Clinical trial NCT00026494: Temozolomide and Vinorelbine in Treating Patients With Recurrent Brain Metastases
Official title: A Phase I/II Trial Of Temozolomide And Vinorelbine For Patients With Recurrent Brain Metastases
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Metastatic Cancer
Keywords: tumors metastatic to brain
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: Northwestern Memorial Hospital
First posted: 2003-01-27
Enrollment: 49
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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 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.

Primary outcomes:
measure: Radiographic Response Assessed by Macdonald Criteria Every 2 Months
timeFrame: 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Robert H. Lurie Comprehensive Cancer Center at Northwestern University
state: Illinois
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Lauren E. Abrey, MD
role: STUDY_CHAIR
References:
citation: 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. doi: 10.1007/s11060-007-9491-3. Epub 2007 Nov 7.