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ATN-161 and Carboplatin in Treating Patients With Recurrent Malignant Glioma

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ClinicalTrials.gov Identifier: NCT00352313
Recruitment Status : Completed
First Posted : July 14, 2006
Last Update Posted : May 2, 2012
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by:
National Institutes of Health Clinical Center (CC)

Brief Summary:

RATIONALE: ATN-161 may stop the growth of tumor cells by blocking blood flow to the tumor. Drugs used in chemotherapy, such as carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving ATN-161 together with carboplatin may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of ATN-161 when given together with carboplatin and to see how well they work in treating patients with recurrent malignant glioma.


Condition or disease Intervention/treatment Phase
Brain and Central Nervous System Tumors Drug: ATN-161 Drug: carboplatin Phase 1 Phase 2

Detailed Description:

OBJECTIVES:

Primary

  • Establish the safety of ATN-161 and carboplatin in patients with recurrent intracranial malignant glioma.
  • Determine the maximum tolerated dose of ATN-161 when administered with carboplatin in these patients. (phase I)
  • Determine the antitumor activity of ATN-161 when administered with carboplatin in these patients. (phase II)

Secondary

  • Describe the effects of this regimen on potential biomarkers of activity, including functional imaging with brain perfusion scans and circulating endothelial progenitor cells.
  • Obtain preliminary evidence of efficacy of this regimen in these patients. (phase I)
  • Characterize the plasma concentrations of this regimen in these patients. (phase I)

OUTLINE: This is an open-label, phase I dose-escalation study of ATN-161 followed by a phase II study. Patients in the phase II portion of the study are stratified according to tumor type (glioblastoma multiforme vs anaplastic glioma).

  • Phase I: Patients receive ATN-161 IV over 10 minutes 3 times weekly in weeks 1-6 and carboplatin IV over 20 minutes in week 3 during course 1. Beginning in course 2, patients receive carboplatin IV over 20 minutes in week 1 and ATN-161 IV over 10 minutes 3 times weekly in weeks 1-4. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of ATN-161 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity during the first 6 weeks of treatment.

  • Phase II: Patients receive carboplatin IV in week 1 and ATN-161 IV, at the MTD determined in phase I, 3 times weekly in weeks 1-4. Treatment repeats every 4 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Patients undergo blood collection at baseline and then periodically during phase I course 1 for pharmacokinetic and pharmacodynamic analysis and at baseline and then periodically during study for biomarker (e.g., circulating endothelial progenitor cells) correlative studies.

After completion of study treatment, patients are followed for 28 days.

PROJECTED ACCRUAL: A total of 82 patients will be accrued for this study.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 82 participants
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II Study of ATN-161 and Carboplatin in Adult Patients With Recurrent Intracranial Malignant Glioma
Study Start Date : May 2006
Actual Primary Completion Date : January 2007
Actual Study Completion Date : January 2008


Arm Intervention/treatment
Experimental: Phase I
Patients receive ATN-161 IV over 10 minutes 3 times weekly in weeks 1-6 and carboplatin IV over 20 minutes in week 3 during course 1. Beginning in course 2, patients receive carboplatin IV over 20 minutes in week 1 and ATN-161 IV over 10 minutes 3 times weekly in weeks 1-4. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.
Drug: ATN-161
Given IV

Drug: carboplatin
Given IV

Experimental: Phase II
Patients receive carboplatin IV in week 1 and ATN-161 IV, at the MTD determined in phase I, 3 times weekly in weeks 1-4. Treatment repeats every 4 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Drug: ATN-161
Given IV

Drug: carboplatin
Given IV




Primary Outcome Measures :
  1. Safety
  2. Maximum tolerated dose (phase I)
  3. Progression-free survival at 6 months
  4. Response rate (phase I)
  5. Overall survival

Secondary Outcome Measures :
  1. Efficacy
  2. Response rate (phase II)


Information from the National Library of Medicine

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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 intracranial malignant glioma

