Clinical trial NCT02216149: Effects of S-1 and Capecitabine on Coronary Artery Blood Flow
Official title: Effects of S-1 and Capecitabine in Combination With Oxaliplatin on the Coronary Artery Blood Flow in Patients Metastatic Gastrointestinal Tract Adenocarcinoma: a Randomized Phase II Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Esophagus Cancer
Stomach Cancer
Small Bowel Cancer
Colon Cancer
Rectum Cancer
Keywords: fluoropyrimidine
S-1
Teysuno
oxaliplatin
coronary artery flow
coronary artery dysfunction
gastrointestinal tract cancer
Lead sponsor: Helsinki University Central Hospital
Sponsor class: OTHER
First posted: 2014-08-13
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Fluoropyrimidine chemotherapy agents , such as 5-fluorouracil and capecitabine, are occasionally associated with cardiac toxicity. Clinical fluoropyrimidine cardiotoxicity is infrequent, but subclinical toxicity may be much more common. Cardiac toxicity may be less frequent with S-1 as compared with 5-fluorouracil and capecitabine, but head-to-head comparisons are lacking. The purpose of the study is to compare 2 measures of subclinical coronary artery microvascular dysfunction, the coronary flow reserve and the coronary flow response to a cold pressor test, in a patient population who are being treated for adenocarcinoma of the gastrointestinal tract with one of 2 oxaliplatin-containing regimens, either with oxaliplatin plus S-1 or with oxaliplatin plus capecitabine.

Detailed description: Patients diagnosed with adenocarcinoma of the gastroesophageal tract are randomly assigned to receive two 3-weekly cycles of either XELOX (intravenous oxaliplatin 130 mg/m2 d.1 followed by oral capecitabine 2000 mg/m2/day divided in 2 daily doses d1-14) or SOX (intravenous oxaliplatin 130 mg/m2 d. 1 followed by oral S-1 25 mg/m2/day BID d1-14). A cross-over between the 2 arms is carried out after the first 2 cycles; patients allocated to XELOX will receive 2 cycles of SOX (cycles 3 and 4), and those allocated to SOX will receive XELOX (cycles 3 and 4). Monitoring of the coronary artery flow, cardiac arrythmias, cardiac symptoms and blood biochemistry is done at baseline, during each chemotherapy cycle (cycles 1 to 4) and after treatment.Study treatment will continue until all patients have discontinued from treatment or maximum 24 weeks from the date of the first day of treatment, whichever occurs first. At that point, treatment may continue at the discretion of the Investigator. Each patient will be followed for survival status for a minimum of 12 months after first dose of study medication. Tumor assessments will be performed throughout the study period and analyzed using Response Evaluation Criteria in Solid Tumors (RECIST) criteria (Version 1.1, 2009). Computed tomography (CT) scans will be performed at the end of every 2 cycles. Cardiac assessments will be performed and analyzed using non-invasive transthoracic Doppler echocardiography, 24-h Holter registration, and plasma troponin concentration.

Eligibility criteria: Inclusion Criteria:

* Has given written informed consent.
* Is at least 18 years of age.
* Has advanced or metastatic gastrointestinal tract adenocarcinoma.
* No previous cancer chemotherapy for cancer.
* Measurable or evaluable lesions according to RECIST v1.1 criteria.
* Is able to take medications orally.
* Has ECOG performance status 0 or 1.
* Has a life expectancy of at least 3 months.
* Has adequate organ function.

Exclusion Criteria:

* Cancer considered operable without prior chemotherapy.
* Prior chemotherapy to cancer.
* Previous therapy with fluoropyrimidines or anthracyclines for any indication.
* Inability to swallow tablets.
* Known brain metastasis or leptomeningeal metastasis.
* History of myocardial infarction, coronary stenting/graft.
* History of unstable angina, coronary/peripheral artery bypass graft.
* History of cerebrovascular accident or transient ischemic attack.
* History of pulmonary embolism or deep vein thrombosis.
* Symptomatic congestive heart failure.
* Ongoing cardiac dysrhythmias.
* Patients with any cardiac disease that requires regular medication.
* Hypertensive crisis or severe hypertension that is not controlled.
* Is a pregnant or lactating female.
* The cardiac arterial flow tests cannot be done.

Primary outcomes:
measure: Frequency of coronary artery dysfunction
timeFrame: 3 months
Secondary outcomes:
measure: Coronary artery blood flow rate
timeFrame: 3 months
measure: Cardiac arrythmias during 24-hour electrocardiogram registration
timeFrame: 3 months
measure: Adverse events between the allocation groups
timeFrame: 3 months
measure: Response to chemotherapy
timeFrame: 3 months
measure: Survival status
timeFrame: 12 months
Other outcomes:
Locations:
city: Helsinki
country: Finland
facility: Helsinki University Central Hospital
Study officials:
affiliation: Helsinki University Central Hospital
name: Heikki Joensuu, MD
role: PRINCIPAL_INVESTIGATOR
References: