Irinotecan Plus Lenalidomide in Adult Patients With Recurrent Glioblastoma Multiforme: Phase I

Malignant Gliomas Clinical Trial

Official title: Phase I Trial of Irinotecan Plus Lenalidomide in Adult Patients With Recurrent Glioblastoma Multiforme

Status Terminated

Clinical Trial Summary

The goal of this clinical research study is to find the highest tolerable dose of lenalidomide combined with Camptosar (irinotecan) as well as to see if this drug combination can help control malignant gliomas.

Researchers will also study if a special magnetic resonance imaging (MRI) technique (dynamic MRI scan) is useful in looking at the effect of treatment on the tumor. Another goal is to learn the effect of lenalidomide on tumor tissue in patients who need surgery for the disease.

Clinical Trial Description

Lenalidomide is designed to change the body's immune system. It may also interfere with the development of tiny blood vessels that help support tumor growth. Therefore, in theory, it may decrease or prevent the growth of cancer cells.

Irinotecan is designed to stop cancer cells from dividing by causing "breaks" in the tumor cell DNA (the genetic material of cells), which may cause the cancer cells to die.

There are 2 parts to this study. In the first part (Phase I) of this study, researchers will try to find the highest tolerable dose of the study drug combination. In the second part (Phase II) of this study (after the highest tolerable dose is reached), researchers will try to learn the effectiveness of the study drug combination. If you are found to be eligible to take part in this study, you will be enrolled in Phase I or Phase II depending on which part is open at the time.

Phase I:

For this phase, you will be enrolled in a group of at least 3 participants to begin receiving lenalidomide and irinotecan. The dose of the study drug combination you receive will depend on when you enrolled in this study. At each dose level, if no intolerable side effects occur (after 4 weeks), the next 3 participants will be enrolled to receive a higher dose of the study drug combination. This process will continue until the highest tolerable dose of the study drug combination is reached. You will remain on the same dose throughout this study.

You will take lenalidomide by mouth (capsules) every morning on Days 1-21 of each 28 day cycle. Swallow lenalidomide capsules whole with water at the same time each day. Do not break, chew or open the capsules. In addition, you will also receive 1 additional dose of lenalidomide by mouth before the beginning of Cycle 1 (on Day 0 of Cycle 1).

If you miss a dose of lenalidomide, take it as soon as you remember on the same day. If you miss taking your dose for the entire day, take your regular dose the next scheduled day (do NOT take double your regular dose to make up for the missed dose). If you take too much lenalidomide or overdose, call your study doctor or health care provider or poison control center right away.

You will receive irinotecan by vein over 90 minutes once every 2 weeks (on Days 1 and 15). One cycle of treatment is 28 days long. You will have a "rest" period on Days 22-28 where you will not receive any study treatment.

Phase II:

For this phase, you will take lenalidomide by mouth (capsules) every morning on Days 1-21. Swallow lenalidomide capsules whole with water at the same time each day. Do not break, chew or open the capsules.

If you miss a dose of lenalidomide, take it as soon as you remember on the same day. If you miss taking your dose for the entire day, take your regular dose the next scheduled day (do NOT take double your regular dose to make up for the missed dose). If you take too much lenalidomide or overdose, call your study doctor or health care provider or poison control center right away.

You will receive irinotecan by vein over 90 minutes once every 2 weeks on Days 1 and 15. One cycle of treatment is 28 days long. You will have a "rest" period on Days 22-28 where you will not receive any study treatment.

Some participants in the Phase II study may also qualify for a component (a subset) of this study that will enroll up to 10 participants who will be undergoing surgical resection (removal of all or part of tissue) of the tumor. If the MRI scan (done during screening) shows that you have tumor regrowth and your doctor has recommended surgery to remove the regrown tumor, you will be eligible for this subset of the study.

For the subset, you will take lenalidomide (in the same manner as mentioned above), before surgery, for 3 days in a row with the last dose to be taken on the day of surgery.

Blood (about 2 teaspoons) will be drawn for pharmacokinetic (PK) testing on the first and second days that you take the study drug before surgery and on the day of surgery. PK testing measures the amount of study drug in the body at different time points.

