BMS INFORMED CONSENT FORM (ICF) FOR EARLY ACCESS TO MEDICINE
(NIVOLUMAB, RENAL CELL CARCINOMA)
Protocol Number:
CA209-588
Program Title:
EARLY ACCESS TO MEDICINE – NIVOLUMAB – FOR
ADVANCED/METASTATIC RENAL CELL CARCINOMA
Language:
English
Program Doctor’s Identification
Program Doctor’s full name: ___________________________________________
Address: ________________________________________________________________________
Telephone or other contact details: ____________________________________________________
1)
Participation
You are being asked to participate in an Early Access to Medicines Scheme (EAMS). Your eligibility
to take part in this program is decided based on specific eligibility criteria which your doctor will have
considered and discussed with you before obtaining your consent. Before you can take part in this
program, however, it is important that you understand what this program involves. Please read this
information carefully and ask your doctor any questions that you might have.
2)
Purpose of the Program
The purpose of this program is to provide patients with renal cell carcinoma (RCC) access to
nivolumab. Nivolumab is an antibody (a type of human protein) that is being tested in clinical trials to
see if it will allow the body’s immune system to work against cancer cells. Nivolumab is currently not
approved by the European Medicines Agency (EMA) for the treatment of renal cell carcinoma (RCC)
3)
Approximate Number of Participants and the Expected Duration of Your
Participation in the Program
The number of patients in this program will vary and will depend on the number of requests received
from UK hospitals.
Even though you may meet all the criteria for participation, it is possible that you will not be enrolled
in this program.
If you are enrolled, the duration of your participation will depend on your response to treatment. If you
continue to get benefit from treatment, BMS will provide nivolumab free of cost/charge up to the time
when nivolumab is reimbursed for use in the NHS in this setting or for a maximum of one year from
the date of approval by the European Medicine Agency (EMA), whichever comes sooner.
Once nivolumab receives approval by the European Medicine Agency for the treatment of RCC, no
new patients will be permitted to sign an informed consent, and enrollment in the program will stop.
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(NIVOLUMAB, RENAL CELL CARCINOMA)
Program Treatments
4)
Nivolumab is given as a slow injection (infusion), in a solution through a needle inserted into a vein.
The infusion usually takes about 1 hour (60 minutes). An infusion pump will be used to ensure the
correct amount of medicine is given over the proper amount of time.
Upon entry into the program, you will receive 3 mg/kg of nivolumab every 2 weeks. The total amount
of drug you will get in one infusion depend on your weight.
You will receive your first dose of nivolumab solution at Day 1. You may receive additional doses of
nivolumab every 2 weeks thereafter, depending on your response to the medicine and how well you
tolerate this treatment.
Program Procedures
5)
For further information about the procedures in the program, please refer to the document ‘Early
Access to Medicines Scheme - Treatment Protocol Information for patients’
The period between each treatment with the program medication is called a cycle. A cycle is defined
as 2 weeks (14 days) in this program.
You will be treated with 3 mg/kg of nivolumab IV. Nivolumab will be given to you as a slow injection
over 60-minutes on Day 1 and every 2 weeks (14 days) thereafter.
At each visit that you receive program medication and assessment of side effects that you may be
having.
If you experience any changes in your body or develop any new or worsening side effects during or
after treatment with nivolumab, you should inform the program doctor or nurse immediately.
If you experience side effects, you may be asked to return to the clinic more frequently (for example,
every 1-2 weeks) or you may be kept in the hospital until the side effects improve. You may be asked
to stop taking the program drugs.
It is possible that you will be required to stop program treatment early if nivolumab is not working as
expected or if you have unacceptable side effects. Your doctor will discuss this with you if this occurs.
Your Responsibilities
6)
During the treatment period, you will be asked to return to your doctor’s office or clinic as outlined
above.
At each visit:

You will be asked to take the program drugs as instructed.

You will be asked how you feel and if you have experienced any possible side effects. Your
doctor may prescribe medications to help control some of the side effects.
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BMS INFORMED CONSENT FORM (ICF) FOR EARLY ACCESS TO MEDICINE
(NIVOLUMAB, RENAL CELL CARCINOMA)

Tell the program doctor about all medications you are taking including prescriptions, herbal
supplements, and over-the-counter medications, since other medications can change how the
program drug works.

Discuss any medication (prescription or over the counter) that you wish to start taking with
your program doctor before you start taking it. Certain medications cannot be taken while you
are in this program. Your program doctor will explain what these medications are.

Tell the program doctor about any changes in your health.

