Capecitabine in Metastatic Breast and GI Cancers

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.

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.