FluoHeart: Effects of S-1 and Capecitabine on Coronary Artery Blood Flow

Sponsor

Heikki Joensuu (Other)

Overall Status

Terminated

CT.gov ID

NCT02216149

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Esophagus Cancer Stomach Cancer Small Bowel Cancer Colon Cancer Rectum Cancer	Drug: S-1 Drug: Capecitabine Drug: Oxaliplatin	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

20 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Jan 1, 2015

Actual Primary Completion Date :

Aug 1, 2018

Actual Study Completion Date :

Aug 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: S-1 plus oxaliplatin (SOX) Oxaliplatin 130 mg/m2 d. 1 followed by oral S-1 25 mg/m2/day BID d1-14.	Drug: S-1 S-1 25 mg/m2/day BID d1-14, oxaliplatin injection 130 mg/m2 D1 every 3 weeks Other Names: Teysuno tegafur/gimeracil/oteracil Drug: Oxaliplatin Oxaliplatin 130 mg/m2 D1 every 3 weeks Other Names: Eloxatin
Active Comparator: Oxaliplatin plus capecitabine (XELOX) Intravenous oxaliplatin 130 mg/m2 d.1 followed by oral capecitabine 2000 mg/m2/day divided in 2 daily doses d1-14.	Drug: Capecitabine capecitabine 2000 mg/m2/day divided in 2 daily doses d1-14, oxaliplatin injection 130 mg/m2 D1 every 3 weeks Other Names: Xeloda Drug: Oxaliplatin Oxaliplatin 130 mg/m2 D1 every 3 weeks Other Names: Eloxatin

Arm

Intervention/Treatment

Experimental: S-1 plus oxaliplatin (SOX)

Oxaliplatin 130 mg/m2 d. 1 followed by oral S-1 25 mg/m2/day BID d1-14.

Drug: S-1

S-1 25 mg/m2/day BID d1-14, oxaliplatin injection 130 mg/m2 D1 every 3 weeks

Other Names:

Teysuno

tegafur/gimeracil/oteracil

Drug: Oxaliplatin

Oxaliplatin 130 mg/m2 D1 every 3 weeks

Other Names:

Eloxatin

Active Comparator: Oxaliplatin plus capecitabine (XELOX)

Intravenous oxaliplatin 130 mg/m2 d.1 followed by oral capecitabine 2000 mg/m2/day divided in 2 daily doses d1-14.

Drug: Capecitabine

capecitabine 2000 mg/m2/day divided in 2 daily doses d1-14, oxaliplatin injection 130 mg/m2 D1 every 3 weeks

Other Names:

Xeloda

Drug: Oxaliplatin

Oxaliplatin 130 mg/m2 D1 every 3 weeks

Other Names:

Eloxatin

Outcome Measures

Primary Outcome Measures

Frequency of coronary artery dysfunction [3 months]
The frequency of subclinical coronary artery dysfunction is as assessed by comparing the coronary flow reserve during chemotherapy with the baseline coronary flow reserve, and the coronary flow response to a cold pressor test.

Secondary Outcome Measures

Coronary artery blood flow rate [3 months]
The coronary artery blood flow rate is measured with ultrasound. The rates are compared with the baseline and between the groups.
Cardiac arrythmias during 24-hour electrocardiogram registration [3 months]
Cardiac arrythmias detected with Holter cardiac recording.
Adverse events between the allocation groups [3 months]
by CTCAE.4
Response to chemotherapy [3 months]
by RECIST 1.1
Survival status [12 months]
Survival from the first dose of study medication to study completion