXXXXXXX By: Not applicable
------------------------------- ---------------------------------
Xxxxxxx Xxxxxxxx, M.D. Xxxxxxx X. Xxxx, X.X.
Head, Division of Surgery and Legal Services Officer
Anesthesiology (Ad interim)
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EXHIBIT 1
PROTOCOL
[*]
[*] Certain information on this page has been omitted and filed
separately with the Commission. Confidential treatment has been
requested with respect to the omitted portions.
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AMENDMENT NO. 2
TO
CLINICAL STUDY AGREEMENT
STATE OF TEXAS
COUNTY OF XXXXXX
AMENDMENT, effective this 1st day of January, 1995, between THE
UNIVERSITY OF TEXAS M.D. XXXXXXXX CANCER CENTER (hereinafter referred to
as"CANCER CENTER"), a component of THE UNIVERSITY OF TEXAS SYSTEM (hereinafter
referred to as "SYSTEM") located at Houston, Texas, and INTROGEN THERAPEUTICS,
formerly Intron Therapeutics, Inc. (hereinafter referred to as "SPONSOR"), of
the Clinical Study Agreement made by these parties and dated the 11th day of
February, 1993 and amended the 20th day of July, 1994, regarding research on the
evaluation and study of the "Clinical Protocol for Modification of Tumor
Supressor Gene Expression in Non-Small Cell Lung Cancer with a Retroviral Vector
Expressing Wildtype (normal) p53).
1. CANCER CENTER and SPONSOR agree that the period of work identified in the
original Clinical Study Agreement shall be extended to the later of February 29,
1996 or the completion of the project.
2. CANCER CENTER and SPONSOR agree that the work to be done during this extended
work period will be performed according to the procedures described in the
revised workscope, the title of which is "Clinical Protocol for Modification of
Tumor Supressor Gene Expression in Non-Small Cell Lung Cancer with a Retroviral
Vector Expressing Wildtype (normal) p53", a copy of which is attached hereto as
Exhibit I and incorporated herein by reference. The workscope has been amended
and approved in accordance with institutional policy. The Clinical Study
Agreement may be extended by the SPONSOR upon notification to CANCER CENTER and
Investigator to provide CANCER CENTER and Investigator with the funds needed to
complete the research provided the research is within the workscope as herein
described.
3. CANCER CENTER and SPONSOR agree that the specific additional costs associated
with this work [ * ].
4. SPONSOR and CANCER CENTER agree that payment of amounts by SPONSOR shall be
made [ * ].
OTHERWISE, the terms and provisions of the original Agreement executed
on the 11th day of February, 1993 and amended on the 20th day of July, 1994 by
and between the parties hereto shall remain in full force and effect, provided,
however, that in the event of a conflict in the terms and conditions between
this Amendment No. 2 and the Clinical Study Agreement, the terms and conditions
of this Amendment shall prevail.
[*] Certain information on this page has been omitted and filed
separately with the Commission. Confidential treatment has been
requested with respect to the omitted portions.
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IN WITNESS WHEREOF, the parties have executed two (2) original
counterparts of this Amendment No. 2, each of which are of equal dignity and
effective as of the date first hereinabove written.
INTROGEN THERAPEUTICS THE UNIVERSITY OF TEXAS
M.D. XXXXXXXX CANCER CENTER
By: /s/ XXXXX XXXXX By /s/ XXXXX X. XXXXXXX
------------------------------- ----------------------------------
Xxxxx Xxxxx Xxxxx X. Xxxxxxx, CPA
President Manager, Sponsored Programs
Date: 6/24/95 Date: 6/22/95
----------------------------- -------------------------------
I have read this agreement and
understand my obligations hereunder:
By: /s/ XXXX X. XXXX
----------------------------------
Xxxx X. Xxxx, M.D.
Principal Investigator
By: /s/ XXXXXXX XXXXXXXX
----------------------------------
Xxxxxxx Xxxxxxxx, M.D.
Ad Interim Head, Div. of Surgery
Payment Mailing Address:
The University of Texas
M.D. Xxxxxxxx Cancer Center
Attn.: Manager, Sponsored Programs
X.X. Xxx 000000
Xxxxxxx, Xxxxx 00000
Tax ID: 74-6001118-A1
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EXHIBIT 2
BUDGET
[ * ]
[*] Certain information on this page has been omitted and filed
separately with the Commission. Confidential treatment has been
requested with respect to the omitted portions.
