Phase II Trial of Capecitabine With Fulvestrant for Postmenopausal Women With Hormone Receptor Positive Metastatic Breast Cancer

Metastatic Breast Cancer Clinical Trial

Official title:

Phase II Trial of Capecitabine in Combination With Fulvestrant for Postmenopausal Women With Hormone Receptor Positive Metastatic Breast Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00534417
• Other study ID #: ALSSMBC0606
• Status: Completed
• Phase: Phase 2
• First received: September 20, 2007
• Last updated: December 28, 2012
• Start date: October 2007
• Est. completion date: September 2011

Study information

• Verified date: December 2012
• Source: Accelerated Community Oncology Research Network
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 41
• Est. completion date: September 2011
• Est. primary completion date: September 2011
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

• Renal function: estimated creatinine clearance > 30 mL/min as calculated with Cockcroft-Gault equation.

• Note: In patients with moderate renal impairment (calculated creatinine clearance 30 to 50 mL/min) at baseline, a dose reduction to (-1) of the capecitabine starting dose is required.

• Serum bilirubin < 1.5 x upper limit normal (ULN).

• Alanine transaminase (ALT) or aspartate transaminase (AST) < 2.5 x ULN (or < 5 x ULN in the case of liver metastases).

• Alkaline phosphatase < 2.5 x ULN (or < 5 x ULN in the case of liver metastases or < 10 x ULN in the case of bone disease).

• International normalization ratio (INR) < 1.6.

• Must have = 1 prior regimen of endocrine therapy for metastatic breast cancer. This would include patients who have a recurrence while on adjuvant hormone therapy OR have first recurrence after adjuvant hormone therapy OR progressed after first line hormone therapy for metastatic breast cancer OR treatment naïve patients who present with metastatic breast cancer.

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.

• Active brain metastases. Patients with neurological symptoms must undergo a CT scan or magnetic resonance imaging (MRI) of the brain to exclude active brain metastasis. NOTE: Patients with treated brain metastases are eligible provided they have no evidence of disease and are off definitive therapy (including steroids) = 3 months prior to study entry.

• Central nervous system (CNS) disorders or psychiatric disability judged by the investigator to be clinically significant, precluding informed consent, or interfering with compliance of oral drug intake.

• Known human immunodeficiency virus or chronic hepatitis B or C.

• Other serious uncontrolled medical conditions that the investigator feels might compromise study participation.

• Major surgery within 4 weeks of the start of study treatment, without complete recovery.

• Lack of physical integrity of the upper GI tract or malabsorption syndrome.

• Known, existing uncontrolled coagulopathy.

• Any of the following laboratory values:

• Abnormal hematologic values (neutrophils [ANC]: <1.5 × 109/L, platelet count:

<100 × 109/L)

• Impaired renal function (estimated creatinine clearance: <30 mL/min as calculated with Cockcroft-Gault equation). Note: In patients with moderate renal impairment (calculated creatinine clearance: 30 to 50 mL/min) at baseline, a dose reduction to (-1) of the capecitabine starting dose is required.

• Serum bilirubin >1.5 × upper normal limit (ULN).

• Alanine transaminase (ALT) or aspartate transaminase (AST) >2.5 × ULN (or >5 × ULN in the case of liver metastases).

• Alkaline phosphatase > 2.5 × ULN (or >5 × ULN in the case of liver metastases or >10 × ULN in the case of bone disease).

• International normalization ratio (INR) >1.6.

• History of:

• Bleeding diathesis,(ie, disseminated intravascular coagulation [DIC], clotting factor deficiency) or

• Long-term anticoagulant therapy,(other than antiplatelet therapy and warfarin 1 mg qd for port prophylaxis).

• History of hypersensitivity to active or inactive excipients of fulvestrant (ie, castor oil or Mannitol).

• Unwillingness to give written informed consent.

• Unwillingness to participate or inability to comply with the protocol for the duration of the study.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Neoplasms
• Metastatic Breast Cancer

Intervention

Drug:
• capecitabine
Capecitabine will be given on a continuous basis at a total dose of 1500 mg, given as 1000 mg po in the morning (AM) and 500 mg po in the evening (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
Fulvestrant will be given at 500mg on Day 1 followed by 250 mg on Days 15 and 29, then 250mg every 28 days(Q28d).

