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Rebeccamycin Analogue in Treating Women With Stage IIIB or Stage IV Breast Cancer

Primary Purpose

Male Breast Cancer, Recurrent Breast Cancer, Stage IIIB Breast Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
becatecarin
laboratory biomarker analysis
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Male Breast Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Patients must have histologically or cytologically confirmed invasive breast cancer; patients without pathologic or cytologic evidence of metastatic disease should have unequivocal evidence of metastasis on radiographic study or physical exam; patients must have metastatic (stage IV) breast cancer, or locally advanced (stage IIIB) breast cancer that cannot be treated with curative intent Patients must have measurable disease, defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 10 mm with conventional techniques; lytic bone lesions meeting these criteria will be considered measurable disease Patients are required to have had at least one prior chemotherapy regimen for advanced breast cancer unless they have progressed within 12 months of concluding adjuvant chemotherapy; patients may not have had more than 2 prior chemotherapy regimens for advanced breast cancer; treatment with high-dose chemotherapy and stem cell support in the metastatic setting, including induction chemotherapy, will be considered 2 treatment regimens; patients may have received adjuvant chemotherapy; patients who have metastatic breast cancer diagnosed within 12 months of concluding adjuvant chemotherapy will be eligible after 0 or 1 regimens in the metastatic setting; patients may have received prior hormonal therapy of any type; patients may have been previously treated with investigational agents or biological agents (e.g. Herceptin) Patients must have concluded prior therapy no less than the duration of one cycle of treatment prior to beginning treatment with rebeccamycin analog, but in all cases there must be at least a 2 week interval since last treatment; thus, if a patient is receiving therapy every three weeks, the patient must be at least three weeks from the last treatment before beginning protocol-based therapy; patients must have recovered from the toxicities of prior therapy, and meet the performance status and laboratory criteria for eligibility before beginning treatment Patients may not receive concurrent anti-neoplastic therapy; all other radiation therapy, hormonal therapy, or treatment with trastuzumab (Herceptin) must be stopped prior to treatment on protocol; patients receiving bisphosphonate therapy may continue to receive these treatments while on protocol Life expectancy of greater than 3 months ECOG performance status =< 1 (Karnofsky >= 70%) Absolute neutrophil count (ANC) >= 1,500/uL Platelets >= 100,000/uL Total bilirubin within normal institutional limits AST(SGOT)/ALT(SGPT) =< 2.5 x institutional upper limit of normal Creatinine =< 2 mg/dl Sodium (Na) within normal institutional limits Serum lipase within normal institutional limits Serum amylase within normal institutional limits Because rebeccamycin analog has been associated with phlebitis, all therapy on protocol will be given through a central venous line; patients not willing to have a central line, or those in whom central venous access could not be established, will not be eligible The effects of rebeccamycin analog on the developing human fetus at the recommended therapeutic dose are unknown; for this reason, women of child-bearing potential must agree to use adequate contraception prior to study entry and for the duration of study participation; women should not become pregnant or nurse, nor expect to become pregnant or nurse, during the study; women in whom there is a suspicion of possible pregnancy must have a documented negative serum pregnancy test prior to beginning therapy; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: Patients with only non-measurable disease, defined as all other lesions, including small lesions (longest diameter < 10 mm with conventional techniques) and truly non-measurable lesions, which include the following: Bone lesions, except pure lytic lesions Leptomeningeal disease Tumor markers Ascites Pleural/pericardial effusions Patients who have had radiotherapy within 2 weeks prior to entering the study or those who have not recovered from adverse events due to prior chemotherapy administered previously Patients may not be receiving any other investigational anti-neoplastic agents, with the following exceptions: patients may participate in concurrent studies of supportive therapies, including anti-nausea or bisphosphonate-based treatments Patients with known brain metastases may be included if they meet the following 2 criteria: Completed whole brain irradiation at least two months prior to study entry Have no symptoms from brain metastases Lack of central venous access Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated on study HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study

Sites / Locations

  • Dana-Farber Cancer Institute

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Arm I (becatecarin)

Arm II (becatecarin)

Arm Description

Patients receive rebeccamycin analogue IV over 60 minutes on day 1.

Patients receive rebeccamycin analogue IV over 60 minutes on days 1-5.

Outcomes

Primary Outcome Measures

Response rates (complete or partial response) of 2 different schedules of rebeccamycin analog
Toxicity rates of rebeccamycin analog as assessed by the NCI CTC version 2.0

Secondary Outcome Measures

Change in topoisomerase (TOPO I and II) levels in circulating lymphocytes
Changes in TOPO levels will be described as a function of treatment and time since exposure in order to establish whether rebeccamycin acts as an inhibitor of these enzymes.

