Irinotecan Plus Lenalidomide in Adult Patients With Recurrent Glioblastoma Multiforme (Phase II)

Malignant Gliomas Clinical Trial

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

Status Withdrawn

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.

This record represents the Phase II portion of original Phase I/II study (see registration record NCT00671801).

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 found to be eligible to take part in this study, participant will be enrolled in Phase I or Phase II depending on which part is open at the time. (This record represents the Phase II portion of the study that was terminated prior to progressing to Phase II)

Phase I:

For this phase, participant will be enrolled in a group of at least 3 participants to begin receiving lenalidomide and irinotecan. The dose of the study drug combination received will depend on when participant 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. Participant will remain on the same dose throughout this study.

Participant 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, they will also receive 1 additional dose of lenalidomide by mouth before the beginning of Cycle 1 (on Day 0 of Cycle 1).

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

Participant 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. They will have a "rest" period on Days 22-28 where they will not receive any study treatment.

Phase II:

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

They 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. They will have a "rest" period on Days 22-28 where they 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 they have tumor regrowth and their doctor has recommended surgery to remove the regrown tumor, they will be eligible for this subset of the study.

For the subset, they 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 they 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 surgery) will be collected and used for testing to learn the effect of lenalidomide on their tumor tissue. The leftover tumor tissue samples will also be stored for research tissue/blood bank after the last participant completes the study. Participant will have a standard MRI scan and a dynamic MRI scan within 3 days after surgery.

All participants:

During treatment, participant will have a complete physical exam and brain and spinal exam (performed by checking coordination and strength by looking at how they walk and pull objects), which will be done every one cycle if they are in Phase I and every 2 cycles if they are in Phase II. On Day 1 of every cycle participant will discuss birth control methods. They 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. They 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 they are in Phase I and every 2 cycles if they are in Phase II). They 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: They will have a pregnancy test performed by a doctor within 10 - 14 days and 24 hours prior to starting lenalidomide therapy, even if they have not had any menses due to treatment of their disease or had as little as one menstrual period in the past 24 months. If they have regular or no menstrual cycles, they will have pregnancy tests every week for the first 28 days, then every 28 days while taking lenalidomide, when they stop taking lenalidomide, then 28 days after having stopped taking lenalidomide. If they have irregular menstrual cycles, they will have pregnancy tests every week for the first 28 days, then every 14 days while taking lenalidomide, again when they have been taken off of lenalidomide therapy, and then 14 days and 28 days after having 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 it may benefit without severe side effects.

If at any time during treatment the disease gets worse or participant experiences any intolerable side effects, they will be taken off this study, and the study doctor will discuss other treatment options.

Once completely off this study for any reason, they will have an end-of-study visit. During this visit, they will have a complete physical exam, including measurement of their height and weight. They will be asked how well they are able to perform the normal activities of daily living (performance status evaluation). They will have a brain and spinal exam. they 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 their blood to clot normally.

PK and Biomarker testing for Phase I:

If they 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 their reaction to the study drug.

• If they experience a skin rash due to an intolerable dose of the study drug, a punch biopsy of their skin will be performed on a rash area of their 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. ;

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Glioblastoma
• Malignant Gliomas

• NCT number: NCT02369367
• Study type: Interventional
• Source: M.D. Anderson Cancer Center
• Status: Withdrawn
• Phase: Phase 2
• Start date: April 2008
• Completion date: February 2014