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A Phase I/II Study of ATN-161 and Carboplatin in Adult Patients With Recurrent Intracranial Malignant Glioma


Phase 1/Phase 2
18 Years
N/A
Not Enrolling
Both
Brain and Central Nervous System Tumors

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Trial Information

A Phase I/II Study of ATN-161 and Carboplatin in Adult Patients With Recurrent Intracranial Malignant Glioma


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.

Inclusion 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

Type of Study:

Interventional

Study Design:

Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Safety

Safety Issue:

Yes

Principal Investigator

Howard A. Fine, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

NCI - Neuro-Oncology Branch

Authority:

United States: Food and Drug Administration

Study ID:

060170

NCT ID:

NCT00352313

Start Date:

May 2006

Completion Date:

January 2008

Related Keywords:

  • Brain and Central Nervous System Tumors
  • adult anaplastic oligodendroglioma
  • adult gliosarcoma
  • adult mixed glioma
  • adult anaplastic astrocytoma
  • recurrent adult brain tumor
  • adult glioblastoma
  • adult giant cell glioblastoma
  • Glioma
  • Nervous System Neoplasms
  • Central Nervous System Neoplasms

Name

Location

Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral OfficeBethesda, Maryland  20892-1182