Gossypol (AT-101) and Temozolomide With or Without Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma Multiforme

NCT00390403 | Completed Phase 1

• 3 other identifiers: NABTT-0602 CDR0000507451U01CA062475NABTT-0602
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 8

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as gossypol and 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 kill tumor cells. Gossypol may help temozolomide work better by making tumor cells more sensitive to the drug. Gossypol may also make tumor cells more sensitive to radiation therapy. Giving gossypol and temozolomide together with radiation therapy may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of gossypol when given together with temozolomide with or without radiation therapy in treating patients with newly diagnosed glioblastoma multiforme.

Conditions

Brain and Central Nervous System Tumors

Keywords

adult glioblastoma; adult gliosarcoma; adult giant cell glioblastoma

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose

Secondary Outcomes (4)

• Toxicity

• Pharmacokinetic profile of gossypol

• Therapeutic activity

• Cellular and molecular outcomes (intratumoral expression levels of biomarkers, including Bcl-2 family protein expression [e.g., Bcl-2, Bcl-xL, MCl-1, Bax, Bak, BH3 domain], MGMT gene methylation status, and gene expression array)

Interventions

R-(-)-gossypol acetic acid DRUG

temozolomide DRUG

gene expression analysis GENETIC

mutation analysis GENETIC

protein expression analysis GENETIC

laboratory biomarker analysis OTHER

pharmacological study OTHER

adjuvant therapy PROCEDURE

radiation therapy RADIATION

Eligibility Criteria

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

DISEASE CHARACTERISTICS: * Histologically confirmed supratentorial grade IV astrocytoma (glioblastoma multiforme) * Meets 1 of the following criteria: * Completed surgery within the past 6 weeks (group I) * Received radiotherapy and concomitant temozolomide at least 4 weeks but no more than 7 weeks prior to start of study treatment (group II) * Must be on a stable corticosteroid regimen (no increase for 5 days) PATIENT CHARACTERISTICS: * Karnofsky performance status 60-100% * Hemoglobin ≥ 10 g/dL * Absolute neutrophil count ≥ 1,500/mm³ * Platelet count ≥ 100,000/mm³ * Creatinine ≤1.5 mg/dL * Bilirubin ≤ 1.5 mg/dL * ALT and AST ≤ 2.5 times upper limit of normal * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for 2 months after completion of study treatment * Mini Mental State Exam score ≥ 15 * Must be able to swallow and retain oral medication * No serious concurrent infection or medical illness that would preclude study participation * No other malignancy within the past 5 years, except for curatively treated carcinoma in situ or basal cell carcinoma of the skin * No sensory neuropathy ≥ grade 2 * No allergies to gossypol * No symptomatic hypercalcemia or hypercalcemia \> grade 2 * No gastrointestinal disease including any of the following: * Malabsorption syndrome * Disease significantly affecting gastrointestinal function * Ulcerative colitis * Inflammatory bowel disease * Partial or complete small bowel obstruction PRIOR CONCURRENT THERAPY: * See Disease Characteristics * Recovered from the immediate postoperative period * No prior radiotherapy, chemotherapy, immunotherapy, therapy with biologic agents (including immunotoxins, immunoconjugates, antisense agents, peptide-receptor antagonists, interferons, interleukins, tumor-infiltrating lymphocyte therapy, lymphokine-activated killer cells or gene therapy), or hormonal therapy for this brain tumor (group I) * Prior glucocorticoid therapy allowed * No prior polifeprosan 20 with carmustine implant (Gliadel wafers) (group I) * No prior gossypol * No prior radiosurgery or brachytherapy * No prior resection of the stomach or small intestine * No other concurrent anticancer therapy (i.e., chemotherapeutics or investigational agents) * No concurrent cytochrome p450 enzyme-inducing anticonvulsant drugs * No concurrent prophylactic filgrastim (G-CSF) * No concurrent iron supplements * Nutritional supplements containing iron allowed * No concurrent intensity-modulated radiotherapy * No concurrent electron, particle, implant, or stereotactic radiosurgery boost

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• National Cancer Institute (NCI): collaborator

Study Sites (8)

Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham

Birmingham, Alabama, 35294, United States

Location

H. Lee Moffitt Cancer Center and Research Institute at University of South Florida

Tampa, Florida, 33612-9497, United States

Location

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

Location

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231-2410, United States

Location

Josephine Ford Cancer Center at Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Wake Forest University Comprehensive Cancer Center

Winston-Salem, North Carolina, 27157-1096, United States

Location

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, 44195, United States

Location

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104-4283, United States

Location

MeSH Terms

Conditions

Central Nervous System Neoplasms; Glioblastoma; Gliosarcoma

Interventions

Temozolomide; Gene Expression Profiling; Chemotherapy, Adjuvant; Radiotherapy

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Genetic Techniques; Investigative Techniques; Combined Modality Therapy; Therapeutics; Drug Therapy

Study Officials

• John Fiveash, MD

  University of Alabama at Birmingham

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 18, 2006
• First Posted: October 19, 2006
• Study Start: February 1, 2007
• Primary Completion: June 1, 2009
• Last Updated: May 3, 2012

Record last verified: 2012-05

Locations

US (8)