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AMENDMENT NO. 3
TO
CLINICAL STUDY AGREEMENT
AMENDMENT, effective this 31st day of December, 1995, between THE
UNIVERSITY OF TEXAS M.D. XXXXXXXX CANCER CENTER (hereinafter referred to as
"CANCER CENTER"), a component of THE UNIVERSITY OF TEXAS SYSTEM (hereinafter
referred to as "SYSTEM") located at Houston, Texas, and INTROGEN THERAPEUTICS
(hereinafter referred to as "SPONSOR"), of the made
by these parties and dated the 11th day of February, 1993 and subsequently
amended, regarding research on the evaluation and study of the tumor suppressor
gene expression in non-small cell lung cancer.
1. CANCER CENTER and SPONSOR agree that the period of work identified in the
original Clinical Study Agreement shall be extended to December 31, 1996.
Thereafter, this Agreement can be extended for additional annual periods upon
the mutual written consent of CANCER CENTER and SPONSOR.
2. CANCER CENTER and SPONSOR agree that the work to be done during this extended
work period will be performed according to the procedures described in the
additional Protocol, the title of which is "Modification of Tumor Suppressor
Gene Expression and Induction of Apoptosis in Non-Small Cell Lung Cancer (NSCLC)
with an Adenovirus Vector Expressing Wildtype p53 and Cisplatin," a copy of
which is attached hereto as Exhibit I and incorporated herein by reference. The
Protocol has been approved in Accordance with institutional policy.
3. Award. During the term of this Amendment as set forth herein and in
consideration for CANCER CENTER's performance of the Protocol, SPONSOR agrees to
pay CANCER CENTER a fee [ * ].
4. ACCESS TO INFORMATION. All results of and information arising from the
Research shall be made available and accessible to SPONSOR by CANCER CENTER.
SPONSOR shall have the right to obtain copies or duplicates of such results and
information on a timely basis, in either written or electronic form, upon
SPONSOR giving CANCER CENTER reasonable notice of SPONSOR's desire to obtain
such results and information.
OTHERWISE the terms and provisions of the original Agreement executed
on the 11th day of February, 1993 and subsequently amended by and between the
parties hereto shall remain in full force and effect, provided, however, that in
the event of a conflict in the terms and conditions between this Amendment No. 3
and the Clinical Study Agreement, the terms and conditions of this Amendment
shall prevail.
[*] Certain information on this page has been omitted and filed
separately with the Commission. Confidential treatment has been
requested with respect to the omitted portions.
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IN WITNESS WHEREOF, the parties have executed two (2) original
counterparts of this Amendment No. 3, each of which are of equal dignity and
effective as of the date first hereinabove written.
INTROGEN THERAPEUTICS THE UNIVERSITY OF TEXAS
M.D. XXXXXXXX CANCER CENTER
By: /s/ XXXXX XXXXX By /s/ XXXXX X. XXXXXXX
------------------------------- ----------------------------------
Xxxxx Xxxxx Xxxxx X. Xxxxxxx, CPA
President Manager, Sponsored Programs
Date: 12/28/95 Date: 12/31/95
----------------------------- -------------------------------
I have read this agreement and
understand my obligations hereunder:
By: /s/ XXXX X. XXXX
----------------------------------
Xxxx X. Xxxx, M.D.
Principal Investigator
By: /s/ XXXXXXX XXXXXXXX
----------------------------------
Xxxxxxx Xxxxxxxx, M.D.
Ad Interim Head, Div. of Surgery
Payment Mailing Address:
The University of Texas
M.D. Xxxxxxxx Cancer Center
Attn.: Manager, Sponsored Programs
X.X. Xxx 000000
Xxxxxxx, Xxxxx 00000
Tax ID: 74-6001118-A1
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PROTOCOL
[ * ]
THE UNIVERSITY OF TEXAS M.D. XXXXXXXX CANCER CENTER
INFORMED CONSENT
Protocol Title: Clinical Protocol for Modification of Tumor Suppressor Gene
Expression in Non-Small Cell Lung Cancer (NSCLC) with a
Retroviral Vector Expressing Wildtype (normal) p53
1.
--------------------- -----------------
Participant's Name I.D. Number
You have the right to know about the procedures that are to be used in your
participation in clinical research so as to afford you an opportunity to make
the decision whether or not to undergo the procedure after knowing the risks
and hazards involved. This disclosure is not meant to frighten or alarm you; it
is simply an effort to make you better informed so that you may give or
withhold your consent to participate in clinical research. This informed
consent does not supersede other consents you may have signed.
