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

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ClinicalTrials.gov Identifier: NCT00617539
Recruitment Status : Completed
First Posted : February 18, 2008
Results First Posted : April 20, 2018
Last Update Posted : April 20, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University of California, San Francisco

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.


Condition or disease Intervention/treatment Phase
Breast Cancer Metastatic Cancer Drug: irinotecan hydrochloride Drug: temozolomide Phase 2

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.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : February 2005
Actual Primary Completion Date : January 2013
Actual Study Completion Date : January 2014


Arm Intervention/treatment
Experimental: irinotecan and temozolomide Drug: irinotecan hydrochloride Drug: temozolomide



Primary Outcome Measures :
  1. 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.

  2. 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 Outcome Measures :
  1. Time to First Progression in 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 at 8-week intervals to assess response to treatment. A modified RECIST 1.0 criteria was used to assess response and time to progression in the CNS for patients with 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.

    If patient did not come back for a follow up scan after clinical deterioration, patient was only considered stable up to the time of the last scan per protocol and time to progression would be from cycle 1 day 1 to the last scan they completed that was stable.


  2. Overall Time of Survival [ Time Frame: Time from initiation of study participation until death or up to 3 years ]
    Time from initiation of study participation until death

  3. Number of Patients Whose Circulating Tumor Cells (CTCs) Decreased From >5 to <5 CTCs Per 7.5 mL [ Time Frame: 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 ]
    CTCs were measured in blood using the Cellsearch(R) assay in 14 of the 20 patients measured at baseline



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Ages Eligible for Study:   18 Years to 120 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00617539


Locations
United States, California
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States, 94115
Sponsors and Collaborators
University of California, San Francisco
National Cancer Institute (NCI)
Investigators
Principal Investigator: Michelle Melisko, MD University of California, San Francisco

Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT00617539     History of Changes
Other Study ID Numbers: 05751
UCSF-05751
First Posted: February 18, 2008    Key Record Dates
Results First Posted: April 20, 2018
Last Update Posted: April 20, 2018
Last Verified: March 2018

Keywords provided by University of California, San Francisco:
recurrent breast cancer
stage IV breast cancer
male breast cancer
tumors metastatic to brain

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasm Metastasis
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Neoplastic Processes
Pathologic Processes
Irinotecan
Camptothecin
Temozolomide
Dacarbazine
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Alkylating
Alkylating Agents