Capecitabine in Treating Patients with Metastatic Breast Cancer or Advanced / Metastatic Gastrointestinal Cancers

This randomized phase II trial studies the side effects of capecitabine and how well it works when it is given dose-dense, fixed-dose as compared to standard dose in treating patients with breast cancer or gastrointestinal cancer that has spread from where it started to other places in the body or gastrointestinal cancer that has spread to other places in the body and usually cannot be cured or controlled with treatment. Drugs used in chemotherapy, such as capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Inclusion Criteria

• Ability to understand and the willingness to sign a written informed consent
• Women with metastatic breast cancer who are eligible for capecitabine monotherapy; for HER2 positive breast cancer, concurrent trastuzumab is allowed OR
• Patients (both male and female) with advanced/metastatic GI cancers eligible for capecitabine monotherapy, including metastatic colorectal cancer, metastatic gastric and esophageal cancers, and unresectable or metastatic pancreatic cancer and cholangiocarcinoma, including gall bladder carcinoma, concurrent trastuzumab is allowed for HER2 positive gastric/esophageal cancer
• 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
• There is 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 Response Evaluation Criteria in Solid Tumors (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 status (PS) 0-2
• Absolute neutrophil count >= 1,000/uL
• Hemoglobin >= 7 g/L
• Platelets >= 50,000/uL
• Total bilirubin =< 2 X institutional upper limit of normal (IULN)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 5 X IULNl
• Creatinine clearance > 50 ml/min
• Women of child-bearing potential and men with partners of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 30 days following completion of therapy; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; a woman of child-bearing potential is any female (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: * Has not undergone a hysterectomy or bilateral oophorectomy; OR * Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)
• 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 (=< 3 months) of partial or complete bowel obstruction unless surgically corrected

PRIMARY OBJECTIVES:

I. To compare the efficacy and tolerability of fixed-dose capecitabine on a 7-7 schedule (1500 mg twice daily [BID], 7 days on and 7 days off) to the Food and Drug Administration (FDA) recommended dose and schedule (1250 mg/m^2 BID, 14 days on and 7 days off) or 1000 mg/m2 BID, 14 days on and 7 days off in metastatic breast cancer in advanced/metastatic gastrointestinal (GI) cancers.

OUTLINE: Patients are randomized 1 of 2 treatment arms.

ARM I: Patients receive capecitabine orally (PO) BID for 7 days followed by a 7 day rest. Treatment continues in the absence of disease progression and unacceptable toxicity.

ARM II: Patients receive capecitabine PO BID for 14 days followed by a 7 day rest. Treatment continues in the absence of disease progression and unacceptable toxicity.

After completion of the study treatment, patients are followed up at 30 days and then every 6 months for 2 years.

Lead Organization
University of Kansas Cancer Center

Principal Investigator
Qamar Jamal Khan