A Phase II Study of Irinotecan and Temozolomide in Breast Cancer Patients With Brian Metastases That Have Progressed After Stereotactic Radiosurgery or Whole Brain Radiation
Overview
- Phase
- Phase 2
- Intervention
- temozolomide
- Conditions
- Breast Cancer
- Sponsor
- University of California, San Francisco
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- Number of Patients With Objective Treatment Response (Complete or Partial) in the CNS
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
RATIONALE: Drugs used in chemotherapy, such as irinotecan and temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells.
PURPOSE: This phase II trial is studying the side effects of giving irinotecan together with temozolomide and to see how well it works in treating patients with breast cancer who have received previous treatment for brain metastases.
Detailed Description
OBJECTIVES: Primary * To evaluate the objective response rate systemically and in the CNS to the combination of irinotecan hydrochloride and temozolomide among patients with breast cancer and progressive brain metastases that have progressed after previous treatment for brain metastases. * To determine the toxicities associated with the combination of irinotecan hydrochloride and temozolomide in breast cancer patients with progressive brain metastases. Secondary * To evaluate the time to first progression at any site (CNS or extra-CNS) in patients treated with the combination of irinotecan hydrochloride and temozolomide. * To evaluate the overall survival of patients treated with the combination of irinotecan hydrochloride and temozolomide for brain metastases. OUTLINE: Patients receive irinotecan IV on days 1 and 15 and oral temozolomide on days 1-7 and 15-21. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients are followed every 4 weeks.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
irinotecan and temozolomide
Intervention: temozolomide
irinotecan and temozolomide
Intervention: irinotecan hydrochloride
Outcomes
Primary Outcomes
Number of Patients With Objective Treatment Response (Complete or Partial) in the CNS
Time Frame: Baseline scan prior to study entry was performed within 14 days of cycle 1 day 1, then every 8 weeks from then until disease progression or up to 2 years
Imaging was performed at 8-week intervals to assess response to treatment. Patients with known or suspected leptomeningeal disease were deemed to have a complete response if CSF cytology converted to negative (if positive at baseline) and all meningeal enhancement or nodularity of brain and/or spine MRI resolved. A modified RECIST 1.0 criteria was used to assess CNS response for patients with new or progressing brain metastases. In this modified RECIST criteria, CNS lesions \<1cm were not considered measurable, but were considered evaluable for response and progression. Progressive disease for patients with lesions \<1 cm was defined as follows: growth of a lesion from less than or equal to 5 mm to greater than or equal to 10mm; or, growth of a 6-9 mm lesion by at least 5 mm in the case of non-target parenchymal brain metastases.
Number of Patients Experiencing a Clinical Benefit
Time Frame: From 1 day 1 (first day of treatment) every 8 weeks until scan shows disease progression or up to 2 years
The number of patients experiencing a clinical benefit is the sum of patients with an objective response plus patients with stable disease at ≥ 16 weeks from cycle 1 day 1 (first day of treatment). If a patient did not come back for a follow up scan after clinical deterioration, then they were only considered stable up to the time of the last scan they had per protocol.
Secondary Outcomes
- Time to First Progression in CNS(Baseline scan prior to study entry was performed within 14 days of cycle 1 day 1, then every 8 weeks from then until disease progression or up to 2 years)
- Overall Time of Survival(Time from initiation of study participation until death or up to 3 years)
- Number of Patients Whose Circulating Tumor Cells (CTCs) Decreased From >5 to <5 CTCs Per 7.5 mL(CTCs drawn on cycle 1 day 1, collection at 8 week intervals on patients who did not progress on their 8 week scans up to 2 years)