Cilengitide, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma Multiforme

NCT00085254 | Completed Phase 1 Results DMC

• 4 other identifiers: NCI-2012-02932NABTT 0306CDR0000368451U01CA062475
• Study Type: interventional
• Target: 112
• Locations: 1 country
• Sites: 8

Brief Summary

Cilengitide may stop the growth of cancer by stopping blood flow to the tumor. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to damage tumor cells. Giving cilengitide together with temozolomide and radiation therapy may kill more tumor cells. This randomized phase I/II trial is studying the side effects and best dose of cilengitide when given together with temozolomide and radiation therapy and to compare how well they work in treating patients with newly diagnosed glioblastoma multiforme

Conditions

Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma

Outcome Measures

Primary Outcomes (3)

• Dose Limiting Toxicities of EMD + RT and TMZ

  pts will be evaluated from first dose through end of initiation cycle. (6 weeks of RT+TMZ +EMD and 4 weeks of EMD alone) to review dose limiting toxicity (DLT) using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (Phase I) DLT defined as: Known TMZ hematological toxicities will not be considered dose limiting. Nonhematological toxicities Grades 3-4 severity (except nausea and vomiting without sufficient antiemetic prophylaxis)

  10 weeks

• Maximum Tolerated or Tolerable Dose (MTD) - 3 Pre-defined Doses

  pts will be evaluated from first dose through end of initiation cycle. (6 weeks of RT+TMZ +EMD and 4 weeks of EMD alone) to review any dose limiting toxicity (DLT) using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (safety run-in) DLT defined as: Known TMZ hematological toxicities will not be considered dose limiting. cohorts at these 3 defined doses: 500mg, 1000mg and 2000mg MTD defined as: dose producing DLT in 2 out of 6 patients or dose level below the dose which produced DLT in \>/= 2 out of 3 patients, or in \>/= 3 out of 6 patients If no MTD (maximum tolerable dose) was defined through 3 steps of dose escalation, phase 2 will proceed with a randomized treatment allocation of the two pre-specified dosage arms: low dose; 500mg and high dose; 2000mg

  10 weeks

• Overall Survival (Phase II)

  The overall survival is calculated from time of histological diagnosis to death occurance - median based on all 112 patients, all dose levels

  up to 36 months

Secondary Outcomes (2)

• Overall Survival Based on Dose Level - Phase 2

  Up to 3 years

• Frequency of Hematologic and Nonhematologic Adverse Events

  Up to 1 year

Study Arms (3)

Arm 1 (Safety Run In)

EXPERIMENTAL

INITIATION COURSE: Patients receive cilengitide IV over 1 hour on days 1 and 4. Treatment repeats weekly for 10 weeks. Patients also receive oral temozolomide and undergo radiotherapy one hour later on days 1-5 of weeks 1-6. MAINTENANCE COURSES: Patients receive oral temozolomide once daily on days 1-5 in courses 1-6. Patients also receive cilengitide IV on days 1, 4, 8, 11, 15, 18, 22, and 25. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Doses of cilengitide: 500mg, 1000mg and 2000mg Temozolimide, Radiation Therapy, laboratory biomarker analysis, pharmacological study

Drug: cilengitide; Drug: temozolomide; Radiation: radiation therapy; Other: laboratory biomarker analysis; Other: pharmacological study

Phase II (Arm1-500mg)

EXPERIMENTAL

INITIATION COURSE: Patients receive cilengitide (500mg) IV over 1 hour on days 1 and 4. Treatment repeats weekly for 10 weeks. Patients also receive oral temozolomide and undergo radiotherapy one hour later on days 1-5 of weeks 1-6. MAINTENANCE COURSES: Patients receive oral temozolomide once daily on days 1-5 in courses 1-6. Patients also receive cilengitide IV (500mg) on days 1, 4, 8, 11, 15, 18, 22, and 25. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. cilengitide, Temozolimide, Radiation Therapy, laboratory biomarker analysis, pharmacological study

Drug: cilengitide; Drug: temozolomide; Radiation: radiation therapy; Other: laboratory biomarker analysis; Other: pharmacological study

Phase II (Arm 2 -2000mg)

EXPERIMENTAL

INITIATION COURSE: Patients receive cilengitide (2000mg) IV over 1 hour on days 1 and 4. Treatment repeats weekly for 10 weeks. Patients also receive oral temozolomide and undergo radiotherapy one hour later on days 1-5 of weeks 1-6. MAINTENANCE COURSES: Patients receive oral temozolomide once daily on days 1-5 in courses 1-6. Patients also receive cilengitide IV (2000mg) on days 1, 4, 8, 11, 15, 18, 22, and 25. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. cilengitide,Temozolimide, Radiation Therapy, laboratory biomarker analysis, pharmacological study

