Temozolomide and Vinorelbine in Treating Patients With Recurrent Brain Metastases

This study has been completed.
Sponsor:
Collaborators:
Northwestern Memorial Hospital
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT00026494
First received: November 9, 2001
Last updated: March 1, 2013
Last verified: March 2013
  Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase I/II trial to study the effectiveness of temozolomide and vinorelbine in treating patients who have recurrent brain metastases.


Condition Intervention Phase
Metastatic Cancer
Drug: temozolomide
Drug: vinorelbine tartrate
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Trial Of Temozolomide And Vinorelbine For Patients With Recurrent Brain Metastases

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • Maximum tolerated dose (phase I) assessed by NCI CTC at 2 months [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Radiographic response (phase II) assessed by Macdonald criteria every 2 months [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Progression-free survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Enrollment: 49
Study Start Date: July 2001
Study Completion Date: April 2008
Primary Completion Date: April 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Temozolomide and Vinorelbine
Patients will be treated with vinorelbine on days 1 and 8 of each cycle; temozolomide will be administered on days 1 to 7 and 15 to 21 of each cycle. The dose level of temozolomide will be given at a dose of 150 mg/m2/day. A cycle will be defined as 28 days of treatment.
Drug: temozolomide Drug: vinorelbine tartrate

Detailed Description:

OBJECTIVES:

  • Determine the maximum tolerated dose of vinorelbine when administered in combination with temozolomide in patients with recurrent brain metastases (phase I accrual completed).
  • Determine the safety and feasibility of this treatment regimen in these patients.
  • Determine the efficacy of this treatment regimen, in terms of objective radiographic response and overall and progression-free survival, in these patients.

OUTLINE: This is a dose-escalation study of vinorelbine.

Patients receive vinorelbine IV over 5-10 minutes on days 1 and 8 and oral temozolomide once daily on days 1-7 and 15-21. Courses repeat every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of vinorelbine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 6 patients experience dose-limiting toxicity. Once the MTD is determined, an additional 20-35 patients will be treated at that dose level.

Patients are followed every 3-4 months.

PROJECTED ACCRUAL: A minimum of 3 patients will be accrued for the phase I portion of this study and 20-35 patients will be accrued for the phase II portion of this study within 2 years.

  Eligibility

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

INCLUSION CRITERIAL:

  • Age > or = 18 years.
  • Karnofsky performance score > or = 60.
  • Histopathologic confirmation of the diagnosis of a solid tumor malignancy. The brain metastasis diagnosis per se does not have to be pathologically confirmed if the clinical and neuro radiographic picture is typical.
  • MRI (or CT if the patient cannot undergo MRI) evidence of evaluable disease in the brain.
  • Absolute neutrophil count > or = 1,500/mm³. Platelet count > or = 100,000/mm³.
  • Hemoglobin > or = 10 g/dl.
  • BUN and serum creatinine both < 1.5 times upper limit of normal.
  • Total and direct bilirubin both < 1.5 times upper limit of normal.
  • SGOT and SGPT both < or = 3 times upper limit of normal.
  • Alkaline phosphatase < or = 2 times upper limit of normal.
  • At least two weeks must have elapsed from brain biopsy, craniotomy, or other surgery.
  • Life expectancy > or = 8 weeks.
  • Patient or their legal guardian or legal next-of-kin must provide written informed consent prior to patient's registration on study.
  • At least four weeks must have elapsed from previous external beam radiation therapy, or eight weeks from stereotactic radiosurgery.
  • Patients treated with radiosurgery should have evidence of progression at a distant site in the brain, or confirmation of tumor progression by biopsy or PET scan.

EXCLUSION CRITERIA:

  • Previous treatment with temozolomide, dacarbazine or vinorelbine.
  • Patients who have not recovered from all acute toxicities of prior therapies.
  • Patients with evidence of leptomeningeal metastases or primary dural metastases.
  • Patients who are poor medical risks because of nonmalignant systemic disease, as well as those with acute infection requiring treatment with intravenous antibiotics.
  • Patients whose psychiatric condition would, in the judgment of the principal investigator, make it unlikely that they could adhere to the requirements of the protocol.
  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: NCT00026494

Locations
United States, Illinois
Robert H. Lurie Comprehensive Cancer Center at Northwestern University
Chicago, Illinois, United States, 60611-3013
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Northwestern Memorial Hospital
Investigators
Study Chair: Lauren E. Abrey, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
Publications:
Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT00026494     History of Changes
Other Study ID Numbers: 01-088, MSKCC-01088A, NCI-G01-2025
Study First Received: November 9, 2001
Last Updated: March 1, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Memorial Sloan-Kettering Cancer Center:
tumors metastatic to brain

Additional relevant MeSH terms:
Neoplasm Metastasis
Neoplasms
Neoplasms, Second Primary
Neoplastic Processes
Pathologic Processes
Temozolomide
Dacarbazine
Vinorelbine
Vinblastine
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators

ClinicalTrials.gov processed this record on July 26, 2014