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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified October 2010 by Adnexus, A Bristol-Myers Squibb R&D Company.
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by:
Adnexus, A Bristol-Myers Squibb R&D Company
ClinicalTrials.gov Identifier:
NCT00768911
First received: October 7, 2008
Last updated: October 26, 2010
Last verified: October 2010
  Purpose

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


Condition Intervention Phase
Glioblastoma Multiforme
Drug: CT-322
Drug: Temozolomide
Procedure: Radiation Therapy
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 1, Open Label, Multi-Center Study To Evaluate The Safety And Tolerability of CT-322 Administered In Combination With Focal Brain Radiotherapy And Temozolomide To Subjects With Newly Diagnosed Glioblastoma Multiforme

Resource links provided by NLM:


Further study details as provided by Adnexus, A Bristol-Myers Squibb R&D Company:

Primary Outcome Measures:
  • Evaluate the safety and tolerability of CT-322 administered in combination with standard focal brain RT/TMZ to subjects with newly diagnosed GBM [ Time Frame: 15 ± 5 days post the last dose of study drug ] [ Designated as safety issue: Yes ]
  • Establish the recommended Phase 2 dose for the QW schedule of CT-322 for use in this combination [ Time Frame: Every 4 weeks until MTD or 2.0 mg/kg dose level is reached ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 [ Time Frame: Cycle 1, day 1 of RT phase of treatment ] [ Designated as safety issue: No ]
  • To describe the peak and trough concentrations of CT-322 when administered alone and when co-administered with TMZ [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • To evaluate the immunogenicity of CT-322 when administered in combination with standard focal brain RT/TMZ to subjects with newly diagnosed GBM [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: October 2008
Estimated Study Completion Date: June 2011
Estimated Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: CT-322

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

Drug: Temozolomide

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

Other Name: Temodar
Procedure: Radiation Therapy
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Informed consent
  • 18 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)
    • Total bilirubin ≤ 1.5 x ULN, unless due to Gilbert's disease
    • ALT and AST ≤ 3 x ULN
    • INR < 1.5 or PT within normal limits; and PTT within normal limits
    • Serum creatinine ≤ 1.5 x ULN
    • Urine protein/creatinine ratio (UPCR) < 1.0
    • Serum amylase and lipase ≤ 1.5 x the ULN
  • 2-dimensional echo or MUGA scan with LVEF within the institutional normal range
  • Stable or decreasing dose of corticosteroids for at least 1 week prior to screening MRI
  • Contraceptive measures for male and female participants for the duration of treatment and for 4 weeks following discontinuation of study treatment:

    --Female subjects having reproductive potential must have a negative serum pregnancy test within 72 hours before first administration of CT-322

  • Be able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures including receiving daily external beam RT in a radiation treatment facility:

    • integral to or affiliated with the investigative site and in which the treating radiation therapist is a participating study investigator; and
    • that has agreed to follow the radiation treatment guidance and complete the radiation treatment data collection forms

Exclusion Criteria:

  • 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
    • Glomerulonephritis or other protein-wasting glomerulopathy
  • Within 12 months before enrollment had:

    • Thrombotic or embolic cerebrovascular accident or transient ischemic attacks
    • CNS bleed (other than stable, grade 1)
    • Intraocular bleed, or any medical condition, which in the opinion of the investigator increases the risk for intra-ocular bleeding
    • Septic endocarditis (unless deemed cured and off all antibiotic therapy for at least 3 months)
    • Coronary artery bypass graft, angioplasty, vascular stenting, myocardial infarction, unstable angina; or
    • Symptomatic congestive heart failure (New York Heart Association ≥ class II)
  • Any intraparenchymal CNS hemorrhage at the time of enrollment except for:

    • Grade 1 intraparenchymal hemorrhage in the immediate post-operative period, or
    • Grade 1 intraparenchymal hemorrhage that has been stable (no significant change on 2 consecutive MRI scans at least 4 weeks apart) or improved
  • Subjects with a history of prior cardiotoxic chemotherapy exposure or subjects with thoracic irradiation involving cardiac tissue
  • Other, non-glioma related major surgery, open biopsy, or significant traumatic injury within 4 weeks before the first dose of CT-322

    --Placement of subcutaneous in-dwelling venous access port within 2 weeks before the first dose of CT-322

  • Known human immunodeficiency virus infection or known active acute or chronic viral hepatitis
  • Prior malignancy within the previous 3 years, except adequately treated basal cell skin cancer or cervical carcinoma in situ; or if the other primary malignancy is not currently clinically significant or requiring active intervention
  • Has any 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, in the judgment of the investigator, would make the subject inappropriate for entry in this study or non-compliant with study-related procedures
  • Subjects with medical conditions that would not permit, in the judgment of the investigator, the safe discontinuation of medications that are prohibited throughout the course of the study
  • Any condition requiring therapeutic anti-coagulation with either oral (e.g., warfarin type) or injectable anti-coagulants; however, low-dose (i.e., 1 mg daily [QD]) warfarin is permitted for venous port patency maintenance
  • Females who are pregnant or breast feeding.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00768911

Locations
United States, Arkansas
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States, 72205
United States, Illinois
University of Chicago Medical Center
Chicago, Illinois, United States, 60637
United States, Kentucky
University of Kentucky Hospital
Lexington, Kentucky, United States, 40536
United States, Missouri
Washington University Cancer Center
St. Louis, Missouri, United States, 63110
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
Sponsors and Collaborators
Adnexus, A Bristol-Myers Squibb R&D Company
  More Information

No publications provided

Responsible Party: Medical Director, Adnexus, A Bristol-Myers Squibb R&D Company, Adnexus, A Bristol-Myers Squibb R&D Company
ClinicalTrials.gov Identifier: NCT00768911     History of Changes
Other Study ID Numbers: CT-322.003
Study First Received: October 7, 2008
Last Updated: October 26, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by Adnexus, A Bristol-Myers Squibb R&D Company:
glioblastoma
Glioblastoma multiforme (newly diagnosed)

Additional relevant MeSH terms:
Glioblastoma
Astrocytoma
Glioma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Temozolomide
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014