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

Study Description

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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.

Condition or disease	Intervention/treatment	Phase
Brain and Central Nervous System Tumors; Recurrent Glioblastoma Multiforme	Drug: CT-322; Drug: irinotecan hydrochloride	Phase 2

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	72 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Phase 2, 2-Part, Multicenter, Open-Label Study to Evaluate the Safety, Tolerability, and Efficacy of CT-322 Monotherapy and Combination Therapy With Irinotecan in Patients With Recurrent Glioblastoma Multiforme
Study Start Date :	October 2007
Estimated Primary Completion Date :	June 2011
Estimated Study Completion Date :	December 2011

Arms and Interventions

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Arm	Intervention/treatment
Experimental: 1; CT-322	Drug: CT-322; IV solution, weekly
Experimental: 2; CT-322 and irinotecan hydrochloride	Drug: CT-322; IV solution, weekly; Drug: irinotecan hydrochloride; IV solution, biweekly

Outcome Measures

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Primary Outcome Measures :

1. Safety and tolerability of CT-322 when administered alone or in combination with irinotecan hydrochloride (Part 1) [ Time Frame: 15 ± 5 days post the last dose of study drug ]
2. Progression-free survival at 6 months (Part 2) [ Time Frame: Measured upon initiation of cycles 2, 3, 5, 7, 9, 11, and end of study ]

Secondary Outcome Measures :

1. 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 [ Time Frame: 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. ]
2. To assess the presence of anti CT-322 antibodies [ Time Frame: 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. ]
3. To assess the biological activity of CT-322 as measured by plasma biological markers and neuroimaging [ Time Frame: 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. ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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)

Contacts and Locations

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Locations

United States, California
University of California, San Diego
La Jolla, California, United States, 92037-0845
United States, Kentucky
University of Kentucky
Lexington, Kentucky, United States, 40536
United States, Massachusetts
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02114
United States, Michigan
Henry Ford Health System
Detroit, Michigan, United States, 48202
United States, New York
SUNY Upstate Medical University
Syracuse, New York, United States, 13210
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Rhode Island
Rhode Island Hospital
Providence, Rhode Island, United States, 02903
United States, Texas
MD Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Virginia
University of Virgina
Charlottesville, Virginia, United States, 22908
United States, Wisconsin
University of Wisconsin Hospital
Madison, Wisconsin, United States, 53792

Sponsors and Collaborators

Adnexus, A Bristol-Myers Squibb R&D Company

More Information

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Responsible Party:	Medical Director, Adnexus, A Bristol-Myers Squibb R&D Company, Adnexus, A Bristol-Myers Squibb R&D Company
ClinicalTrials.gov Identifier:	NCT00562419 History of Changes
Other Study ID Numbers:	CT-322.002
First Posted:	November 22, 2007
Last Update Posted:	October 27, 2010
Last Verified:	October 2010

Additional relevant MeSH terms:

Glioblastoma; Nervous System Neoplasms; Central Nervous System Neoplasms; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial	Neoplasms, Nerve Tissue; Neoplasms by Site; Nervous System Diseases; Irinotecan; Camptothecin; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Topoisomerase I Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action