Tell your program doctor about any medical treatments that you plan to receive during the
program (such as elective surgery or radiation).

Tell your program doctor or program staff if you change your address, telephone number, or
other contact information.
If you have any questions or concerns about the medications used in this program, you can contact
your doctor or a member of your doctor’s staff at any time.
You must always carry with you the Patient Alert Card that you will be given by your program
doctor.
7)
Risks / Possible Adverse Drug Reactions
For further information, please refer to the document ‘Early Access to Medicines Scheme - Treatment
Protocol: Information for Patients’.
8)
Risks to Reproduction, Unborn Babies and Nursing Infants
8A. General Statement
You must not be pregnant or breastfeeding, and you should not become pregnant or breastfeed
while you are taking the program treatments. Females should not breastfeed while receiving
nivolumab and up to 18 weeks from the last dose of nivolumab. You must use an adequate
method(s) to avoid pregnancy for the duration of this program and for up to 23 weeks after the
last dose of program drug. Male patients who are sexually active with a woman of child bearing
potential should also use an adequate method(s) of birth control to avoid pregnancy in their
partner for up to 31 weeks after the last dose of program drug. You should immediately contact
your program doctor if there is a change in your method of birth control to avoid pregnancy or if
you start any prescription drug or other medication (including over-the-counter drugs and herbal
supplements) not prescribed by the program doctor.
8B. Unforeseeable Risks
There may be unknown risks to you, your unborn baby, or nursing infant if you are or become
pregnant during this program or are breastfeeding during this program.
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8C. Laboratory & Animal Reproductive Toxicology Findings
While laboratory and animal studies have been conducted to determine possible risks, the results
do not necessarily show what will happen when the drug is used in humans.
No studies have been conducted to determine if nivolumab causes damage to genetic material
(DNA). Because nivolumab is an antibody, the risk of damage to DNA is believed to be low.
Laboratory and animal studies have not been conducted using nivolumab to determine if
nivolumab may cause cancer.
One program in monkeys has been conducted to evaluate the effects of nivolumab on pregnancy.
The preliminary findings revealed an increase in late stage pregnancy loss as well as deaths in
premature infants. These animal program findings suggest a potential risk to human pregnancy if
there is continued treatment with nivolumab during pregnancy. These abnormal findings [eg. late
stage pregnancy loss in monkeys] occurred at doses that are 9 times greater than the human
nivolumab dose of 3 mg/kg every 2 weeks used in this clinical trial.
8D. Human Pregnancy Outcomes
The use of nivolumab in pregnant women has not been formally studied in clinical studies.
One case has been identified of a nivolumab treated male patient with a female partner who
became pregnant. The pregnancy was uneventful, and at birth, the infant was slightly
underweight.
8E. Findings with Similar Drugs in the Class
Please ask your program doctor, pharmacist or other member of your doctor’s team for
information on similar drugs within this class.
8F. Significant Findings with Comparator Drugs
Not applicable.
8G. Use of a Program-Prohibited Contraceptive Method
Your program doctor will discuss prohibited and acceptable birth control methods for use during
your participation in this program.
Any birth control method used must be highly effective with a failure rate less than 1% per year
and must be discussed with your doctor if it is started during the course of the program.
At a minimum, patients must agree to the use of 2 methods of contraception, with one method
being highly effective and the other method being either highly effective or less effective as listed
below:
HIGHLY EFFECTIVE METHODS OF CONTRACEPTION
•
•
Male condoms with spermicide
Hormonal methods of contraception including combined oral contraceptive pills, vaginal
ring, injectables, implants, and intrauterine devices (IUDs) such as Mirena® by women
patients of child bearing potential (WOCBP) or male patient’s WOCBP partner. Female
partners of male patients participating in the program may use hormone-based
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(NIVOLUMAB, RENAL CELL CARCINOMA)
contraceptives as one of the acceptable methods of contraception since they will not be
receiving the program drug.
•
Non-hormonal IUDs, such as ParaGard®
•
Tubal ligation
•
Vasectomy
•
Complete abstinence
NOTE: Complete abstinence is defined as complete avoidance of heterosexual intercourse
