Irinotecan and Temozolomide in Treating Patients With Breast Cancer Who Have Received Previous Treatment for Brain Metastases

University of California San Francisco (UCSF)

Status and phase

Completed

Phase 2

Conditions

Metastatic Cancer

Breast Cancer

Treatments

Drug: temozolomide

Drug: irinotecan hydrochloride

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00617539

UCSF-05751

05751

Details and patient eligibility

About

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.

Full 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.

Enrollment

30 patients

Sex

All

Ages

18 to 120 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

Histologically or cytologically confirmed breast cancer with radiographically confirmed metastases to the brain
- Extracranial metastases allowed
Must have demonstrated progression of brain metastases after prior treatment for brain metastases, including any of the following:
- External beam radiotherapy
- Brachytherapy
- Stereotactic radiosurgery
- Surgery
- Chemotherapy
- Treatments with investigational drugs, biologics, or devices
Disease progression in the CNS must meet ≥ 1 of the following criteria:
- New lesions in the CNS on an imaging study (contrast-enhanced CT scan or MRI)
- Progressive lesions on an imaging study (contrast-enhanced CT scan or MRI)
New or progressive lesions that do not meet measurable disease definition allowed
Leptomeningeal disease allowed if concurrent progression or parenchymal brain metastases
Not a candidate for surgical resection and/or further stereotactic radiosurgery
Hormone receptor status not specified

PATIENT CHARACTERISTICS:

Menopausal status not specified
ECOG performance status 0-2
Life expectancy ≥ 1 month
Hemoglobin ≥ 10 g/dL (transfusion allowed)
ANC ≥ 1,500/mm³
Granulocyte count ≥ 1,500/mm³
Platelet count ≥ 100,000/mm³
Creatinine ≤ 1.5 mg/dL
Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
AST and ALT ≤ 3 times ULN
Must be able to swallow and retain oral medications
No other active malignancy except for any of the following:
- Curatively treated basal or squamous cell carcinoma of the skin
- Carcinoma in situ of the cervix
- Other malignancies considered disease-free
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No history of immediate or delayed-type hypersensitivity reaction to gadolinium contrast agents or other contraindication to gadolinium contrast
No other known contraindication to MRI including, but not limited to, any of the following:
- Cardiac pacemaker
- Implanted cardiac defibrillator
- Brain aneurysm clips
- Cochlear implant
- Ocular foreign body
- Shrapnel
No active or uncontrolled infection

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
Recovered from the side effects of prior chemotherapy, surgery, or radiotherapy for extracranial disease or brain metastases
Concurrent trastuzumab, bisphosphonate, and/or corticosteroid therapy allowed
At least 1 week since prior or on current stable dose of corticosteroid therapy
Patients on an enzyme-inducing anti-epileptic agent (EIAE) or valproic acid are eligible if they are switched to an alternate non-EIAE medication
Concurrent coumadin allowed
No prophylactic use of filgrastim (G-CSF) during first course of treatment