CT-322 in Treating Patients With Recurrent Glioblastoma Multiforme and Combination Therapy With Irinotecan

NCT00562419 | Unknown Phase 2

• 1 other identifier: CT-322.002
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 10

Brief Summary

RATIONALE: CT-322 may stop the growth of glioblastoma multiforme by blocking blood flow to the tumor. Drugs used in chemotherapy, such as irinotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving CT-322 together with irinotecan may kill more tumor cells. PURPOSE: This phase 2 trial is studying the side effects, tolerability, and efficacy of CT-322 when given alone and in combination with irinotecan to patients with glioblastoma multiforme.

Conditions

Brain and Central Nervous System Tumors; Recurrent Glioblastoma Multiforme

Outcome Measures

Primary Outcomes (2)

• Safety and tolerability of CT-322 when administered alone or in combination with irinotecan hydrochloride (Part 1)

  15 ± 5 days post the last dose of study drug

• Progression-free survival at 6 months (Part 2)

  Measured upon initiation of cycles 2, 3, 5, 7, 9, 11, and end of study

Secondary Outcomes (3)

• To assess the plasma pharmacokinetics of CT-322 (Cmax, Tmax, AUC, T-HALF) derived from plasma concentration vs time for CT-322 given alone and in combination with irinotecan

  Part 1: cycle 1, days 1-3, day 5 or 6, days 8, 15, and 22; cycles 2-4, 6, 9, and 12, day 1; EOS and follow up visits. Part 2: cycle 1, days 1, 8, 15, and 22; cycles 2-4, 6, 9, and 12, day 1; EOS and follow up visits.

• To assess the presence of anti CT-322 antibodies

  Part 1: cycle 1, days 1 and 15; cycles 2-4, 6, 9, and 12, day 1; EOS and follow up visits. Part 2: cycle 1, days 1 and 15; cycles 2-4, 6, 9, and 12, day 1; EOS and follow up visits.

• To assess the biological activity of CT-322 as measured by plasma biological markers and neuroimaging

  Part 1: cycle 1, days 1, 2, 8, 15 and 22; cycles 2-4, 6, 9, and 12, day 1; EOS visit. Part 2: cycle 1, days 1, 8, 15 and 22; cycles 2-4, 6, 9, and 12 EOS visit.

Study Arms (2)

1

EXPERIMENTAL

CT-322

Drug: CT-322

2

EXPERIMENTAL

CT-322 and irinotecan hydrochloride

Drug: CT-322; Drug: irinotecan hydrochloride

Interventions

CT-322 DRUG

IV solution, weekly

1; 2

irinotecan hydrochloride DRUG

IV solution, biweekly

2

Eligibility Criteria

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

DISEASE CHARACTERISTICS * Histologically confirmed diagnosis of recurrent/progressive GBM presenting in first, second, or third relapse (progression following anti-cancer therapy other than surgery) * Bidimensionally measurable recurrent or residual primary disease on contrast-enhanced MRI PATIENT CHARACTERISTICS Age: • 18 and over Hematopoietic: * ANC ≥ 1,500/mL * Platelets ≥ 100,000/mL * Hemoglobin ≥ 9.0g/dL Hepatic: * AST and ALT ≤ 1.5 x ULN * Bilirubin ≤ 1.5 x ULN Coagulation: • INR \< 1.5 or PT within normal limits; and PTT within normal limits Renal: Creatinine ≤ 1.5 x ULN; Urine protein/creatinine ratio ≤ 1 Cardiovascular * 2-dimensional echocardiogram or cardiac multigated acquisition (MUGA) scan demonstrating left ventricular ejection fraction within the institutional normal range. * No coronary artery bypass graft, angioplasty, vascular stenting, myocardial infarction, unstable angina, congestive heart failure within the preceding 12 months. * No thrombotic or embolic cerebrovascular accident, including transient ischemic attacks within the past 12 months and no conditions that would not permit the safe discontinuation of specified anti-platelet medications * No intraparenchymal CNS hemorrhage, except for Grade 1 intraparenchymal hemorrhage in the immediate post-operative period or Grade 1 intraparenchymal hemorrhage that has been stable or improved Immunologic: • Not known to have human immunodeficiency virus infection (HIV) or active hepatitis B or C virus infection Other: * Negative pregnancy test within 72 hours prior to drug administration * Not pregnant or breast feeding * Fertile patients must agree to use effective methods of birth control and must agree to do so until at least 4 weeks after the last dose of drug administration * No serious non-healing wound, ulcer or bone fracture or recent significant traumatic injury (within 4 weeks) * Have ability to understand and sign an informed consent document * Be willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures * No other malignancy within the past 3 years, except for basal cell skin cancer, cervical carcinoma in situ, or other primary malignancy that is not currently clinically significant or does not require active intervention * No prior grade 3 or greater toxicity to irinotecan * No other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that could increase the risks associated with study participation or study drug administration or could interfere with the interpretation of the study results and would make the patient inappropriate for study entry PRIOR CONCURRENT THERAPY: Biologic therapy: * See Disease Characteristics * At least 4 weeks between prior biological or immunotherapy and recovered Chemotherapy: * See Disease Characteristics * At least 4 weeks since prior chemotherapy and recovered (6 weeks for nitrosoureas), unless there is unequivocal evidence of tumor progression Radiotherapy: • At least 12 weeks from completion of standard, daily radiotherapy and recovered, unless any of the following occurs: * New area of enhancement on MRI that is outside the radiotherapy field * Biopsy-proven recurrent tumor * Radiographic evidence of progressive tumor on 2 consecutive scans taken ≥ 4 weeks apart Surgery * At least 4 weeks since major surgery, open biopsy or significant traumatic injury and recovered * At least 1 week since other prior biopsy Other: * Not concurrently enrolled in another therapeutic clinical trial involving ongoing therapy * No prior treatment with VEGF or VEGFR inhibitors or vascular targeting/disrupting agents * No prior CT-322 therapy * No prior failure of irinotecan therapy * No prior treatment with stereotactic radiosurgery, brachytherapy, or a surgically created resection cavity to support other anatomically localized therapies * No severe or uncontrolled medical disease (uncontrolled diabetes, hypertension, serious infection \> CTCAE grade 2, significant bleeding or platelet dysfunction, gastrointestinal bleed)

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

Sponsors & Collaborators

• Adnexus, A Bristol-Myers Squibb R&D Company: lead

Study Sites (10)

University of California, San Diego

La Jolla, California, 92037-0845, United States

Location

University of Kentucky

Lexington, Kentucky, 40536, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02114, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

SUNY Upstate Medical University

Syracuse, New York, 13210, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Virgina

Charlottesville, Virginia, 22908, United States

Location

University of Wisconsin Hospital

Madison, Wisconsin, 53792, United States

Location

MeSH Terms

Conditions

Central Nervous System Neoplasms; Glioblastoma

Interventions

CT-322; Irinotecan

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)

Camptothecin; Alkaloids; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: November 20, 2007
• First Posted: November 22, 2007
• Study Start: October 1, 2007
• Primary Completion: June 1, 2011
• Study Completion: December 1, 2011
• Last Updated: October 27, 2010

Record last verified: 2010-10

Locations

US (10)