Drug: cilengitide; Drug: temozolomide; Radiation: radiation therapy; Other: laboratory biomarker analysis; Other: pharmacological study

Interventions

cilengitide DRUG

Given IV

Also known as: EMD 121974

Arm 1 (Safety Run In); Phase II (Arm 2 -2000mg); Phase II (Arm1-500mg)

temozolomide DRUG

Given orally

Also known as: SCH 52365, Temodal, Temodar, TMZ

Arm 1 (Safety Run In); Phase II (Arm 2 -2000mg); Phase II (Arm1-500mg)

radiation therapy RADIATION

Undergo radiotherapy

Also known as: irradiation, radiotherapy, therapy, radiation

Arm 1 (Safety Run In); Phase II (Arm 2 -2000mg); Phase II (Arm1-500mg)

laboratory biomarker analysis OTHER

Correlative studies

Arm 1 (Safety Run In); Phase II (Arm 2 -2000mg); Phase II (Arm1-500mg)

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Arm 1 (Safety Run In); Phase II (Arm 2 -2000mg); Phase II (Arm1-500mg)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically confirmed supratentorial grade IV astrocytoma (glioblastoma multiforme)
• Patients must not have received prior radiation therapy, chemotherapy, immunotherapy or therapy with biologic agent (including immunotoxins, immunoconjugates, antisense, peptide receptor antagonists, interferons, interleukins, TIL, LAK or gene therapy), or hormonal therapy for their brain tumor; glucocorticoid therapy is allowed
• Patients must have a Karnofsky performance status \>= 60% (i.e. the patient must be able to care for himself/herself with occasional help from others)
• Absolute neutrophil count \>= 1500/mm\^3
• Platelets \>= 100,000/mm\^3
• Creatinine =\< 1.5 mg/dl or creatinine clearance \>= 60 mL/min
• Total bilirubin =\< 1.5 mg/dl
• Transaminases =\< 4 times above the upper limits of the institutional normal
• Patients must be able to provide written informed consent
• Patients must have recovered from the immediate post-operative period and be maintained on a stable corticosteroid regimen (no increase for 5 days) prior to the start of treatment
• Patients with the potential for pregnancy or impregnating their partner must agree to follow acceptable birth control methods to avoid conception; women of childbearing potential must have a negative pregnancy test
• Patients must have a Mini Mental State Exam score of \>= 15
• Patients must have tumor tissue form completed and signed by a pathologist

You may not qualify if:

• Patients with serious concurrent infection or medical illness, which would jeopardize the ability of the patient to receive the treatment outlined in this protocol with reasonable safety
• Patients who are pregnant or breast-feeding
• Patients receiving concurrent therapy for their tumor (i.e. chemotherapeutics or investigational agents)
• Patients with a concurrent or prior malignancy are ineligible unless they are patients with curatively treated carcinoma-in-situ or basal cell carcinoma of the skin; patients who have been free of disease (any prior malignancy) for \>= five years are eligible for this study
• Patients who are unable to undergo an MRI evaluation
• Patients with a history of wound-healing disorders, advanced coronary disease, or with a recent history (# 1 year) of peptic ulcer disease are ineligible

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (8)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (1)

• Nabors LB, Mikkelsen T, Hegi ME, Ye X, Batchelor T, Lesser G, Peereboom D, Rosenfeld MR, Olsen J, Brem S, Fisher JD, Grossman SA; New Approaches to Brain Tumor Therapy (NABTT) Central Nervous System Consortium. A safety run-in and randomized phase 2 study of cilengitide combined with chemoradiation for newly diagnosed glioblastoma (NABTT 0306). Cancer. 2012 Nov 15;118(22):5601-7. doi: 10.1002/cncr.27585. Epub 2012 Apr 19.

  PMID: 22517399 RESULT

MeSH Terms

Conditions

Glioblastoma; Gliosarcoma

Interventions

Cilengitide; Temozolomide; Radiotherapy; Radiation

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Therapeutics; Physical Phenomena

Limitations and Caveats

Study is safety run-in / phase 2 study. Pre-defined doses in safety run-in, 500, 1000 \& 2000mg. Safety run-in is under an assumption of low probability of DLT with these dosages. NO actual MTD was defined in the safety run in, all doses were safe.

Results Point of Contact

• Title: Louis Burt Nabors, MD
• Organization: Adult Brain Tumor Consortium (ABTC)

bnabors@uab.edu

205-934-1432

Study Officials

• Louis Nabors, MD

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 10, 2004
• First Posted: June 11, 2004
• Study Start: April 1, 2005
• Primary Completion: November 1, 2012
• Study Completion: November 1, 2012
• Last Updated: February 25, 2016
• Results First Posted: February 25, 2016

Record last verified: 2015-10

Locations

US (8)