Breast Cancer
Conditions
Keywords
stage IV breast cancer, recurrent breast cancer
Brief summary
RATIONALE: Drugs used in chemotherapy, such as cyclophosphamide and capecitabine, 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 chemotherapy drug may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving cyclophosphamide together with capecitabine works in treating women with stage IV breast cancer.
Detailed description
OBJECTIVES: * Determine the response rate (complete and partial, confirmed and unconfirmed) in women with stage IV breast cancer treated with oral cyclophosphamide and oral capecitabine. * Determine the progression-free survival and overall survival of patients treated with this regimen. * Determine the toxicity of this regimen in these patients. * Determine the quality of life of patients treated with this regimen. OUTLINE: This is a multicenter study. Patients receive oral cyclophosphamide once daily on days 1-14 and oral capecitabine twice daily on days 8-21. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline and then at weeks 7, 13, 19, and 25. After completion of study treatment, patients are followed every 3 months for up to 2 years. PROJECTED ACCRUAL: A total of 96 patients will be accrued for this study within 4 years.
Interventions
DRUGcapecitabine
DRUGcyclophosphamide
Sponsors
National Cancer Institute (NCI)
SWOG Cancer Research Network
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically or cytologically confirmed stage IV breast cancer * Metastatic disease (M1) OR multiple sites of new disease that is clinically obvious metastatic disease (i.e., multiple sites of new osseous disease) * Meets 1 of the following criteria: * Measurable disease * Non-measurable disease * MUC-1 antigen level \> 2 times upper limit of normal AND level has increased by 1.5 times * Must have documented MUC-1 antigen level * Either cancer antigen (CA) 15-3 or CA 27-29 allowed * Must have received at least 1 prior hormonal therapy for metastatic disease (estogen receptor-positive patients only) * No symptomatic brain or CNS metastases * Previously treated brain or CNS metastasis allowed provided radiotherapy was completed ≥ 8 weeks before study entry * Hormone receptor status: * Not specified PATIENT CHARACTERISTICS: Age * 18 and over Sex * Female Menopausal status * Not specified Performance status * Zubrod 0-2 Life expectancy * Not specified Hematopoietic * No known existing uncontrolled coagulopathy Hepatic * Not specified Renal * Creatinine clearance \> 40 mL/min Cardiovascular * No congestive heart failure * No symptomatic coronary artery disease * No cardiac arrhythmia not well controlled with medication * No myocardial infarction within the past 12 months * No other clinically significant cardiac disease Gastrointestinal * Able to take oral medication * No uncontrolled nausea, vomiting, or diarrhea * No lack of physical integrity of the upper gastrointestinal tract * No malabsorption syndrome Other * Not pregnant or nursing * Fertile patients must use effective contraception * No active infection requiring systemic therapy * No prior severe reaction to fluoropyrimidines * No known sensitivity to fluorouracil * No known dihydropyrimidine dehydrogenase deficiency * No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix PRIOR CONCURRENT THERAPY: Biologic therapy * No concurrent immunotherapy or biologic therapy for breast cancer * No concurrent gene therapy for breast cancer * No concurrent filgrastim (G-CSF) Chemotherapy * At least 14 days since prior chemotherapy and recovered * No more than 2 prior chemotherapy regimens for metastatic disease * No prior capecitabine for metastatic disease * No prior oral cyclophosphamide for metastatic disease * Prior IV cyclophosphamide allowed * No other concurrent chemotherapy for breast cancer Endocrine therapy * See Disease Characteristics * No concurrent hormonal therapy for breast cancer Radiotherapy * See Disease Characteristics * At least 14 days since prior radiotherapy to non-CNS disease sites and recovered * No concurrent radiotherapy for breast cancer Surgery * Not specified Other * Concurrent bisphosphonates allowed * No concurrent full-dose warfarin * Concurrent prophylactic warfarin (≤ 1 mg/day) to maintain port patency allowed * No other concurrent antineoplastic therapy for breast cancer