DESCRIPTION OF RESEARCH
2. PURPOSE OF THE STUDY: Some lung cancers seem to arise because problems
occur in a part of the cells (a particular gene called "p53") that usually
stops cancer. In this clinical research study the investigators are trying
to insert a normal copy of the p53 gene into the lung cancer cells to see
if this will cause the cancer cells to stop growing. As a "vector", that
is, as a vehicle to get the p53 gene into the cells, the investigators will
use a retrovirus (a modified leukemia virus) that has been altered so it
cannot reproduce itself. Because the investigators are at an early stage in
the research, the investigators do not expect to cure the patients who
participate; instead, the immediate purpose of the study is to find out
what dose of vector can be used without harming patients and whether the
introduced p53 genes will cause cancer cells to stop growing.
3. DESCRIPTION OF RESEARCH: The experimental protocol is as follows: Patients
for this study will be selected from among patients with non-small cell
lung cancer who are not now candidates for radiation therapy or surgery.
Patients with local tumors that cannot be removed with surgery or have
recurred after radiation can participate. It is not necessary that the
patient received chemotherapy (drugs) alone but-chemotherapy may be an
alternative treatment. These tumors will be directly injected with the
retrovirus. Patients who have known tumors within their airway can also
participate. These patients are scheduled to have bronchoscopic exams as
part of their evaluation under either local anesthesia or general
anesthesia. The surgeon performs an examination using a regular white light
source to illuminate the tracheobronchial tree. If a tumor is found that is
obstructing a
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[*] Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to
the omitted portions.
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portion of the tracheobronchial tree, that patient will be considered
eligible for the study. It must also be possible to reduce the number of
tumor cells to a small amount, with removal through the bronchoscope or
laser treatment. Costs directly related to this research will not be the
responsibility of the patient. These costs will be the responsibility of
the sponsor of this research.
The tumor must have a specific gene mutation in it. It may be possible to
find this mutation in specimens from previous biopsies. However, if these
are not available, new biopsies must be performed. If the new biopsy
material does not show the mutation, the patient cannot participate in the
study. The residual tumor will be injected daily for 5 consecutive days
with a retrovirus containing a gene that may be able to correct an
abnormality detected in the cancer cells. This treatment may be repeated in
three months as long as there is evidence that the tumor is not growing and
that the treatment appears safe. The cost of the routine bronchoscopy and
biopsies which are part of the work up of patient's condition shall be
his/her responsibility. A maximum of 14 patients will be entered in the
study.
The investigators wish to follow the patient's medical condition for the
rest of the patient's life. If the patient should move, the patient should
notify Xx. Xxxx'x office.
PERMISSION FOR AUTOPSY: In case of death, the family of the patient will be
asked for an autopsy because an accurate documentation of the precise cause
of death may be important to all future patients.
4. RISKS, SIDE EFFECTS AND DISCOMFORTS TO PARTICIPANTS
A few additional biopsies will be required. A bronchoscopic biopsy samples
a very tiny piece of the mucosa inside the lung. Risks of biopsies include
hemoptysis (coughing up blood), which is usually transient and self
limited. Severe hemorrhage requiring emergency maneuvers such as intubation
and thoracotomy is exceedingly rare. Although extremely rare, any
experimental procedure may result in unforeseen risks. Appropriate medical
therapy will be made available for the treatment of such side effects.
4a. This clinical procedure may involve unforeseeable risks to unborn
children, therefore, the participants should practice adequate methods
of birth control throughout the period of their involvement in the
clinical study if they are sexually active. To help prevent injury to
children, the female participants should refrain from breast feeding
during participation in the clinical research study.
4b. Possibility of Causing a New Cancer. It is possible that the research
could cause cancer in normal cells but the investigators believe the
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risk is very small particularly because the investigators test the
material that is injected to make sure it does not contain
disease-causing viruses.
Risk from murine retrovirus. The retrovirus derived from the Xxxxxxx
murine leukemia virus is modified so that it no longer contains intact
viral genes. Thus it cannot produce an intact infectious virus.
Therefore, the risk of getting a virus infection is extremely low.
4c. A small amount of protamine is added to the retroviral mixture.
Infrequent allergic reactions and low blood pressure have occurred as
side-effects when this drug is given. These are very unlikely to occur
with the small dose given.
