Phase II Trial of Bortezomib and Doxorubicin in Metastatic Breast Cancer
Study Details
Study Description
Brief Summary
Primary objective is to determine the effectiveness of the combination of bortezomib and doxorubicin in patients with metastatic breast cancer. The trial format is a single arm Phase II design wherein patients are treated with bortezomib IV on days 1, 4, 8, and 11 and with doxorubicin IV on days 1 and 8 of a 21-day cycle.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: A
|
Drug: PS-341, doxorubicin
bortezomib:1.3 mg/m2 IVP over 3-5 sec. days 1, 4, 8, 11 of 21 day cycle doxorubicin: 20 mg/m2 IV over 3-5 min. days 1,8 (one hour after bortezomib) of 21 day cycle
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Overall Response Rate [Every two cycles/42 days, up to 7 months]
Determine the clinical efficacy of bortezomib and doxorubicin in patients with metastatic breast cancer. Overall response rate is defined as both complete and partial response per RECIST, where complete response is the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10mm. Partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive disease is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm.
Secondary Outcome Measures
- Time to Progression [Up to one year]
Number of days to progression, where progression is defined as the number of days from the day of first study drug administration to the day the patient experiences an event of disease progression, or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. If a patient has not experienced an event of disease progression, then the patient's data will be censored at the date of the last available evaluation. Progression-free survival will be summarized by medium time to progression.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Cytologically or histologically confirmed metastatic breast cancer
-
Measurable or evaluable disease
-
Age > 18, PS 0,1,2
-
MUGA > 45%
-
Received one or fewer chemotherapies or investigational regimens for metastatic disease, no limit to the number of prior hormonal therapies. May have had single agent Herceptin and/or Herceptin plus single-agent chemotx.
-
Must meet designated laboratory criteria within 14 days of enrollment
Exclusion Criteria:
-
Doxorubicin for metatstatic disease.
-
Pregnant or lactating.
-
Active infections, no myocardial infarction within 2 months of enrollment.
-
Investigational drugs within 14 days of enrollment.
-
Chemotherapy, radiotherapy, hormonal therapy or other investigational therapy within 4 weeks of enrollment.
-
Neuropathy that is > grade 2.
-
Active brain mets.
-
Hypersensitivity to bortezomib, boron, or mannitol.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Wisconsin Paul P. Carbone Comprehensive Cancer Center | Madison | Wisconsin | United States | 53792 |
Sponsors and Collaborators
- University of Wisconsin, Madison
- National Cancer Institute (NCI)
- Millennium Pharmaceuticals, Inc.
Investigators
- Principal Investigator: James A Stewart, M.D., University of Wisconsin PPC Comprehensive Cancer Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2004-0130
- CO04101
- A534260
- SMPH/MEDICINE
Study Results
Participant Flow
| Recruitment Details | This study enrolled subjects with metastatic breast cancer from the Wisconsin Oncology Network (WON), which is driven by investigators at the University of Wisconsin Carbone Cancer Center, from August of 2006 through February of 2008. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Bortezomib and Doxorubicin |
|---|---|
| Arm/Group Description | Subjects received therapy on days 1, 4, 8, and 11 of a 21-day cycle. 1.3 mg/m2 of Bortezomib was administered intravenously over 3-5 seconds on days 1, 4, 8, and 11, no less than 72 hours apart. 20 mg/m2 of Doxorubicin was administered intravenously over 3-5 minutes on days 1 and 8, one hour after Bortezomib administrations. |
| Period Title: Overall Study | |
| STARTED | 4 |
| COMPLETED | 4 |
| NOT COMPLETED | 0 |
Baseline Characteristics
| Arm/Group Title | Bortezomib and Doxorubicin |
|---|---|
| Arm/Group Description | Subjects received therapy on days 1, 4, 8, and 11 of a 21-day cycle. 1.3 mg/m2 of Bortezomib was administered intravenously over 3-5 seconds on days 1, 4, 8, and 11, no less than 72 hours apart. 20 mg/m2 of Doxorubicin was administered intravenously over 3-5 minutes on days 1 and 8, one hour after Bortezomib administrations. |
| Overall Participants | 4 |
| Age (Count of Participants) | |
| <=18 years |
0
0%
|
| Between 18 and 65 years |
3
75%
|
| >=65 years |
1
25%
|
| Sex: Female, Male (Count of Participants) | |
| Female |
4
100%
|
| Male |
0
0%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |
| Hispanic or Latino |
0
0%
|
| Not Hispanic or Latino |
2
50%
|
| Unknown or Not Reported |
2
50%
|
| Race (NIH/OMB) (Count of Participants) | |
| American Indian or Alaska Native |
0
0%
|
| Asian |
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
| Black or African American |
0
0%
|
| White |
4
100%
|
| More than one race |
0
0%
|
| Unknown or Not Reported |
0
0%
|
| Region of Enrollment (Count of Participants) | |
