CT-322 in Combination With Radiation Therapy and Temozolomide to Treat Newly Diagnosed Glioblastoma Multiforme

NCT00768911 | Unknown Phase 1

• 1 other identifier: CT-322.003
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 6

Brief Summary

Rationale: In light of the demonstrated activity of anti-angiogenesis agents in rGBM, it is reasonable to postulate that adding these agents to standard RT and chemotherapy in the up-front management of newly diagnosed GBM may improve the clinical benefit. This study will examine the safety and tolerability of adding CT-322 to the standard radiation therapy/temozolomide (RT/TMZ) backbone of treatment for newly diagnosed GBM

Conditions

Glioblastoma Multiforme

Keywords

glioblastoma; Glioblastoma multiforme (newly diagnosed)

Outcome Measures

Primary Outcomes (2)

• Evaluate the safety and tolerability of CT-322 administered in combination with standard focal brain RT/TMZ to subjects with newly diagnosed GBM

  15 ± 5 days post the last dose of study drug

• Establish the recommended Phase 2 dose for the QW schedule of CT-322 for use in this combination

  Every 4 weeks until MTD or 2.0 mg/kg dose level is reached

Secondary Outcomes (4)

• To describe the PK of TMZ and its active metabolite (MTIC) when TMZ is administered alone and when it is co-administered with CT-322 to a subset of approximately 12 subjects with newly diagnosed GBM

  Cycle 1, day 1 of RT phase of treatment

• To describe the peak and trough concentrations of CT-322 when administered alone and when co-administered with TMZ

  RT phase treatment weeks 1-3, 5, 7-10, day 1. Post RT phase cycles 1-3, day 1; then day 1 every 3 cycles thereafter; EOS visit

• To evaluate the immunogenicity of CT-322 when administered in combination with standard focal brain RT/TMZ to subjects with newly diagnosed GBM

  RT phase treatment weeks 1, 5, 7-8, day 1. Post RT phase cycles 1 and 3, day 1; then day 1 every 3 cycles thereafter; EOS visit

• To characterize the plasma biomarker response to CT-322 when administered in combination with standard focal brain RT/TMZ to subjects with newly diagnosed GBM

  RT phase treatment weeks 1-3, 5, 7-8, day 1. Post RT phase cycles 1-3, day 1, then day 1 every 3 cycles thereafter; EOS visit

Study Arms (1)

1

EXPERIMENTAL

Drug: CT-322; Drug: Temozolomide; Procedure: Radiation Therapy

Interventions

CT-322 DRUG

Intravenous solution, intravenous administration, starting dose level of 0.5 mg/kg/week Dose levels: 0.5 mg/kg/week, 1.0 mg/kg/week, 2.0 mg/kg/week

1

Temozolomide DRUG

75 mg/M2/day p.o. continuously 7 days per week during concurrent RT (max: 49 days) 150 mg/M2/day X 5 days; adjuvant cycle #1 200 mg/M2/day X 5 days; subsequent adjuvant cycles (# 2-12) if tolerability criteria met

Also known as: Temodar

1

Radiation Therapy PROCEDURE

RT will consist of fractionated focal irradiation administered using 2 Gy/fraction, QD x 5 days/week for 6 weeks, for a total dose of 60 Gy

1

Eligibility Criteria

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

You may qualify if:

• Informed consent
• years or older
• Newly diagnosed, histologically confirmed GBM (grade IV astrocytoma):
• Subjects will not be eligible if the original histology was a lower grade glioma and a subsequent histological diagnosis of a GBM is made
• Central independent pathology confirmation of GBM, concurrent with subject enrollment
• Subjects with sufficient biopsy material available to perform PCR analysis for MGMT promoter methylation must have tissue submitted to the designated laboratory for analysis. Subjects with insufficient tissue or indeterminate results will remain eligible for enrollment.
• KPS ≥ 60
• Be able to begin treatment with RT/TMZ within 6 weeks after biopsy or craniotomy with satisfactory wound healing prior to initiating treatment with CT-322
• Be able to undergo serial MRIs:
• Measurable or assessable disease may or may not be present
• CT scanning may not substitute for MRI scanning
• Have adequate bone marrow, liver, renal, and metabolic function as assessed by the following:
• Hemoglobin ≥ 10.0 g/dL (unsupported)
• Absolute neutrophil count (ANC) ≥ 1,500/mm3 (unsupported)
• Platelet count ≥ 100,000/mm3 (unsupported)

You may not qualify if:

• Prior CT-322 therapy or prior therapy with another VEGF-modulating agent (marketed or investigational) for malignant glioma
• History of hypersensitivity to TMZ or any of its excipients, or to Dacarbazine (DTIC)
• Prior treatment for GBM, except surgical resection and/or corticosteroid therapy
• Prior radiotherapeutic, or local (intra-tumoral) or systemic medical therapies (including but not limited to: chemotherapy, hormonal therapy, immunotherapy, anti-angiogenic therapy, implantable Gliadel® wafers, and molecularly targeted therapy) for brain tumors
• Current enrollment in another therapeutic clinical trial involving ongoing therapy
• Concurrent severe and/or uncontrolled medical disease that could compromise participation in the study such as:
• Pleural or pericardial effusion of ≥ grade 2
• Uncontrolled diabetes, despite optimal medical management, according to the opinion of the investigator
• Uncontrolled hypertension (defined as systolic blood pressure \> 150 mmHg or diastolic pressure \> 90 mmHg, despite optimal medical management)
• Any active craniotomy-related wound infection
• Active clinically significant infection (\> grade 2 by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events v3.0 (CTCAE) requiring the use of anti-microbial agents, or that would be otherwise, in the opinion of the investigator, interfere with the ability of the subject to participate
• History of clinically significant bleeding diathesis or coagulopathy including platelet function disorder (e.g., known hemophilia or von Willebrand disease) or acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies)
• Ongoing or recent (≤ 3 months) significant gastrointestinal bleeding untreated or recurring
• Untreated peptic ulcer disease or peptic ulcer disease treated for \< 3 months
• Non-healing wound (including craniotomy wound), ulcer, or bone fracture; or

Sponsors & Collaborators

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

Study Sites (6)

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

University of Kentucky Hospital

Lexington, Kentucky, 40536, United States

Location

Washington University Cancer Center

St Louis, Missouri, 63110, 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

MeSH Terms

Conditions

Glioblastoma

Interventions

CT-322; Temozolomide; Radiotherapy

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: October 7, 2008
• First Posted: October 8, 2008
• Study Start: October 1, 2008
• Primary Completion: October 1, 2010
• Study Completion: June 1, 2011
• Last Updated: October 27, 2010

Record last verified: 2010-10

Locations

US (6)