A Phase I Trial of Enzastaurin (LY317615) in Combination With Carboplatin in Adults With Recurrent Gliomas

Completed · Phase 1

Conditions studied: Recurrent Gliomas

In brief

This study will evaluate the safety and effectiveness of Enzastaurin, an experimental drug that may prevent the growth of tumor vessels, in combination with Carboplatin, for patients who have a glioma, a type of brain tumor. Carboplatin is used for treating many kinds of cancers, though not recurrent gliomas. Tumor growth involves new cancer cell formation and accumulation, requiring a blood supply. Research shows that brain tumor cells can produce substances that stimulate new blood vessel formation. This study will look into whether the combination of drugs can stop that process. Patients ages 18 and older who have recurring gliomas, who are not pregnant or breast feeding, and who do not have serious diseases may be eligible for this study. About 96 patients will participate for 1 year. They will have a physical examination, give blood and urine samples for analysis, and undergo magnetic resonance imaging (MRI) or computed tomography (CT) scans regarding tumor growth, and perhaps an electrocardiogram. Patients may also undergo a dynamic MRI with spectroscopy or PET scan (positron emission tomography), to distinguish a live tumor from a dying one. Researchers are studying patients taking a certain type of antiseizure medicine and patients who are not taking it because some antiseizure medicines may change the way the body handles a drug such as Enzastaurin. There will be two groups of participants, with 16 to 48 each. Group A is not taking enzyme-inducing antiseizure drugs, and Group B is taking such drugs. In Groups A and B are four dose levels, with 4 to12 patients at each level. Patients' doctors will tell them which group they belong to and how much Enzastaurin and Carboplatin they will take. Treatment consists of Enzastaurin every day for 5 weeks in Cycle 1 only and for 4 weeks beginning with Cycle 2 (each 4-week period as a cycle). Patients take Enzastaurin within 30 minutes after a meal. History, physical, and neurological examinations are repeated at the end of Cycle 1 and then every 4 weeks. Patients will have a repeat head MRI or CT scan before each cycle. If they tolerate the drugs without serious side effects and the tumor is not growing, they may continue with another cycle of Enzastaurin, taking the tablets every day, and Carboplatin being infused on Day 8 of Cycle 1 and on Day 1 of each additional cycle. Routine lab tests are done regularly. Patients will continue the 4-week cycles of treatment for as long as they have no serious side effects and there are no signs of tumor growth. Side effects of Enzastaurin may be fatigue, constipation, cough, and nausea. In men, there may be a decrease in sperm count. Carboplatin can lead to low counts in blood cells and platelets, and there may also be an allergic reaction. Vomiting is a likely side effect. At injection sites, there may be redness, swelling, and pain. This study may or may not have a direct benefit for participants. However, information gained may help the sponsor of the study, Eli Lilly and Company, and may help patients in the future who have gliomas.

Key facts

Study ID: NCT01445119
Run by: Eli Lilly and Company
People needed: 58
Starts: 2007-01-01
Expected to finish: 2013-07-01
Last updated by the study team: 2013-08-28

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may not qualify if…

Patients who, in the view of the treating physician, have significant active cardiac, hepatic, or renal diseases are ineligible.
No concurrent use of other standard chemotherapeutics or investigative agents.
Prior treatment with platinum-based therapy.
Patients known to have an allergic response to mannitol.
Patients known to have an active malignancy other than their malignant glioma (except non-melanoma skin cancer or carcinoma in-situ of the cervix).
Patients who have an active infection requiring IV antibiotics.
Patients who are pregnant or breast feeding.
Patients who have any disease that will obscure toxicity or dangerously alter drug metabolism.
QTc with Bazett's correction that is unmeasurable, or greater than or equal to 460 msec on screening ECG. If a patient has QTc greater than or equal to 460 msec on screening ECG, a second screen ECG may be repeated at least 24 hours apart. The average QTc from the 2 screening ECGs must be less than 460 msec in order for the patient to be eligible for the study.
EKG demonstrating clinically significant arrythmia (multifocal premature ventricular contraction [PVC], bigeminy, trigeminy, ventricular tachycardia, bradycardia) that is symptomatic or requires treatment (CTCAE Grade 3), or asymptomatic sustained ventricular tachycardia.
Patients who have baseline EKGs suggestive of past or present cardiac ischemia will not be eligible unless they have an appropriate (as defined by the P.I. of this trial) negative cardiac work up (that is, echocardiogram, stress test).
Patients may not be on systemic anti-coagulants (that is, heparin, warfarin, small heparin fragments).

Where it is running

National Institutes of Health Clinical Center, 9000 Rockville Pike — Bethesda, Maryland, United States

Full record on ClinicalTrials.gov

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