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

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

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.

Study Overview

• Status: Unknown
• Conditions: Brain and Central Nervous System Tumors; Recurrent Glioblastoma Multiforme
• Intervention / Treatment: Drug: CT-322; Drug: irinotecan hydrochloride

• Study Type: Interventional
• Enrollment (Anticipated): 72
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
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.

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Primary Completion (Anticipated): June 1, 2011
• Study Completion (Anticipated): December 1, 2011

Study Registration Dates

• First Submitted: November 20, 2007
• First Submitted That Met QC Criteria: November 20, 2007
• First Posted (Estimate): November 22, 2007

Study Record Updates

• Last Update Posted (Estimate): October 27, 2010
• Last Update Submitted That Met QC Criteria: October 26, 2010
• Last Verified: October 1, 2010

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Disease Attributes; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Recurrence; Nervous System Neoplasms; Central Nervous System Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Irinotecan
• Other Study ID Numbers: CT-322.002