Full Information

First Posted
June 2, 2000
Last Updated
January 31, 2013
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00005817
Brief Title
Rebeccamycin Analogue in Treating Women With Stage IIIB or Stage IV Breast Cancer
Official Title
A Randomized Phase 2 Study of Rebeccamycin Analog in Advanced Breast Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
January 2013
Overall Recruitment Status
Completed
Study Start Date
March 2000 (undefined)
Primary Completion Date
May 2006 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
Randomized phase II trial to compare the effectiveness of two regimens of rebeccamycin analogue in treating women who have stage IIIB or stage IV breast cancer. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. The best way to give rebeccamycin analog in breast cancer patients is not yet known
Detailed Description
PRIMARY OBJECTIVES: I. To assess the activity of rebeccamycin analog as therapy for advanced breast cancer when administered in two different treatment schedules. SECONDARY OBJECTIVES: I. To assess the toxicity associated with administration of rebeccamycin analog therapy in women with advanced breast cancer. II. To evaluate topoisomerase I and II levels in human lymphocytes following treatment with rebeccamycin analog. OUTLINE: This is a randomized, multicenter study. Patients are randomized to one of two treatment arms. Arm I: Patients receive rebeccamycin analogue IV over 60 minutes on day 1. Arm II: Patients receive rebeccamycin analogue IV over 60 minutes on days 1-5. In all arms, courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Male Breast Cancer, Recurrent Breast Cancer, Stage IIIB Breast Cancer, Stage IV Breast Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
42 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm I (becatecarin)
Arm Type
Experimental
Arm Description
Patients receive rebeccamycin analogue IV over 60 minutes on day 1.
Arm Title
Arm II (becatecarin)
Arm Type
Experimental
Arm Description
Patients receive rebeccamycin analogue IV over 60 minutes on days 1-5.
Intervention Type
Drug
Intervention Name(s)
becatecarin
Other Intervention Name(s)
BMS-181176, rebeccamycin analogue, rebeccamycin analogue, tartrate salt, XL119
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Response rates (complete or partial response) of 2 different schedules of rebeccamycin analog
Time Frame
Up to 6 years
Title
Toxicity rates of rebeccamycin analog as assessed by the NCI CTC version 2.0
Time Frame
Up to 6 years
Secondary Outcome Measure Information:
Title
Change in topoisomerase (TOPO I and II) levels in circulating lymphocytes
Description
Changes in TOPO levels will be described as a function of treatment and time since exposure in order to establish whether rebeccamycin acts as an inhibitor of these enzymes.
Time Frame
From baseline to up to 6 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients must have histologically or cytologically confirmed invasive breast cancer; patients without pathologic or cytologic evidence of metastatic disease should have unequivocal evidence of metastasis on radiographic study or physical exam; patients must have metastatic (stage IV) breast cancer, or locally advanced (stage IIIB) breast cancer that cannot be treated with curative intent Patients must have measurable disease, defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 10 mm with conventional techniques; lytic bone lesions meeting these criteria will be considered measurable disease Patients are required to have had at least one prior chemotherapy regimen for advanced breast cancer unless they have progressed within 12 months of concluding adjuvant chemotherapy; patients may not have had more than 2 prior chemotherapy regimens for advanced breast cancer; treatment with high-dose chemotherapy and stem cell support in the metastatic setting, including induction chemotherapy, will be considered 2 treatment regimens; patients may have received adjuvant chemotherapy; patients who have metastatic breast cancer diagnosed within 12 months of concluding adjuvant chemotherapy will be eligible after 0 or 1 regimens in the metastatic setting; patients may have received prior hormonal therapy of any type; patients may have been previously treated with investigational agents or biological agents (e.g. Herceptin) Patients must have concluded prior therapy no less than the duration of one cycle of treatment prior to beginning treatment with rebeccamycin analog, but in all cases there must be at least a 2 week interval since last treatment; thus, if a patient is receiving therapy every three weeks, the patient must be at least three weeks from the last treatment before beginning protocol-based therapy; patients must have recovered from the toxicities of prior therapy, and meet the performance status and laboratory criteria for eligibility before beginning treatment Patients may not receive concurrent anti-neoplastic therapy; all other radiation therapy, hormonal therapy, or treatment with trastuzumab (Herceptin) must be stopped prior to treatment on protocol; patients receiving bisphosphonate therapy may continue to receive these treatments while on protocol Life expectancy of greater than 3 months ECOG performance status =< 1 (Karnofsky >= 70%) Absolute neutrophil count (ANC) >= 1,500/uL Platelets >= 100,000/uL Total bilirubin within normal institutional limits AST(SGOT)/ALT(SGPT) =< 2.5 x institutional upper limit of normal Creatinine =< 2 mg/dl Sodium (Na) within normal institutional limits Serum lipase within normal institutional limits Serum amylase within normal institutional limits Because rebeccamycin analog has been associated with phlebitis, all therapy on protocol will be given through a central venous line; patients not willing to have a central line, or those in whom central venous access could not be established, will not be eligible The effects of rebeccamycin analog on the developing human fetus at the recommended therapeutic dose are unknown; for this reason, women of child-bearing potential must agree to use adequate contraception prior to study entry and for the duration of study participation; women should not become pregnant or nurse, nor expect to become pregnant or nurse, during the study; women in whom there is a suspicion of possible pregnancy must have a documented negative serum pregnancy test prior to beginning therapy; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: Patients with only non-measurable disease, defined as all other lesions, including small lesions (longest diameter < 10 mm with conventional techniques) and truly non-measurable lesions, which include the following: Bone lesions, except pure lytic lesions Leptomeningeal disease Tumor markers Ascites Pleural/pericardial effusions Patients who have had radiotherapy within 2 weeks prior to entering the study or those who have not recovered from adverse events due to prior chemotherapy administered previously Patients may not be receiving any other investigational anti-neoplastic agents, with the following exceptions: patients may participate in concurrent studies of supportive therapies, including anti-nausea or bisphosphonate-based treatments Patients with known brain metastases may be included if they meet the following 2 criteria: Completed whole brain irradiation at least two months prior to study entry Have no symptoms from brain metastases Lack of central venous access Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated on study HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Harold Burstein
Organizational Affiliation
Dana-Farber Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States

12. IPD Sharing Statement

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Rebeccamycin Analogue in Treating Women With Stage IIIB or Stage IV Breast Cancer

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