Chemotherapy Plus Peripheral Stem Cell Transplant in Treating Patients With Central Nervous System Cancer

CAMP 004A - Phase 2 Study Of Intensive Chemotherapy (BET) For Selected Categories Of Malignant Central Nervous System Tumor

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplant may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells.

PURPOSE: This phase II trial is studying how well chemotherapy and peripheral stem cell transplant work in treating patients with central nervous system cancer.

Study Overview

• Status: Completed
• Conditions: Lymphoma; Head and Neck Cancer; Brain and Central Nervous System Tumors
• Intervention / Treatment: Drug: cyclophosphamide; Drug: etoposide; Drug: thiotepa; Procedure: adjuvant therapy; Drug: cisplatin; Procedure: peripheral blood stem cell transplantation; Biological: filgrastim; Procedure: autologous bone marrow transplantation; Drug: carmustine; Procedure: bone marrow ablation with stem cell support

Detailed Description

OBJECTIVES:

• Determine the response rate in patients with central nervous system malignancies treated with intensive chemotherapy supported by autologous peripheral blood stem cell transplantation following surgical resection and/or radiotherapy.
• Determine the disease-free survival and overall survival of this patient population treated with these regimens.
• Determine the toxicity of this high-dose chemotherapy regimen in these patients.
• Assess the quality of life of these patients following these treatment regimens.

OUTLINE: Patients with anaplastic astrocytoma, esthesioneuroblastoma, germ cell tumor, or primary neuroectodermal tumor undergo initial surgical resection followed by conventional or stereotactic radiotherapy. Patients with germ cell or primary neuroectodermal tumors also receive 4 courses of standard chemotherapy comprising cyclophosphamide, etoposide, and cisplatin prior to high-dose chemotherapy.

All patients undergo peripheral blood stem cell or bone marrow harvest followed by high-dose chemotherapy consolidation. Patients receive thiotepa IV 3 times daily on days -7 to -3, carmustine IV over 1 hour on days -6 to -3, and etoposide IV over 5 hours on days -6 to -3. Patients then undergo transplantation on day 0. Filgrastim (G-CSF) is administered concurrently with stem cell harvesting and transplantation.

Patients with recurrent oligodendroglioma or CNS lymphoma who have not received radiotherapy at diagnosis undergo conventional radiotherapy 6 weeks after completion of high-dose chemotherapy.

Patients are followed every 2-3 months for 1 year and then annually for 5 years. Quality of life is assessed at follow-up.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study over 3 years.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center

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 malignant tumors

  • Anaplastic astrocytoma
  • Oligodendroglioma
  • Germ cell tumor
  • Medulloblastoma
  • Primary neuroectodermal tumor
  • Esthesioneuroblastoma
  • CNS lymphoma (primary or systemic disease)
• Multifocal intracranial disease allowed
• No extraneural metastases (except controlled systemic lymphoma)

• Pretreatment considerations based on tumor type

  • Anaplastic astrocytoma:

    • Recurrent disease
    • Any treatment at diagnosis allowed (carmustine dose limited to 480 mg/m2)
    • Chemotherapy not required at recurrence

  • Oligodendroglioma:

    • Disease response (at least minor) to conventional chemotherapy OR
    • Recurrent disease

  • Esthesioneuroblastoma:

    • Attempted complete surgical resection
    • Disease progression after radiotherapy
    • Response to chemotherapy regimen comprising cyclophosphamide, etoposide, and cisplatin

  • CNS lymphoma:

    • Disease refractory to methotrexate OR
    • Failure after initial treatment with methotrexate OR
    • Considered at high risk for disease relapse despite initial response
• Radiographic or pathological confirmation of recurrent disease required
• Not eligible for other high priority national or institutional clinical studies

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG or Zubrod 0-1

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Not specified

Renal:

• Creatinine less than 1.5 times normal

Cardiovascular:

• LVEF at least 45%

Pulmonary:

• DLCO at least 60% predicted OR
• Approval of pulmonologist

Other:

• Not pregnant or nursing
• HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• See Disease Characteristics
• No other concurrent chemotherapy

Endocrine therapy:

• No concurrent anticancer hormonal therapy
• No concurrent steroids as antiemetics

Radiotherapy:

• See Disease Characteristics

Surgery:

• See Disease Characteristics

Other:

• No concurrent barbiturates or acetaminophen
• Participation in other concurrent supportive care or gene therapy trials allowed

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Toxicity
Response rate
Overall survival
Quality of life
Disease-free suvival

Collaborators and Investigators

• Sponsor: Herbert Irving Comprehensive Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Charles S. Hesdorffer, MD, Herbert Irving Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start: April 1, 1999
• Primary Completion (Actual): February 1, 2005
• Study Completion (Actual): May 1, 2008

Study Registration Dates

• First Submitted: January 6, 2001
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): February 4, 2013
• Last Update Submitted That Met QC Criteria: February 1, 2013
• Last Verified: July 1, 2007

More Information

Terms related to this study

• Keywords: recurrent esthesioneuroblastoma of the paranasal sinus and nasal cavity; recurrent adult brain tumor; adult anaplastic astrocytoma; adult anaplastic oligodendroglioma; adult central nervous system germ cell tumor; adult medulloblastoma; adult oligodendroglioma; primary central nervous system non-Hodgkin lymphoma
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms; Neoplasms by Site; Nervous System Neoplasms; Central Nervous System Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Cyclophosphamide; Etoposide; Thiotepa; Carmustine
• Other Study ID Numbers: CDR0000068360; CPMC-IRB-8445; CPMC-CAMP-004A; NCI-G00-1881