Radiation Therapy, Temozolomide, Tamoxifen, and Carboplatin in Treating Patients With Malignant Gliomas

A Phase II Pilot Trial of Radiation Therapy With Concurrent and Adjuvant Temozolomide, Tamoxifen and Carboplatin (T2C) in the Treatment of Patients With Primary Central Nervous System Malignant Gliomas

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as temozolomide and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Tamoxifen may make tumor cells more sensitive to radiation therapy and chemotherapy. Giving radiation therapy together with temozolomide, tamoxifen, and carboplatin may kill more tumor cells.

PURPOSE: This phase II trial is studying the side effects and how well giving radiation therapy together with temozolomide, tamoxifen, and carboplatin works in treating patients with malignant gliomas.

Study Overview

• Status: Unknown
• Conditions: Brain and Central Nervous System Tumors
• Intervention / Treatment: Drug: carboplatin; Radiation: radiation therapy; Drug: temozolomide; Procedure: adjuvant therapy; Drug: tamoxifen citrate

Detailed Description

OBJECTIVES:

• Determine the progression-free and overall survival of patients with supratentorial malignant gliomas (WHO grade III or IV) receiving radiotherapy with concurrent and adjuvant temozolomide, tamoxifen citrate, and carboplatin.
• Determine the acute and delayed treatment-related toxicities in these patients.
• Determine tumor response in patients with postoperative measurable disease.

OUTLINE: This is an open-label, pilot study.

• Induction therapy: Patients receive oral temozolomide twice daily and oral tamoxifen citrate twice daily on days 1-42 and carboplatin IV over 60 minutes on days 1, 8, 15, 22, 29, and 36. Patients also receive radiotherapy on days 1-5 in weeks 1-6.
• Consolidation therapy: Beginning 4 weeks after the completion of induction therapy, patients receive temozolomide, tamoxifen citrate, and carboplatin as in induction therapy. Treatment repeats every 8 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for 5 years.

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Encinitas, California, United States, 92024
      • Recruiting
      • San Diego Pacific Oncology and Hematology Associates, Incorporated - Encinitas

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 glioblastoma multiforme and/or anaplastic astrocytoma

  • Supratentorial tumor
  • No well-differentiated astrocytoma or glioma with oligodendroglial component
  • No multifocal glioma
• Has undergone surgery within the past 6 weeks
• No recurrent glioblastoma multiforme

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Neurological functional status 0-2
• Life expectancy > 12 weeks
• ANC ≥ 1,200/mm³
• Platelet count ≥ 100,000/mm³
• Hemoglobin ≥ 9 g/dL
• Serum creatinine ≤ 1.5 times upper limit of normal (ULN)
• Blood urea nitrogen ≤ 1.5 times ULN
• Total and direct bilirubin ≤ 3 times ULN
• AST and ALT ≤ 3 times ULN
• Alkaline phosphatase ≤ 3 times ULN
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 3 months after study completion
• No other malignancies within the past 3 years, except for carcinoma in situ of the cervix or nonmelanoma skin cancer
• No acquired immune deficiency syndrome (AIDS)
• No major medical illness or psychiatric impairment that would preclude study compliance

PRIOR CONCURRENT THERAPY:

• No prior radiotherapy to the head and neck
• No other concurrent therapy for the tumor

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Masking: NONE

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Toxicity
Progression-free survival
Overall survival
Tumor response

Collaborators and Investigators

• Sponsor: San Diego Pacific Oncology & Hematology Associates

Study record dates

Study Major Dates

• Study Start: December 1, 2006
• Primary Completion (ANTICIPATED): July 1, 2009

Study Registration Dates

• First Submitted: June 25, 2007
• First Submitted That Met QC Criteria: June 25, 2007
• First Posted (ESTIMATE): June 27, 2007

Study Record Updates

• Last Update Posted (ESTIMATE): January 10, 2014
• Last Update Submitted That Met QC Criteria: January 9, 2014
• Last Verified: July 1, 2009

More Information

Terms related to this study

• Keywords: adult glioblastoma; adult giant cell glioblastoma; adult gliosarcoma; adult anaplastic astrocytoma
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioma; Nervous System Neoplasms; Central Nervous System Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Alkylating; Alkylating Agents; Hormone Antagonists; Bone Density Conservation Agents; Estrogen Antagonists; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Carboplatin; Temozolomide; Tamoxifen
• Other Study ID Numbers: CDR0000551555; POHA-0601