Radiation Therapy Oncology Group

RADIATION THERAPY ONCOLOGY GROUP/
AMERICAN COLLEGE OF RADIOLOGY IMAGING NETWOR

RTOG 0837/ACRIN 6689

Informed Consent Template for Cancer Treatment Trials

(English Language Inclusive of Advanced Imaging Sub-Study)

Randomized, Phase Il, Double-Blind, Placebo-Controlled Trial Of Conventional Chemoradiation And Adjuvant Temozolomide Plus Cediranib Versus Conventional Chemoradiation And Adjuvant Temozolomide Plus Placebo In Patients With Newly Diagnosed Glioblastoma

[LIMITED INSTITUTIONS: Potential participants at advanced imaging–qualified institutions must consent to the Advanced MR and [18F]FLT PET mandatory imaging scans with blood collections and sampling if the patient is imaging eligible. This Informed Consent Form Template contains the therapeutic and imaging components of the RTOG 0837 and ACRIN 6689 trial]

This is a clinical trial, a type of research study. Your study doctor will explain the clinical trial to you. Clinical trials include only people who choose to take part. Please take your time to make your decision about taking part. You may discuss your decision with your friends and family. You can also discuss it with your health care team. If you have any questions, you can ask your study doctor for more explanation.

You are being asked to take part in this study because you have a type of brain tumor known as a glioblastoma.

Why is this study being done?

Standard treatment for patients with glioblastoma is temozolomide plus radiation followed by temozolomide alone. The purpose of this study is to determine whether the addition of an experimental medication, cediranib, to standard treatment will improve the outcome of treatment. Cediranib is designed to attack the blood vessels in glioblastoma. The study will find out what effects, good or bad, cediranib has on your tumor. One way that your study doctors will find this out is by using advanced imaging technology, along with an investigational imaging agent. They will help the study doctors to see what is happening inside your body while you are taking the cediranib or a placebo.

In addition, this study will try to determine whether the response to cediranib and the overall outcome depend on whether or not the tumor contains a particular genetic material called the MGMT gene. The MGMT is a protein in the tumor that may make your tumor resistant to temozolomide. After you register for the study, a sample of your tumor tissue will be submitted to a central laboratory to confirm that your tumor is a glioblastoma and to see whether your tumor has the MGMT gene. If you agree to participate in the study, this information will be used to place you in one of the study arms in a way that makes sure that the number of patients with the MGMT gene is balanced in each group (stratification).

In a study investigating cediranib in patients with recurrent glioblastoma, cediranib did not improve time to disease progression compared with standard treatment for recurrent glioblastoma. However, cediranib remains investigational in patients with newly diagnosed glioblastoma and may improve outcome in patients whose disease was not previously treated.

How many people will take part in the study?

About 177 people will take part in this study. About 50 of those participants will participate in advanced imaging using MR (magnetic resonance) and PET/CT (positron emission tomography and computer tomography) with blood collection and sampling.

What will happen if I take part in this research study?

Before you begin the study …

You will need to have the following exams, tests or procedures to find out if you can be in the study. These exams, tests or procedures are part of regular cancer care and may be done even if you do not join the study. If you have had some of them recently, they may not need to be repeated. This will be up to your study doctor.

·  Physical and neurological examination

·  MRI

·  Blood tests

·  Urine test

·  Electrocardiogram (EKG)

These scans are not part of regular cancer care and are being done because you are in this study.

·  MR scans using advanced techniques and contrast imaging agents and blood collection prior to the scan

·  PET/CT using an investigational radiotracer called [18F]FLT; blood sampling will be done during these scan and you will need to have two (2) intravenous catheters—tubes used to access your veins—for these scans (one [1] placed in a vein in each arm)

During the study …

If the exams, tests and procedures show that you can be in the study, and you choose to take part, then you will need the following tests and procedures. They are part of regular cancer care.

·  Physical and neurological examinations. These will be done about every other week for the first 10 weeks of treatment and about every month during treatment thereafter

·  MRI scans. These will be done about every 2 months during treatment

·  Blood tests to measure blood counts, electrolyte levels, and liver function. These will be done about every week for the first 6 weeks of treatment and about every 2 to 3 weeks during treatment thereafter

You will need these tests and procedures to see how the study is affecting your body.

·  Blood tests to see how your thyroid and heart muscle are functioning .These will be done at Weeks 2 and 3 of the study. About 1/2 to 1 teaspoon of blood will be taken each time.

·  Urine tests to see how your kidney is functioning. These will be done at Weeks 2, 5, 7, 8, and 11 of the study. About 1 teaspoon of urine will be collected each time.

·  Electrocardiogram to check for possible changes in your heart rhythm. This will be done at Week 2 of the study.

You will have the following imaging and blood collection procedures during the course of the study. Your treating doctors and research team will do their best to limit the number of additional visits needed for you to complete the advanced MRI and PET scans.

·  Four (4) mandatory MRI scans using the contrast imaging agent called gadolinium. Some of these scans will be completed the same day as your standard imaging. At least one (1) scan will require an additional visit for you to be part of the ACRIN 6689 advanced imaging sub-study;

·  Three (3) MRI scans similar to those described above are optional;

·  Three (3) to four (4) mandatory PET scans using an investigational imaging agent called [18F]FLT; these may mean additional visits as part of the study;

·  Blood collection—taken prior to the every MRI scan, equaling less than 20 mL (two vials of blood) each time;

·  Blood sampling—blood taken three times during each PET scan, totaling 3 mL (less than three teaspoons) each time;

·  Intravenous (IV) catheters—tubes used to access your veins—one (1) to two (2) IV catheters, possibly one [1] placed in a vein in each arm, for the imaging agents and blood collection.