and is an acceptable form of contraception for all program drugs. Patients who choose
complete abstinence are not required to use a second method of contraception, but female
patients must continue to have pregnancy tests. Acceptable alternate methods of highly
effective contraception must be discussed in the event that the patient chooses to forego
complete abstinence.
LESS EFFECTIVE METHODS OF CONTRACEPTION
•
Diaphragm with spermicide
•
Cervical cap with spermicide
•
Vaginal sponge
•
Male condom without spermicide
•
Progesterone only pills by a WOCBP patient or male patient’s WOCBP partner
•
Female condom
NOTE: A male and female condom must not be used together.
You should notify your program doctor if your method of contraception changes during the course
of this program.
8H. Requirements for Pregnancy Testing
If you are a woman of childbearing potential, you will have a pregnancy test within 24 hours of
your first dose of program medication, and then every 4 weeks while receiving the program drug,
and every 4 weeks or more frequently if required by the local standard of care for 23 weeks
following the end of treatment or early discontinuation of the program drug. Pregnancy testing
may be performed at home if an in-office visit is otherwise not required. Telephone contacts are
required to obtain results for all patients who perform pregnancy testing at home after they have
stopped the program drug treatment. Any positive results must be confirmed by serum pregnancy
testing at the program clinic site.
8I. Occurrence of Pregnancy or Suspected Pregnancy
If you become pregnant, suspect pregnancy, missed your period or it is late, or have a change in
your usual menstrual cycle (eg, heavier bleeding during your period or bleeding between
periods), you should immediately contact your program doctor.
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BMS INFORMED CONSENT FORM (ICF) FOR EARLY ACCESS TO MEDICINE
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8J. Discontinuation from the Program
Should you become pregnant during this program, you will immediately have the program
medication permanently discontinued and be referred for obstetric care. You will continue to be
followed for any side effects of the program treatment, provided it is safe for you and your unborn
baby to do so. Your doctor will discuss this with you, as well as options for additional appropriate
care for your cancer. Bristol-Myers Squibb has not set aside any funds to pay for any aspects of
obstetric, child or related care and does not plan to pay for them.
8K. Pregnancy Reporting
In case of a pregnancy, your pregnancy and its outcome will be reported to Bristol-Myers Squibb.
8L. Information for Men with Partners of Childbearing Potential
Most program drugs do not pose a risk to a woman who becomes pregnant while her male
partner is a program patient.
You are asked to inform your program doctor if your partner becomes pregnant while you are
enrolled in this program. You and your partner will be asked to provide information about the
pregnancy outcome. Bristol-Myers Squibb has not set aside any funds to pay for any aspects of
obstetric, child or related care and does not plan to pay for them.
8M. Complete Abstinence
Complete abstinence is defined as the complete avoidance of heterosexual intercourse.
Complete abstinence is an acceptable form of contraception and must be used throughout the
duration of the program and for the duration of time as specified under Section 8A. It is not
necessary to use a second method of contraception when abstinence is elected. Women of child
bearing potential who choose complete abstinence must continue to have pregnancy tests as
specified in Section 8H.
9)
Benefits
It is not possible to predict whether or not you will receive any personal benefit as a result of the
treatment given in this program.
Nivolumab may or may not lead to improvement of your renal cancer.
10) Alternative Treatment
Your doctor can provide detailed information about your cancer and the benefits of other treatments
that are available to you. You are encouraged to discuss treatment options with your doctor.
11)
Compensation for Injury
If you are injured during your participation in this program, you should contact the program doctor as
soon as possible in person or on the telephone number listed on page 1 of this consent form. Medical
care may be obtained in the same way you would ordinarily obtain other medical treatment.
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BMS INFORMED CONSENT FORM (ICF) FOR EARLY ACCESS TO MEDICINE
(NIVOLUMAB, RENAL CELL CARCINOMA)
A program-related injury is a physical injury that is directly caused by the program drug given as
described in the program guidance document or by medical procedures that are required by the
program and that are not standard of care.
A program-related injury does not include injuries directly caused by any of the following:

The natural course of your underlying disease or medical condition

Not following the instructions provided in this consent form or by program staff
Bristol-Myers Squibb shall not provide any compensation for any injuries related to this early access
to medicine scheme program.
12)
Any Prorated Payment
No compensation will be provided for your participation in this program.
13)
Any Anticipated Expenses
The NHS Trust that is taking part in this program will cover the costs of your care whilst you are on
this program. This includes routine laboratory blood tests, x-rays, MRIs, CT scans, and routine
medical care. If you have private medical insurance, you should check with the insurance provider
before agreeing to take part in this program to ensure that participating in this program will not affect
your medical insurance coverage.
You and/or your treating NHS Trust will not be charged for the cost of nivolumab.
Bristol-Myers Squibb is providing nivolumab free of charge up to the time when it is reimbursed for
use in the NHS in this setting or for maximum of one year from the date of approval by the European
Medicine Agency (EMA), whichever comes sooner.
14)
Voluntary Participation / Discontinuation of Treatment or Withdrawal of Consent
Your participation in this program is entirely voluntary. It is up to you to decide to take part or not. If
you do decide to take part, you are free to discontinue treatment or withdraw consent from the
program at any time without giving a reason. This will not affect your future medical care in any way.
Any information collected before your withdraw will be kept and used to complete the program.
Bristol-Myers Squibb may terminate the program at any time.
15)
Program Sponsor
Your doctor and/or the institution where you will be receiving the program drug will be the sponsor of
this program.
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16)
Confidentiality, Collection and Use of Program Data
16A. Collection of Program Data
Your program doctor and program staff will collect information about you which is relevant to this
program, specifically, information about your age, gender, condition for which the product is being
used for and details of the initial biopsy which was taken at diagnosis, the dose of nivolumab to be
given and how many doses are received, your fitness status, any health problem(s) you may have at
the of your entry into the program and other medications you are also taking. In addition, information
on year of birth and patients’ initial will also be collected in order to assign unique EAMS ID numbers
to be used to identify patients. This collected information about you is called “Data” in this document.
16B. Confidentiality and use of Program Data
Your Data will be used within this program and will be shared with the Scientific Opinion Holder
Bristol-Myers Squibb Pharmaceutical Limited, to produced regular safety reports to the UK Health
Authority (MHRA). Unless you decide otherwise, your Data may be further used by Bristol-Myers
Squibb Pharmaceutical Limited to analyze and understand the safety profile of patients.
You do have the right to access, rectify and object to processing of you Data in accordance with
the UK Data Protection Act (1988) by contacting your program doctor.
17)
Questions/Information




If you or your representative(s) have any questions regarding this program or in case of
program-related injuries, you should contact your program doctor on the telephone number
given on page one of this form.
If you or your representative(s) have any questions regarding your patient rights as they relate
to this program, you should contact your program doctor.
If you seek emergency care or are admitted to the hospital, please inform the treating doctor
that you are receiving treatment with an investigational drug and show them your Patient Alert
Card.
If any new information becomes available during the course of this program that may change
your willingness to participate, you will be informed.
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18) SIGNATURE




I have read and understand the information presented in this Informed Consent Form. I have
been given the opportunity to ask questions and all my questions have been answered.
I shall receive a signed and dated copy of this Informed Consent Form.
Please tick one of the boxes below:
 I agree that the program doctor may tell my personal doctor that I am taking part in this
program.
 I do not want the program doctor to tell my personal doctor that I am taking part in this
program.
I FREELY ACCEPT TO PARTICIPATE IN THIS PROGRAM
To be signed simultaneously, (i.e. on the same date), by all parties:
__________________________
____________________
_______________________________
Print Name of Patient
Date (to be entered by
Patient)
Signature
____________________________
____________________
_______________________________
Print Name of person obtaining the
consent
Date
Signature
Distribution: original for Program Doctor, signed copy to Patient
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BMS INFORMED CONSENT FORM (ICF) FOR EARLY ACCESS TO MEDICINE
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For programs that may include special populations (eg, mentally incapacitated, illiterate persons) the following
additional signature lines should be provided as appropriate to the patient population.
If the participant (or, if applicable, the legally acceptable representative) is unable to read the ICF, then the
signature of an impartial witness is needed. An impartial witness is a person who is independent of the program
and who is not influenced by the program staff or people involved with the program. The impartial witness must
attend the entire informed consent process and read the informed consent document and any other written
information.
The information in this informed consent document was read to the patient or his/her legally acceptable
representative. I believe he/she understands what was read and explained and is freely agreeing to participate
in the program. The patient has signed or made his/her mark on the signature line above.
Name of Impartial Witness
Date
(to be entered by witness)
Signature
For situations in which consent of an adult patient cannot be obtained (eg. emergency situations, dementia),
the signature of a legally acceptable representative is required:
Name of Patient’s legally acceptable
representative
____________________________
Date
(to be entered by Patient’s
legally acceptable
representative
Signature
State relationship to the patient
At any given time an incapacitated individual may explicitly refuse to participate in or request to be withdrawn
from the program. The program doctor must respect the request.
If protocol provides for interim signatory when a legally acceptable representative is not immediately available,
refer to ICH Section 4.8.15 and provide additional signatory text box, with the following text below it:
Where possible, the patient will be informed as soon as possible and his/her consent will be requested for the
continuation of the program.
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