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

NCT02216149 | Terminated Phase 2

• 2 other identifiers: HUS-01/20132013-003976-11
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• Frequency of coronary artery dysfunction

  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.

  3 months

Secondary Outcomes (5)

• Coronary artery blood flow rate

  3 months

• Cardiac arrythmias during 24-hour electrocardiogram registration

  3 months

• Adverse events between the allocation groups

  3 months

• Response to chemotherapy

  3 months

• Survival status

  12 months

Study Arms (2)

S-1 plus oxaliplatin (SOX)

EXPERIMENTAL

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

Drug: S-1; Drug: Oxaliplatin

Oxaliplatin plus capecitabine (XELOX)

ACTIVE COMPARATOR

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

Drug: Capecitabine; Drug: Oxaliplatin

Interventions

S-1 DRUG

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

Also known as: Teysuno, tegafur/gimeracil/oteracil

S-1 plus oxaliplatin (SOX)

Capecitabine DRUG

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

Also known as: Xeloda

Oxaliplatin plus capecitabine (XELOX)

Oxaliplatin DRUG

Oxaliplatin 130 mg/m2 D1 every 3 weeks

Also known as: Eloxatin

Oxaliplatin plus capecitabine (XELOX); S-1 plus oxaliplatin (SOX)

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Heikki Joensuu: lead

Study Sites (1)

Helsinki University Central Hospital

Helsinki, 00029, Finland

Location

MeSH Terms

Conditions

Esophageal Neoplasms; Stomach Neoplasms; Colonic Neoplasms; Rectal Neoplasms; Gastrointestinal Neoplasms

Interventions

S 1 (combination); tegafur-gimeracil-oteracil; Capecitabine; Oxaliplatin

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Stomach Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Coordination Complexes; Organic Chemicals

Study Officials

• Heikki Joensuu, MD

  Helsinki University Central Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD, professor

Study Record Dates

• First Submitted: August 7, 2014
• First Posted: August 13, 2014
• Study Start: January 1, 2015
• Primary Completion: August 1, 2018
• Study Completion: August 1, 2018
• Last Updated: August 28, 2018

Record last verified: 2018-08

Locations

FI (1)