Also, leftover tumor tissue (removed during your surgery) will be collected and used for testing to learn the effect of lenalidomide on your tumor tissue. The leftover tumor tissue samples will also be stored for research tissue/blood bank after the last participant completes the study. You will have a standard MRI scan and a dynamic MRI scan within 3 days after surgery.

Before your leftover tumor tissue samples can be used for research, the people doing the research must get specific approval from the Institutional Review Board (IRB) of M. D. Anderson. The IRB is a committee made up of doctors, researchers, and members of the community. The IRB is responsible for protecting the participants involved in research studies and making sure all research is done in a safe and ethical manner. All research done at M. D. Anderson, including research involving your leftover tumor tissue samples from this bank, must first be approved by the IRB.

All participants:

During treatment, you will have a complete physical exam and brain and spinal exam (performed by checking your coordination and strength by looking at how you walk and pull objects), which will be done every one cycle if you are in Phase I and every 2 cycles if you are in Phase II. On Day 1 of every cycle you will discuss birth control methods. You will have blood drawn (about 2 teaspoons each time) for routine tests once a week during Cycle 1 and then every 2 weeks in further cycles. You will have blood drawn (about 2 teaspoons each time) for routine tests on Day 15 of Cycle 1 and then on Day 1 in further cycles (every one cycle if you are in Phase I and every 2 cycles if you are in Phase II). You will also have a dynamic MRI scan done every 2 cycles after completion of Cycle 2. For all women who are able to have children: You will have a pregnancy test performed by your doctor within 10 - 14 days and 24 hours prior to starting lenalidomide therapy, even if you have not had any menses due to treatment of your disease or had as little as one menstrual period in the past 24 months. If you have regular or no menstrual cycles, you will have pregnancy tests every week for the first 28 days, then every 28 days while taking lenalidomide, when you stop taking lenalidomide, then 28 days after you have stopped taking lenalidomide. If you have irregular menstrual cycles, you will have pregnancy tests every week for the first 28 days, then every 14 days while taking lenalidomide, again when you have been taken off of lenalidomide therapy, and then 14 days and 28 days after you have stopped taking lenalidomide.

Treatment on this study will continue for at least 1 year, as long as the tumor does not grow back and there are no intolerable side effects. Treatment beyond 1 year will be based on whether the study doctor thinks that you may benefit without severe side effects.

If at any time during treatment the disease gets worse or you experience any intolerable side effects, you will be taken off this study, and your study doctor will discuss other treatment options with you.

Once you are completely off this study for any reason, you will have an end-of-study visit. During this visit, you will have a complete physical exam, including measurement of your height and weight. You will be asked how well you are able to perform the normal activities of daily living (performance status evaluation). You will have a brain and spinal exam. You will have blood drawn (about 5 teaspoons) for routine tests. This routine blood draw will include a pregnancy test for women who are able to have children. About 1 teaspoon of blood will be drawn to test for the ability of your blood to clot normally.

PK and Biomarker testing for Phase I:

If you are in Phase I, the following tests and procedures will be performed:

• Blood (about 1 teaspoon each time) will be drawn 6 times per day on Days 0, 1, and 4 of Cycle 1 for PK testing.

• Blood (about 1 teaspoon each time) will be drawn 3 times per day on Days 0, 1 and 4 of Cycle 1, and 1 time on Day 1 of Cycle 2 for biomarker testing. Biomarkers are chemical "markers" in the blood and/or tissue that may be related to your reaction to the study drug.

• If you experience a skin rash due to an intolerable dose of the study drug, a punch biopsy of your skin will be performed on a rash area of your body. This tissue will be used for testing to help the doctors understand what caused the serious reaction and for biomarker testing. To perform a punch biopsy, a hollow knife tool is used to remove a small coin-shaped sample of tissue.

This is an investigational study. Lenalidomide and irinotecan are FDA approved and commercially available for the treatment of some cancers. Their combination use is investigational and authorized for use in research only. Up to 51 patients will take part in this study. All will be enrolled at MD Anderson. ;

Related Conditions & MeSH terms

• Glioblastoma
• Glioma
• Malignant Gliomas

• NCT number: NCT00671801
• Study type: Interventional
• Source: M.D. Anderson Cancer Center
• Status: Terminated
• Phase: Phase 1
• Start date: April 29, 2008
• Completion date: February 2014