Clinical trial NCT02595320: Capecitabine in Metastatic Breast and GI Cancers
Official title: Randomized Open-label Trial of Dose Dense, Fixed Dose Capecitabine Compared to Standard Dose Capecitabine in Metastatic Breast Cancer and Advanced/Metastatic Gastrointestinal Cancers.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Breast Cancer
Gastrointestinal Cancer
Keywords: breast, gastrointestinal,capecitabine, cancer, metastatic
Lead sponsor: University of Kansas Medical Center
Sponsor class: OTHER
First posted: 2015-11-03
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Twelve-week Progression Free Survival (cohort 1 only)
timeFrame: 12 weeks from the date of registration into the study
Secondary outcomes:
measure: Grade 3 or higher toxicity (cohorts 1 and 2)
timeFrame: From Day 1 of treatment, throughout treatment, up to 2 years from Day 1 of treatment
Other outcomes:
measure: Objective response rate (cohorts 1 and 2)
timeFrame: From Day 1 of treatment, throughout treatment, up to 2 years from Day 1 of treatment
Locations:
city: Fairway
country: United States
facility: University of Kansas Cancer Center - CRC
state: Kansas
city: Garden City
country: United States
facility: St. Catherine Hospital - Central Care Cancer Center
state: Kansas
city: Great Bend
country: United States
facility: Heartland Cancer Center - Central Care Cancer Center
state: Kansas
city: Hays
country: United States
facility: Hays Medical Center Dreiling-Schmidt Cancer Institute
state: Kansas
city: Kansas City
country: United States
facility: University of Kansas Cancer Center - West
state: Kansas
city: Olathe
country: United States
facility: Olathe Medical Center
state: Kansas
city: Overland Park
country: United States
facility: University of Kansas Cancer Center - Overland Park
state: Kansas
city: Pittsburg
country: United States
facility: Via Christi Cancer Center
state: Kansas
city: Salina
country: United States
facility: Salina Regional Health
state: Kansas
city: Topeka
country: United States
facility: St. Francis Comprehensive Cancer Center
state: Kansas
city: Westwood
country: United States
facility: University of Kansas Cancer Center - Westwood
state: Kansas
city: Kansas City
country: United States
facility: Truman Medical Center
state: Missouri
city: Kansas City
country: United States
facility: University of Kansas Cancer Center - South
state: Missouri
city: Kansas City
country: United States
facility: University of Kansas Cancer Center - North
state: Missouri
city: Lee's Summit
country: United States
facility: University of Kansas Cancer Center - Lee's Summit
state: Missouri
Study officials:
affiliation: University of Kansas Cancer Center - CRC
name: Qamar Khan, MD
role: PRINCIPAL_INVESTIGATOR
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