Locations

Country	Name	City	State
United States	Northeast Georgia Cancer Care	Athens	Georgia
United States	Augusta Oncology Associates	Augusta	Georgia
United States	Hematology Oncology Centers of the Northern Rockies	Billings	Montana
United States	Cancer Specialists of Tidewater	Chesapeake	Virginia
United States	Medical & Surgical Specialists	Galesburg	Illinois
United States	Las Vegas Cancer Center	Henderson	Nevada
United States	The Lancaster Cancer Center, Ltd	Lancaster	Pennsylvania
United States	The West Clinic	Memphis	Tennessee
United States	Advanced Medical Specialties	Miami	Florida
United States	Oncology Specialists	Park Ridge	Illinois

Sponsors (3)

Lead Sponsor	Collaborator
Accelerated Community Oncology Research Network	AstraZeneca, Hoffmann-La Roche

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to Progression (TTP)	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.	TTP was measured from day 1 of treatment until time of progression (assessed every 8 weeks), up to 29 months.	No
Primary	Progression-free Survival (PFS)	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.	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.	No
Secondary	Best Overall Response	Best overall response is defined as the best response across all time points. Response was evaluated via changes from baseline in radiological tumor measurements performed after every two treatment cycles and at the end of treatment or time of progression. Response was evaluated using RECIST version 1.0 guidelines, where complete response (CR) is the disappearance of all target lesions; partial response (PR) is >=30% decrease in the sum of the longest diameter (LD) of target lesions; Stable Disease (SD) is neither sufficient shrinkage in sum of LD of target lesions to be PR nor increase of >=20%; Progressive Disease (PD) is the increase in existing lesions or new lesions.	Response to treatment was assessed after every 8 weeks of treatment	No
Secondary	Overall Response Rate	Overall response rate was defined as the percentage of participants experiencing complete response (CR) and partial response (PR). Response was evaluated via changes from baseline in radiological tumor measurements performed after every two treatment cycles and at the end of treatment or time of progression. Response was evaluated using RECIST version 1.0 guidelines, where complete response (CR) is the disappearance of all target lesions; partial response (PR) is >=30% decrease in the sum of the longest diameter (LD) of target lesions; Stable Disease (SD) is neither sufficient shrinkage in sum of LD of target lesions to be PR nor increase of >=20%; Progressive Disease (PD) is the increase in existing lesions or new lesions.	Response to treatment was assessed after every 8 weeks of treatment	No
Secondary	Clinical Benefit Rate	Clinical benefit rate was defined as the percentage of participants experiencing stable disease (SD) of at least 24 weeks plus complete response (CR) and partial response (PR). Response was evaluated via changes from baseline in radiological tumor measurements performed after every two treatment cycles and at the end of treatment or time of progression. Response was evaluated using RECIST version 1.0 guidelines, where CR is the disappearance of all target lesions; PR is >=30% decrease in the sum of the longest diameter(LD) of target lesions; SD is neither sufficient shrinkage in sum of longest diameter of target lesions to be PR nor increase of >=20%.	Response to treatment was assessed after every 8 weeks of treatment	No
Secondary	Patients Experiencing Severe Symptom Burden (Physical Symptoms)	The subject rates each question about physical symptoms on a scale of 0 through 10, where 0 is not bad and 10 is as bad as possible. Severe symptoms are indicated by a response > or = to 7 on an item.	The questionnaire was administered on day 1 of every cycle (approximately every 4 weeks) during study treatment.	No
Secondary	Patients Experiencing Severe Symptom Burden (Psychiatric Symptoms)	The subject rates each question about psychiatric symptoms on a scale of 0 through 10, where 0 is not bad and 10 is as bad as possible. Severe symptoms are indicated by a response > or = to 7 on an item.	The questionnaire was administered on day 1 of every cycle (approximately every 4 weeks) during study treatment.	No
Secondary	Patients Experiencing Severe Symptom Burden (Physical Functioning)	The subject rates each question about physical functioning on a scale of 0 through 10, where 0 is not bad and 10 is as bad as possible. Severe symptoms are indicated by a response > or = to 7 on an item.	The questionnaire was administered on day 1 of every cycle (approximately every 4 weeks) during study treatment.	No