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate (Complete and Partial, Confirmed and Unconfirmed) | Patients assessed at least every six weeks while on protocol treatment | Complete Response (CR) is complete disappearance of all measurable and non-measurable disease. No new lesions, no disease related symptoms. Normalization of markers and other abnormal lab values. Partial Response (PR) is greater than or equal to 30% decrease under baseline of the sum of longest diameters of all target measurable lesions. No unequivocal progression of non-measurable disease. No new lesions. Confirmation of CR or PR means a repeat scan at least 4 weeks apart documented before progression or symptomatic deterioration. Progression is 20% increase in sum of longest diameters of target measurable lesions over smallest sum observed and/or unequivocal progression of non-measurable disease and/or appearance of new lesion/site or death due to disease without prior documentation of progression and without symptomatic deterioration. Symptomatic deterioration is global deterioration of health status requiring discontinuation of treatment without objective evidence of progression. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival and Overall Survival | two years | Progression-Free Survival: From date of registration to time of first documentation of progression or symptomatic deterioration, or death due to any cause. Patients last known to be alive and progression-free are censored at last date of contact. Overall Survival: From date of registration to date of death due to any cause. Patients last known to be alive are censored at last date of contact. Progression is 20% increase in sum of longest diameters of target measurable lesions over smallest sum observed and/or unequivocal progression of non-measurable disease and/or appearance of new lesion/site or death due to disease without prior documentation of progression and without symptomatic deterioration. Symptomatic deterioration is global deterioration of health status requiring discontinuation of treatment without objective evidence of progression. |
| Toxicity | Patients assessed after each 21-day cycle for 8 cycles (24 weeks of treatment) | Number of patients for whom Grade 3 or higher toxicity observed during treatment. Only adverse events that are possibly, probably or definitely related to study drug are reported. |
Countries
United States
Participant flow
Recruitment details
Between 8/15/2005 and 9/1/2007, 112 patients were registered from 26 SWOG institutions who obtained Institutional Review Board (IRB) approval for the study.
Participants by arm
| Arm | Count |
|---|---|
| Cyclophosphamide and Capecitabine cyclophosphamide orally days 1-14 and capecitabine orally days 15-21 for 8 cycles of 21 days each | 96 |
| Total | 96 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 6 |
| Overall Study | Death | 1 |
| Overall Study | Ineligible | 16 |
| Overall Study | M.D. decision | 2 |
| Overall Study | Patient refusal | 1 |
| Overall Study | Progression | 46 |
Baseline characteristics
| Characteristic | Cyclophosphamide and Capecitabine |
|---|---|
| Age Continuous | 59.7 years |
| Sex: Female, Male Female | 96 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 92 / 95 |
| serious Total, serious adverse events | 4 / 95 |
Outcome results
Primary
Response Rate (Complete and Partial, Confirmed and Unconfirmed)
Complete Response (CR) is complete disappearance of all measurable and non-measurable disease. No new lesions, no disease related symptoms. Normalization of markers and other abnormal lab values. Partial Response (PR) is greater than or equal to 30% decrease under baseline of the sum of longest diameters of all target measurable lesions. No unequivocal progression of non-measurable disease. No new lesions. Confirmation of CR or PR means a repeat scan at least 4 weeks apart documented before progression or symptomatic deterioration. Progression is 20% increase in sum of longest diameters of target measurable lesions over smallest sum observed and/or unequivocal progression of non-measurable disease and/or appearance of new lesion/site or death due to disease without prior documentation of progression and without symptomatic deterioration. Symptomatic deterioration is global deterioration of health status requiring discontinuation of treatment without objective evidence of progression.
Time frame: Patients assessed at least every six weeks while on protocol treatment
Population: Eligible patients with RECIST measurable disease
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cyclophosphamide and Capecitabine | Response Rate (Complete and Partial, Confirmed and Unconfirmed) | 29 participants |
Secondary
Progression-free Survival and Overall Survival
Progression-Free Survival: From date of registration to time of first documentation of progression or symptomatic deterioration, or death due to any cause. Patients last known to be alive and progression-free are censored at last date of contact. Overall Survival: From date of registration to date of death due to any cause. Patients last known to be alive are censored at last date of contact. Progression is 20% increase in sum of longest diameters of target measurable lesions over smallest sum observed and/or unequivocal progression of non-measurable disease and/or appearance of new lesion/site or death due to disease without prior documentation of progression and without symptomatic deterioration. Symptomatic deterioration is global deterioration of health status requiring discontinuation of treatment without objective evidence of progression.
Time frame: two years
Population: All eligible patients
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cyclophosphamide and Capecitabine | Progression-free Survival and Overall Survival | PFS | 5.9 months |
| Cyclophosphamide and Capecitabine | Progression-free Survival and Overall Survival | OS | 18.8 months |
Secondary
Toxicity
Number of patients for whom Grade 3 or higher toxicity observed during treatment. Only adverse events that are possibly, probably or definitely related to study drug are reported.
Time frame: Patients assessed after each 21-day cycle for 8 cycles (24 weeks of treatment)
Population: Eligible patients evaluable for toxicity assessment (one eligible patient who was removed from treatment due to disease progression less than 3 weeks after registration is not evaluable for toxicity assessment)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cyclophosphamide and Capecitabine | Toxicity | ALT, SGPT (serum glutamic pyruvic transaminase) | 1 Participants |
| Cyclophosphamide and Capecitabine | Toxicity | Alkaline phosphatase | 1 Participants |
| Cyclophosphamide and Capecitabine | Toxicity | Dehydration | 2 Participants |
| Cyclophosphamide and Capecitabine | Toxicity | Diarrhea | 2 Participants |
| Cyclophosphamide and Capecitabine | Toxicity | Dyspnea (shortness of breath) | 1 Participants |
| Cyclophosphamide and Capecitabine | Toxicity | Fatigue (asthenia, lethargy, malaise) | 2 Participants |
| Cyclophosphamide and Capecitabine | Toxicity | Febrile neutropenia | 1 Participants |
| Cyclophosphamide and Capecitabine | Toxicity | Hemoglobin | 1 Participants |
| Cyclophosphamide and Capecitabine | Toxicity | Leukocytes (total WBC) | 15 Participants |
| Cyclophosphamide and Capecitabine | Toxicity | Lymphopenia | 13 Participants |
| Cyclophosphamide and Capecitabine | Toxicity | Mood alteration - depression | 1 Participants |
| Cyclophosphamide and Capecitabine | Toxicity | Nausea | 1 Participants |
| Cyclophosphamide and Capecitabine | Toxicity | Neuroendocrine: ADH secretion abnormality | 1 Participants |
| Cyclophosphamide and Capecitabine | Toxicity | Neutrophils/granulocytes (ANC/AGC) | 7 Participants |
| Cyclophosphamide and Capecitabine | Toxicity | Platelets | 1 Participants |
| Cyclophosphamide and Capecitabine | Toxicity | Potassium, serum-low (hypokalemia) | 1 Participants |
| Cyclophosphamide and Capecitabine | Toxicity | Pruritus/itching | 1 Participants |
| Cyclophosphamide and Capecitabine | Toxicity | Rash/desquamation | 1 Participants |
| Cyclophosphamide and Capecitabine | Toxicity | Rash: hand-foot skin reaction | 7 Participants |
| Cyclophosphamide and Capecitabine | Toxicity | Sodium, serum-low (hyponatremia) | 1 Participants |
| Cyclophosphamide and Capecitabine | Toxicity | Thrombosis/thrombus/embolism | 2 Participants |
| Cyclophosphamide and Capecitabine | Toxicity | Weight loss | 1 Participants |