| United States |
4
100%
|
Outcome Measures
| Title | Overall Response Rate |
|---|---|
| Description | Determine the clinical efficacy of bortezomib and doxorubicin in patients with metastatic breast cancer. Overall response rate is defined as both complete and partial response per RECIST, where complete response is the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10mm. Partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive disease is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm. |
| Time Frame | Every two cycles/42 days, up to 7 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Protocol accrued only 4 of 54 subjects, and was ultimately terminated. No data analysis was done. |
| Arm/Group Title | Bortezomib and Doxorubicin |
|---|---|
| Arm/Group Description | Subjects received therapy on days 1, 4, 8, and 11 of a 21-day cycle. 1.3 mg/m2 of Bortezomib was administered intravenously over 3-5 seconds on days 1, 4, 8, and 11, no less than 72 hours apart. 20 mg/m2 of Doxorubicin was administered intravenously over 3-5 minutes on days 1 and 8, one hour after Bortezomib administrations. |
| Measure Participants | 4 |
| Complete Response |
0
0%
|
| Partial Response |
1
25%
|
| Progressive Disease |
3
75%
|
| Title | Time to Progression |
|---|---|
| Description | Number of days to progression, where progression is defined as the number of days from the day of first study drug administration to the day the patient experiences an event of disease progression, or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. If a patient has not experienced an event of disease progression, then the patient's data will be censored at the date of the last available evaluation. Progression-free survival will be summarized by medium time to progression. |
| Time Frame | Up to one year |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Bortezomib and Doxorubicin |
|---|---|
| Arm/Group Description | Subjects received therapy on days 1, 4, 8, and 11 of a 21-day cycle. 1.3 mg/m2 of Bortezomib was administered intravenously over 3-5 seconds on days 1, 4, 8, and 11, no less than 72 hours apart. 20 mg/m2 of Doxorubicin was administered intravenously over 3-5 minutes on days 1 and 8, one hour after Bortezomib administrations. |
| Measure Participants | 4 |
| Median (Full Range) [days to progression] |
47
|
Adverse Events
| Time Frame | Adverse event data were collected for 1 year, 9 months. | |
|---|---|---|
| Adverse Event Reporting Description | Investigators conducted continuous reviews of data and participant safety at monthly meetings, where the results of each of each participant's treatment were discussed and the discussion was documented in the minutes. | |
| Arm/Group Title | Bortezomib and Doxorubicin | |
| Arm/Group Description | Subjects received therapy on days 1, 4, 8, and 11 of a 21-day cycle. 1.3 mg/m2 of Bortezomib was administered intravenously over 3-5 seconds on days 1, 4, 8, and 11, no less than 72 hours apart. 20 mg/m2 of Doxorubicin was administered intravenously over 3-5 minutes on days 1 and 8, one hour after Bortezomib administrations. | |
All Cause Mortality |
||
| Bortezomib and Doxorubicin | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/4 (0%) | |
Serious Adverse Events |
||
| Bortezomib and Doxorubicin | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/4 (0%) | |
Other (Not Including Serious) Adverse Events |
||
| Bortezomib and Doxorubicin | ||
| Affected / at Risk (%) | # Events | |
| Total | 4/4 (100%) | |
| Blood and lymphatic system disorders | ||
| Hemoglobin | 1/4 (25%) | 2 |
| Leukocytes (total WBC) | 1/4 (25%) | 1 |
| Neutrophils/granulocytes (ANC/AGC) | 2/4 (50%) | 2 |
| Gastrointestinal disorders | ||
| Anorexia | 2/4 (50%) | 3 |
| Constipation | 4/4 (100%) | 5 |
| Diarrhea | 2/4 (50%) | 2 |
| Heartburn/dyspepsia | 1/4 (25%) | 1 |
| Mucositis/stomatitis (functional/symptomatic) - Oral cavity | 1/4 (25%) | 2 |
| Nausea | 4/4 (100%) | 6 |
| General disorders | ||
| Fatigue (asthenia, lethargy, malaise) | 3/4 (75%) | 5 |
| Insomnia | 1/4 (25%) | 1 |
| Pain | 4/4 (100%) | 9 |
| Sweating (diaphoresis) | 1/4 (25%) | 1 |
| Infections and infestations | ||
| Infection with normal ANC or Grade 1 or 2 neutrophils - Ungual (nails) | 1/4 (25%) | 1 |
| Infection with normal ANC or Grade 1 or 2 neutrophils - Vagina | 1/4 (25%) | 1 |
| Metabolism and nutrition disorders | ||
| Albumin, serum-low (hypoalbuminemia) | 1/4 (25%) | 1 |
| Glucose, serum-high (hyperglycemia) | 1/4 (25%) | 1 |
| Nervous system disorders | ||
| Dizziness | 2/4 (50%) | 2 |
| Mood alteration: Depression | 1/4 (25%) | 1 |
| Neuropathy: cranial - CN V Motor-jaw muscles; Sensory-facial | 1/4 (25%) | 1 |
| Neuropathy: sensory | 3/4 (75%) | 5 |
| Skin and subcutaneous tissue disorders | ||
| Hair loss/alopecia (scalp or body) | 3/4 (75%) | 3 |
| Nail changes | 1/4 (25%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Dr. Anne Traynor |
|---|---|
| Organization | University of Wisconsin Carbone Cancer Center |
| Phone | 608-262-5092 |
| amt@medicine.wisc.edu |
- 2004-0130
- CO04101
- A534260
- SMPH/MEDICINE