5. POTENTIAL BENEFITS: The primary purposes of this study are scientific,
namely, to test the safety of the procedure and to see whether the injected
gene will function in the cancer cells. If this happens, there might be a
potential therapeutic benefit to subjects, depending on how much of their
cancer is destroyed. It is possible that injection of the retrovirus will
slow the growth of the tumor and prevent further blockage of the lung. The
main benefit expected is advancing knowledge and developing future studies
and treatments rather than curing the patient-subjects who participate in
this study, although that is always a possibility.
6. ALTERNATE PROCEDURES OR TREATMENTS: Patients will be eligible for this
study if conventional therapy such as surgery or external beam radiation
therapy has already been performed or cannot be done.
UNDERSTANDING OF PARTICIPANTS
7. I have been given an opportunity to ask any question concerning the
procedure involved and the investigator has been willing to reply to my
inquiries. This procedure will be administered under the above numbered,
titled and described clinical research protocol at this institution. I
hereby authorize Xx. Xxxx X. Xxxx, the attending physician/investigator,
and designated associates to administer the treatment.
8. I have been told and understand that my participation in this clinical
research study is voluntary. I may decide not to participate, or withdraw
my consent and discontinue my participation at any time. Such action will
be without prejudice and there shall be no penalty or loss of benefits to
which I may otherwise be entitled, and I will continue to receive treatment
by my physician at this institution.
Should I decide not to participate or withdraw my consent from
participation in this clinical research, I have been advised that I should
discuss the
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consequences or effects of my decision with my physician.
In addition, I understand that the investigator may discontinue the
clinical research study if, in the sole opinion and discretion of the
investigator, the study or treatment offers me little or no future benefit,
or the supply of medication ceases to be available or other causes prevent
continuation of the clinical research study. The investigator will notify
me should such circumstances arise and my physician will advise me about
available treatments which may be of benefit at that time.
I will be informed of any new findings developed during the course of this
clinical research study which might be relevant to my willingness to
continue participation in the study.
9. I have been assured that confidentiality will be preserved, except that
qualified monitors from Microbiological Associates, Inc., the Food and Drug
Administration, or National Cancer Institute may review my records where
appropriate and necessary. Qualified monitors shall include assignees
authorized by the Surveillance Committee of this institution provided that
confidentiality is assured and preserved. My name will not be revealed in
any reports or publications resulting from this study without my expressed
consent.
10. I have been informed that, should I suffer any injury as a result of
participation in this research activity, reasonable medical facilities are
available for treatment at this institution. I understand, however, that I
cannot expect to receive any credit or reimbursement for expenses from this
institution or any financial compensation from this institution for such
injury.
11. I have been informed that I should inquire of the attending physician
whether or not there are any services, investigational agents or devices,
and/or medications being offered by the sponsor of this clinical research
project at a reduced cost or without cost.
Costs related to my medical care, including expensive tests or procedures
that may be required by this clinical research study, shall be my
responsibility unless the sponsor or other agencies contribute toward said
costs. Clarification of specific cost issues may be addressed in section 3
of this informed consent. I have been given the opportunity to discuss the
expenses or costs associated with my participation in this research
activity.
12. It is possible that this research project will result in the development of
beneficial treatments, devices, new drugs, or possible patentable
procedures, in which event I understand that I cannot expect to receive any
compensation or benefits from the subsequent use of information acquired
and development through my participation in this research project.
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13. I understand that refraining from breast feeding and practicing effective
contraception is medically necessary and a prerequisite for my
participation in this clinical research study. Should contraception be
interrupted or if there is any suspicion of pregnancy, my participation in
this clinical research study will be terminated at the sole discretion of
the investigator.
14. I may discuss any questions or problems during or after this study with
Xx. Xxxx X. Xxxx at (000) 000-0000. In addition, I may discuss any
problems I may have or any questions regarding my rights during or after
this study with the Chairman or the Surveillance Committee at
(000) 000-0000 and may in the event any problem arises during this clinical
research contact the parties named above.
CONSENT
Based upon the above, I consent to participate in the research and have
received a copy of the consent form.
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DATE SIGNATURE OF PARTICIPANT
------------------------- ---------------------------
WITNESS OTHER THAN PHYSICIAN SIGNATURE OF PERSON
OR INVESTIGATOR RESPONSIBLE & RELATIONSHIP
I have discussed this clinical research study with the Participant and/or his
or her authorized representative using language which is understandable and
appropriate. I believe that I have fully informed this participant of the
nature of this study and its possible benefits and risks, and I believe the
participant understood this explanation.
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PHYSICIAN/INVESTIGATOR
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