Clinical trial NCT00617539: Irinotecan and Temozolomide in Treating Patients With Breast Cancer Who Have Received Previous Treatment for Brain Metastases
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Metastatic Cancer
Keywords: recurrent breast cancer
stage IV breast cancer
male breast cancer
tumors metastatic to brain
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2008-02-18
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
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, 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.

Eligibility 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

Primary outcomes:
measure: Number of Patients With Objective Treatment Response (Complete or Partial) in the CNS
timeFrame: 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
measure: Number of Patients Experiencing a Clinical Benefit
timeFrame: From 1 day 1 (first day of treatment) every 8 weeks until scan shows disease progression or up to 2 years
Secondary outcomes:
measure: Time to First Progression in CNS
timeFrame: 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
measure: Overall Time of Survival
timeFrame: Time from initiation of study participation until death or up to 3 years
measure: Number of Patients Whose Circulating Tumor Cells (CTCs) Decreased From >5 to <5 CTCs Per 7.5 mL
timeFrame: 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
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: UCSF Helen Diller Family Comprehensive Cancer Center
state: California
Study officials:
affiliation: University of California, San Francisco
name: Michelle Melisko, MD
role: PRINCIPAL_INVESTIGATOR
References: