Phase II Trial of Capecitabine in Combination With Fulvestrant for Postmenopausal Women With Hormone Receptor Positive Metastatic Breast Cancer
Overview
- Phase
- Phase 2
- Intervention
- capecitabine
- Conditions
- Metastatic Breast Cancer
- Sponsor
- Accelerated Community Oncology Research Network
- Enrollment
- 41
- Locations
- 10
- Primary Endpoint
- Time to Progression (TTP)
- Status
- Completed
- Last Updated
- 13 years ago
Overview
Brief Summary
The purpose of this study is to determine if the combination of continuous daily capecitabine with fulvestrant on a loading dose schedule will delay disease progression in metastatic breast cancer (MBC) patients.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Provide written informed consent prior to study-specific screening procedures, with the understanding that the patient has the right to withdraw from the study at any time, without prejudice.
- •At least 18 years of age.
- •Post-menopausal female (ie, amenorrheic for at least 12 months prior to study entry). Post-menopausal status will be confirmed by drawing follicle stimulating hormone (FSH) and estradiol levels if \< 2 years since last menses.
- •Ambulatory outpatient with Eastern Cooperative Oncology Group (ECOG)performance status of 0 to 2 at study entry.
- •Primary tumor human epidermal growth factor receptor 2 (HER-2) negative at study entry.(Investigator discretion will be used in instances of immuno-histochemistry \[IHC\] 2+.)
- •Histologically or cytologically confirmed MBC.
- •Primary tumor and/or metastatic lesion estrogen receptor + and/or progesterone receptor + by IHC.
- •At least one measurable or evaluable(non-measurable) lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria (see Appendix 11.6) which has not been irradiated (i.e., newly arising lesions in previously irradiated areas are accepted). Ascites, pleural effusion, and bone metastases are not considered measurable but are considered evaluable (non-measurable). Minimum indicator lesion size for measurable disease: ≥10 mm measured by spiral computed tomography (CT) or ≥20 mm measured by conventional techniques.
- •Adequate hematologic, renal, and hepatic function.
- •Hematologic values: Neutrophils (ANC) \> 1.5 x 109/L; Platelet count \> 100 x 109/L.
Exclusion Criteria
- •Prior administration of capecitabine.
- •Prior administration of fulvestrant.
- •Prior chemotherapy for metastatic breast cancer.
- •Radiotherapy ≤ 2 weeks prior to registration, except if to a non-target lesion only or single-dose radiation for palliation. NOTE: Prior radiation to a target lesion(s) is permitted only if there has been clear progression of the lesion since radiation was completed.
- •Life expectancy \<3 months.
- •Serious, uncontrolled, concurrent infection(s).
- •Prior unanticipated severe reaction to fluoropyrimidine therapy, or known hypersensitivity to 5-fluorouracil or known dihydropyrimidine dehydrogenase (DPD) deficiency.
- •Treatment for other carcinomas within the last 5 years, except cured non-melanoma skin and treated in-situ cervical cancer or superficial bladder tumors (stage Ta or Tis).
- •Participation in any investigational drug study within 4 weeks preceding the start of study treatment.
- •Clinically significant cardiac disease (e.g., congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmias not well controlled with medication)or myocardial infarction within the last 12 months prior to study entry.
Arms & Interventions
Capecitabine and fulvestrant
Capecitabine will be given on a continuous basis at a total dose of 1500 mg, given as 1000 mg po AM and 500 mg po PM in patients of body weight \< 80 kg, and at a total dose of 2000 mg given as 1000 mg po bid in patients with a body weight of ≥80 kg. Fulvestrant will be given at 500 mg on Day 1 followed by 250 mg on Days 15 and 29, then 250 mg every 28 days.
Intervention: capecitabine
Capecitabine and fulvestrant
Capecitabine will be given on a continuous basis at a total dose of 1500 mg, given as 1000 mg po AM and 500 mg po PM in patients of body weight \< 80 kg, and at a total dose of 2000 mg given as 1000 mg po bid in patients with a body weight of ≥80 kg. Fulvestrant will be given at 500 mg on Day 1 followed by 250 mg on Days 15 and 29, then 250 mg every 28 days.
Intervention: fulvestrant
Outcomes
Primary Outcomes
Time to Progression (TTP)
Time Frame: TTP was measured from day 1 of treatment until time of progression (assessed every 8 weeks), up to 29 months.
Time to progression is defined as the time from treatment start until objective tumor progression. Progression is defined per Response Evaluation Criteria in Solid Tumors (RECIST)v1.0 guidelines as a measurable increase in the smallest diameter of any target lesion, progression of existing non-target lesions, or the appearance of 1 or more new lesions. The median time to progression is the parameter used to describe TTP.
Progression-free Survival (PFS)
Time Frame: PFS was measured from day 1 of treatment until time of progression (assessed every 8 weeks) or death, whichever came first, up to 32.5 months.
Disease progression was determined through radiology imaging measurements and by clinical or symptomatic progression during or after treatment. Progression is defined per RECIST v1.0 guidelines as a measurable increase in the smallest diameter of any target lesion, progression of existing non-target lesions, or the appearance of 1 or more new lesions.
Secondary Outcomes
- Best Overall Response(Response to treatment was assessed after every 8 weeks of treatment)
- Overall Response Rate(Response to treatment was assessed after every 8 weeks of treatment)
- Clinical Benefit Rate(Response to treatment was assessed after every 8 weeks of treatment)
- Patients Experiencing Severe Symptom Burden (Physical Symptoms)(The questionnaire was administered on day 1 of every cycle (approximately every 4 weeks) during study treatment.)
- Patients Experiencing Severe Symptom Burden (Psychiatric Symptoms)(The questionnaire was administered on day 1 of every cycle (approximately every 4 weeks) during study treatment.)
- Patients Experiencing Severe Symptom Burden (Physical Functioning)(The questionnaire was administered on day 1 of every cycle (approximately every 4 weeks) during study treatment.)