Temozolomide and Vinorelbine in Treating Patients With Recurrent Brain Metastases

Metastatic Cancer Clinical Trial

Official title:

A Phase I/II Trial Of Temozolomide And Vinorelbine For Patients With Recurrent Brain Metastases

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00026494
• Other study ID #: 01-088
• Secondary ID: MSKCC-01088ANCI-
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: November 9, 2001
• Last updated: December 15, 2015
• Start date: July 2001
• Est. completion date: April 2008

Study information

• Verified date: December 2015
• Source: Memorial Sloan Kettering Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: April 2008
• Est. primary completion date: April 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Metastatic Cancer
• Neoplasm Metastasis

Intervention

Drug:
• temozolomide

• vinorelbine tartrate

Locations

Country	Name	City	State
United States	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois
United States	Memorial Sloan-Kettering Cancer Center	New York	New York

Sponsors (3)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center	National Cancer Institute (NCI), Northwestern Memorial Hospital

Country where clinical trial is conducted

United States, 

References & Publications (1)

Iwamoto FM, Omuro AM, Raizer JJ, Nolan CP, Hormigo A, Lassman AB, Gavrilovic IT, Abrey LE. A phase II trial of vinorelbine and intensive temozolomide for patients with recurrent or progressive brain metastases. J Neurooncol. 2008 Mar;87(1):85-90. Epub 200 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Radiographic Response Assessed by Macdonald Criteria Every 2 Months	All patients will have their tumor measurements recorded at baseline and at the time of each MRI scan. Lesions must be measured in two dimensions.	2 years	No