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

NCT00617539 | Completed Phase 2 Results DMC

• 2 other identifiers: 05751UCSF-05751
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Breast Cancer; Metastatic Cancer

Keywords

recurrent breast cancer; stage IV breast cancer; male breast cancer; tumors metastatic to brain

Outcome Measures

Primary Outcomes (2)

• Number of Patients With Objective Treatment Response (Complete or Partial) in the CNS

  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.

  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

• Number of Patients Experiencing a Clinical Benefit

  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.

  From 1 day 1 (first day of treatment) every 8 weeks until scan shows disease progression or up to 2 years

Secondary Outcomes (3)

• 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

Study Arms (1)

irinotecan and temozolomide

EXPERIMENTAL

Drug: irinotecan hydrochloride; Drug: temozolomide

Interventions

irinotecan hydrochloride DRUG

irinotecan and temozolomide

temozolomide DRUG

irinotecan and temozolomide

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• University of California, San Francisco: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94115, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Neoplasm Metastasis; Breast Neoplasms, Male; Brain Neoplasms

Interventions

Irinotecan; Temozolomide

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Michelle Melisko, MD
• Organization: University of California San Francisco

Michelle.Melisko@ucsf.edu

415-353-7070

Study Officials

• Michelle Melisko, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 15, 2008
• First Posted: February 18, 2008
• Study Start: February 1, 2005
• Primary Completion: January 1, 2013
• Study Completion: January 1, 2014
• Last Updated: April 20, 2018
• Results First Posted: April 20, 2018

Record last verified: 2018-03

Locations

US (1)