You will also be asked to complete a medication diary while you are receiving treatment; this will help document when you take your medication and any side effects you experience. You will be asked to bring this diary with you to each visit, so you and your study doctor can review it together.

When you enter the study, your study doctor will need to send the block of tumor tissue obtained at the time of your brain tumor surgery to a central pathology site. There, a pathologist will confirm that the tumor is a glioblastoma and will also determine whether there is adequate tumor tissue to perform the analysis for MGMT. If the tumor is not a glioblastoma and/or if the tissue is not adequate for performing the MGMT analysis, you will not be able to continue on the study.

If the central pathology review indicates that your tumor is a glioblastoma with adequate tissue to perform the MGMT analysis, you will be "randomized" into one of the study groups described below. Randomization means that you are put into a group by chance. A computer program will place you in one of the study groups. Neither you nor your study doctor can choose the group you will be in. You will have a 1 in 3 (33%) chance of being placed in group 1, and you will have a 2 in 3 (67%) chance of being placed in group 2.

The FLT agent used for PET imaging is an investigational agent. The advanced MRI scans are also investigational in that study doctors are still learning about how the image results can be best applied to help patients. The techniques themselves for the MRI and PET scans are proven effective. In other words, the study doctors know how to do the images well; they are not yet sure how the images will best be used.

If you are in group 1 (often called "Arm A"): (3/7/11)

You will receive the standard treatments for glioblastoma—radiation and oral temozolomide— plus an oral placebo medication. A placebo is an inactive pill that looks exactly like an active pill. In this trial, the placebo will look exactly like the cediranib pill that patients randomized to group 2 will receive.

You will receive the placebo continuously throughout your treatment with radiation and temozolomide as follows: You will first receive the placebo every day for 3 days. You will then receive radiation therapy once per day on Monday through Friday, for a total of 30 treatments, plus temozolomide every day for 42 days and placebo every day for 42 days.

When you have finished the radiation part of your treatment, you will stop taking the temozolomide for 28 days but will continue taking the placebo every day. After 28 days, you will continue the daily placebo and will re-start temozolomide for days 1 through 5 every 28 days. You will take the placebo and temozolomide in this way for up to 12 months.

Treatment will be on an outpatient basis.

If you are in group 2 (often called "Arm B"): (3/7/11)

You will receive the standard treatments for glioblastoma—radiation and oral temozolomide—plus the experimental medication, oral cediranib.

You will receive cediranib continuously throughout your treatment with radiation and temozolomide as follows: You will first receive cediranib every day for 3 days. You will then receive radiation therapy one per day on Monday through Friday, for a total of 30 treatments, plus temozolomide every day for 42 days and cediranib every day for 42 days.

When you have finished the radiation part of your treatment, you will stop taking the temozolomide for 28 days but will continue taking cediranib every day. After 28 days, you will continue taking daily cediranib and will re-start temozolomide for days 1 through 5 every 28 days. You will take cediranib and temozolomide in this way for up to 12 months.

Treatment will be on an outpatient basis.

This study will be “double blind.” This means that you and your study doctor will not know whether you are assigned to group 1 (standard treatment plus placebo) or group 2 (standard treatment plus cediranib).

Treatment Study Plan

Another way to find out what will happen to you during the study is to read the chart below. Start reading at the top and read down the list, following the lines and arrows.

Diagnosis/Suspected Brain Tumor

↓

Brain Tumor Surgery

↓

Tissue from surgery sent to central site for evaluation

↓

Randomized Treatment
(You will be in one group or the other)

↓ ↓

Group 1
Oral placebo daily for 3 days
↓
Radiation therapy, Monday through Friday, for 30 treatments
+
Oral temozolomide daily for 42 days
+
Oral placebo daily for 42 days
↓
Oral placebo daily for 28 days
↓
Oral temozolomide daily on days 1 through 5 every 28 days for up to 12 cycles (48 weeks; 1 cycle = 28 days = 4 weeks)
+
Oral placebo daily for up to 12 cycles (48 weeks; 1 cycle = 28 days = 4 weeks) / Group 2
Oral cediranib daily for 3 days
↓
Radiation therapy, Monday through Friday, for 30 treatments
+
Oral temozolomide daily for 42 days
+
Oral cediranib daily for 42 days
↓
Oral cediranib daily for 28 days
↓
Oral temozolomide daily on days 1 through 5 every 28 days for up to 12 cycles (48 weeks; 1 cycle = 28 days = 4 weeks)
+
Oral cediranib daily for up to 12 cycles (48 weeks; 1 cycle = 28 days = 4 weeks)

When you are finished taking the study treatment…

You will be followed at regular check-ups, including MRI scans, every 3 months after completing treatment for the first year, then every 4 months for the second year, and then every 6 months thereafter.

About Advanced Imaging in the Study

Researchers hope that the advanced imaging using MRI and PET will help them learn more about how blood is supplied to the cancer and what is happening inside your body while you are taking the cediranib or a placebo. The advanced MRI will take more time to complete than the regular MRI examinations (each examination takes between 45 and 60 minutes). Blood will be collected prior to each of the MRI examinations. The PET imaging includes an investigational agent called FLT and blood samples collection. Your doctors will do their best to perform the PET scans on the same days as you receive your MR examinations.

Your study doctors hope that the blood collected during the trial will tell them more about how the study treatments and the FLT used for the PET scan react in the body. In the future, it is hoped the MRI and FLT PET scans performed before and after the start of chemotherapy treatment will allow doctors to tell in advance whether the tumor will respond well to treatment. Several studies using MRI and FLT PET at other institutions have shown promising results.