    • Original low-grade glioma histology allowed provided there is subsequent histologic confirmation of malignant glioma
  • Any of the following diagnoses:

    • Glioblastoma multiforme
    • Gliosarcoma
    • Anaplastic astrocytoma
    • Anaplastic oligodendroglioma
    • Anaplastic mixed oligoastrocytoma
    • Malignant astrocytoma not otherwise specified
  • Recurrent disease

    • Must have failed prior radiotherapy

      • Must have confirmation of true progressive disease (rather than radiation necrosis) based upon either positron emission tomography or thallium scanning, MR spectroscopy, or surgical documentation of disease if radiographic recurrence is within the high-dose radiation field (for patients who underwent prior interstitial brachytherapy or stereotactic radiosurgery)
  • Prior recent resection of recurrent or progressive tumors allowed if all of the following criteria are met:

    • Recovered from prior surgery
    • Evaluable disease after resection
  • Unequivocal evidence of tumor progression by MRI

    • Steroid dose must be stable for ≥ 5 days prior to MRI

PATIENT CHARACTERISTICS:

  • Karnofsky performance status 60-100%
  • Life expectancy > 8 weeks
  • WBC ≥ 3,000/mm³
  • Absolute neutrophil count ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Hemoglobin ≥ 10 g/dL (transfusion allowed)
  • AST < 2.5 times upper limit of normal (ULN)
  • Bilirubin < 2.5 times ULN
  • Creatinine < 1.5 mg/dL OR creatinine clearance ≥ 60 mL/min
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 1 month after completion of study treatment
  • No significant medical illness that would preclude study treatment
  • No history of other cancer (except nonmelanoma skin cancer or carcinoma in situ of the cervix) unless disease is in complete remission and off all therapy for ≥ 1 year
  • No active infection or serious intercurrent medical illness
  • No disease that will obscure toxicity or dangerously alter drug metabolism
  • Able to undergo MRI scan and receive contrast agents for perfusion scanning

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • Recovered from prior therapy
  • At least 28 days since prior cytotoxic therapy
  • At least 14 days since prior vincristine
  • At least 42 days since prior nitrosoureas
  • At least 21 days since prior procarbazine
  • At least 7 days since prior interferon, tamoxifen, thalidomide, isotretinoin, or other noncytotoxic agents (radiosensitizer does not count)
  • At least 14 days since prior noncytotoxic investigational agents
  • At least 42 days since prior radiotherapy
  • No prior cisplatin, carboplatin, oxaliplatin, or platinum-containing analogue
  • No concurrent prophylactic filgrastim (G-CSF) or sargramostim (GM-CSF)
  • No other concurrent anticancer therapy (including chemotherapy, radiotherapy, hormonal therapy, or immunotherapy)
  • No other concurrent investigational drugs

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00352313


Locations
United States, Maryland
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
Bethesda, Maryland, United States, 20892-1182
Sponsors and Collaborators
National Institutes of Health Clinical Center (CC)
National Cancer Institute (NCI)
Investigators
Principal Investigator: Howard A. Fine, MD NCI - Neuro-Oncology Branch

ClinicalTrials.gov Identifier: NCT00352313     History of Changes
Obsolete Identifiers: NCT00340041
Other Study ID Numbers: 060170
06-C-0170
NCI-P6790
ATN-161-002
CDR0000487605
First Posted: July 14, 2006    Key Record Dates
Last Update Posted: May 2, 2012
Last Verified: May 2012

Keywords provided by National Institutes of Health Clinical Center (CC):
adult anaplastic oligodendroglioma
adult gliosarcoma
adult mixed glioma
adult anaplastic astrocytoma
recurrent adult brain tumor
adult glioblastoma
adult giant cell glioblastoma

Additional relevant MeSH terms:
Glioma
Nervous System Neoplasms
Central Nervous System Neoplasms
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
Carboplatin
Antineoplastic Agents