Capecitabine in Metastatic Breast and GI Cancers

Study Overview
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Brief Summary
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The purpose of this study is compare different doses of capecitabine to see if one is better than the other in terms of efficacy and toxicity.

Detailed Description
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Goals of treatment of metastatic breast cancer remain largely comfort care. However, there has been improvement in median survival among women with metastatic disease over the last two decades, mainly due to availability of more effective agents. Women are now living longer with metastatic disease and are on therapy for longer periods of time. Therefore, it is increasingly important for effective therapies to be associated with less toxicity so that women can enjoy a better overall quality of life. Similar to breast cancer, goals of treatment of various GI malignancies (including metastatic colorectal cancer, metastatic gastric and esophageal cancers, and unresectable or metastatic pancreatic cancer and cholangiocarcinoma) are largely comfort care and it is important to minimize toxicity from therapy during the treatment for metastatic disease. Capecitabine is a unique chemotherapeutic agent for two reasons. It is the only oral chemotherapy drug available to treat breast and GI malignancies, making it convenient for patients. In addition, whereas all other cytotoxic chemotherapy agents can be administered for only a few months at a time because of development of cumulative toxicities, capecitabine can be continued for many months to years if toxicities can be managed. However the optimal dosing schedule of capecitabine is not known. This is the basis for the proposed randomized phase II trial, to compare the efficacy and tolerability of capecitabine 1500 milligrams (mg) twice a day (BID), 7 days on and 7 days off schedule to capecitabine 1250 milligrams/meters squared (mg/m2) BID, 14 days on and 7 days off) or 1000 mg/m2 BID, 14 days on and 7 days off, in women with metastatic breast cancer or patients with advanced/metastatic GI cancer.

Official Title
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Randomized Open-label Trial of Dose Dense, Fixed Dose Capecitabine Compared to Standard Dose Capecitabine in Metastatic Breast Cancer and Advanced/Metastatic Gastrointestinal Cancers.

Conditions
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Breast Cancer, Gastrointestinal Cancer

Intervention / Treatment
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* Drug: Capecitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women with metastatic breast cancer OR men and women with metastatic gastrointestinal (GI) cancer There is no limit to the number of prior chemotherapy or endocrine therapy regimens received. Use of a previous fluoropyrimidine-containing regimen in advanced / metastatic setting is permitted as long as the subject discontinued the regimen for reasons other than progression. No restriction on the use of fluoropyrimidine-containing regimen in the neoadjuvant or adjuvant setting For metastatic colorectal cancers, patients starting maintenance capecitabine after a course of oxaliplatin or irinotecan based chemotherapy are eligible. Measurable or non-measurable disease per RECIST criteria 1.1 Must have completed prior chemotherapy or radiation therapy at least 2 weeks prior to registration Pathologic confirmation of respective malignancies. Biopsy of metastatic disease is preferred but not mandatory. Performance Status: Eastern Cooperative Oncology Group (ECOG) Performance Score (PS) 0-2 Adequate organ and marrow function as defined below: Absolute neutrophil count ≥ 1,000/ microLiter (uL) hemoglobin ≥ 7 g/L platelets ≥ 50,000/uL total bilirubin ≤ 2 X the Institutional Upper Limit of Normal (IULN) o Aspartate Aminotransferase (AST) ( Serum Glutamic Oxaloacetic Transaminase [SGOT]) ≤ 5 X IULN Alanine Aminotransferase (ALT) (Serum Pyruvic Glutamic Transaminase [SPGT]) ≤ 5 X IULN creatinine clearance > 50 milliliters per minute (ml/min) Women of childbearing potential must agree to use adequate contraception. Subjects may have previously treated brain or Central Nervous System (CNS) metastasis with radiation completed at least 2 weeks prior to registration. Prior radiation to places other than CNS disease must be completed at least 14 days prior to registration. Any number of prior radiation therapy regimens is allowed provided all toxicity of prior therapy is resolved to grade 1 or less. Life expectancy of >3 months Exclusion Criteria: Patient has used Capecitabine in a past regimen for metastatic disease. Patient is currently using, or planning to use another investigational agent. Patient with known Dihydropyrimidine Dehydrogenase (DPD) deficiency Patient has symptomatic brain or CNS metastases. Patient has leptomeningeal disease Patient is pregnant or nursing Subjects must have no barriers to taking oral medications, for example uncontrolled nausea, vomiting, diarrhea at baseline, lack of physical integrity of the upper gastrointestinal tract, or malabsorption syndrome. No recent (≤ 3months) of partial or complete bowel obstruction unless surgically corrected.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br>capecitabine, 1500 mg, twice a day for 7 days on then 7 days off | Drug: Capecitabine<br>* Capecitabine will be given to participants in Arm A at 1500 mg PO BID for 7 days, followed by a 7 day rest (7-7). Capecitabine will be given to participants in group B at 1250 mg/m2 OR 1000 mg/m2 PO BID for 14 days, followed by a 7 day rest (14-7).<br>* Other names: Xeloda®;|
| Active Comparator: Group B<br>capecitabine, 1250 mg/m2 OR 1000 mg/m2, twice a day for 14 days on then 7 days off | Drug: Capecitabine<br>* Capecitabine will be given to participants in Arm A at 1500 mg PO BID for 7 days, followed by a 7 day rest (7-7). Capecitabine will be given to participants in group B at 1250 mg/m2 OR 1000 mg/m2 PO BID for 14 days, followed by a 7 day rest (14-7).<br>* Other names: Xeloda®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Twelve-week Progression Free Survival (cohort 1 only) | As the percentage of patients with progression from the date of registration to 12 weeks from that date | 12 weeks from the date of registration into the study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Grade 3 or higher toxicity (cohorts 1 and 2) | Percentage of patients having grade 3 or higher toxicity from the date of first treatment dose during the trial therapy to patient develops Grade 3 or higher toxicity. | From Day 1 of treatment, throughout treatment, up to 2 years from Day 1 of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breast, gastrointestinal,capecitabine, cancer, metastatic