| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Metastatic gastrointestinal tract adenocarcinoma |
|
| E.1.1.1 | Medical condition in easily understood language |
| Malignant tumor disease arising from gastrointestinal tract (e.g. stomach, intestine) belonging to the adenocarcinoma group of tumors |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 17.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10063916 |
| E.1.2 | Term | Metastatic gastric cancer |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| The frequency of subclinical coronary artery dysfunction, as assessed with the CFR, as compared with the baseline CFR |
|
| E.2.2 | Secondary objectives of the trial |
•The CFR between the chemotherapy groups.
•The coronary flow response to the CPT as compared to the baseline values and between the chemotherapy groups.
•The presence of left ventricle regional wall motion abnormalities or global systolic dysfunction
•Cardiac arrhythmias in Holter registration between the 2 groups and as compared to the baseline.
•Plasma sensitive troponin concentration between the 2 groups and as compared to the baseline.
•Frequency and severity of cardiac symptoms and chest pain during treatment.
•Adverse events (Common Terminology Criteria for Adverse Events [CTCAE] version 4.0) between the 2 treatment groups.
•Response rate of cancer to chemotherapy between the 2 treatment groups (RECIST v. 1.1).
•Patient preference of chemotherapy (assessed at the completion of chemotherapy when ≥ 3 cycles were given)
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1.Has given written informed consent.
2.Is >18 years of age.
3.Has advanced or metastatic gastrointestinal tract adenocarcinoma.
4.No previous cancer chemotherapy for cancer.
5.Measurable or evaluable lesions according to RECIST v1.1 criteria.
6.Is able to take medications orally.
7.Has ECOG performance status 0 or 1 on Cycle 1, Day 1 (see Appendix A).
8.Has a life expectancy of at least 3 months.
9.Serum troponin T or I and creatine phosphokinase (CPK)-MB values < upper limit of normal (ULN) for the institution.
10.Has adequate organ function as defined by the following criteria:
a.Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤2 x ULN; if liver function abnormalities are due to underlying liver metastasis, AST (SGOT) and ALT (SGPT) ≤6 x ULN.
b.Total serum bilirubin of ≤1.5 x ULN.
c.Absolute neutrophil count of ≥1,500/mm3 (i.e., ≥1.5 x 109/L by International Units [IU])
d.Platelet count ≥100,000/mm3 (IU: ≥100 x 109/L) (excluding measurements obtained within 7 days after transfusion).
e.Hemoglobin value of ≥11.0 g/dL.
f.Creatinine < 1.5 x ULN. I creatinine clearance is measured, this should be ≥60 mL/min based on calculated creatinine clearance (Cockcroft-Gault13 formula, see Appendix D) or 24-hour urine collection.
g.Is willing and able to comply with scheduled visits, treatment plan, lab tests and other study procedures
|
|
| E.4 | Principal exclusion criteria |
1.Has had treatment with any of the following within the specified time frame prior to study drug administration:
a.Cancer considered operable without prior chemotherapy.
b.Prior chemotherapy to cancer.
c.Previous therapy with fluoropyrimidines or anthracyclines for any indication.
d.Inability to swallow tablets.
e.Patients with known DPD deficiency.
f.Any investigational agent received either concurrently or within the last4 weeks.
g.Current enrollment in another interventional clinical study.
2.Has a serious illness or medical condition(s) including, but not limited to, the following:
a.Known brain metastasis or leptomeningeal metastasis.
b.Patient with a history of myocardial infarction within the last 6 months, or with a history of coronary surgery or stenting, severe/unstable angina, coronary/peripheral artery bypass graft, cerebrovascular accident or transient ischemic attack, pulmonary embolism, or deep vein thrombosis within the last 12 months.
c.Symptomatic congestive heart failure (New York Heart Association [NYHA] class III or IV (see Appendix E).
d.Ongoing cardiac dysrhythmias (≥Grade 2), atrial fibrillation (any grade), or prolongation of QTc interval (>450 msec for males; >470 msec for females).
e.Patients with any cardiac disease that requires regular medication (medication for vascular diseases such as hypertension is allowed).
f.Hypertensive crisis or severe hypertension that is not controlled.
g.Known acute systemic infection.
h.Chronic nausea, vomiting, or diarrhea considered to be clinically significant in the opinion of the Investigator.
i.≥Grade 1 peripheral neuropathy.
j.Recent hemoptysis, coagulopathy and other bleeding disorders considered by the Investigator to be clinically significant.
k.Known nephrotic syndrome (proteinuria >2 g/24 hours).
l.Known clinically significant interstitial lung disease or pulmonary fibrosis.
m.Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness.
n.Organ allografts with immunosuppressive therapy required.
o.Major surgery within 3 weeks prior to study treatment start, or lack of complete recovery from the effects of surgery.
p.Clinically significant malabsorption syndrome
q.Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the Investigator would make the patient inappropriate for entry into this study.
3.Is receiving concomitant treatment with short-acting nitroglycerins, or one or more of the following drugs that may interact with S-1or capecitabine:
a.Sorivudine, brivudine, uracil, eniluracil, cimetidine, folinate/folinic acid, and dipyridamole (may enhance S-1or capecitabine activity).
b.Nitroimidazoles, including metronidazole and misonidazole (may enhance S-1 activity)
c.Clozapine (may increase risk and severity of hematologic toxicity)
d.Allopurinol (may diminish S-1 activity).
e.Phenytoin (S-1 may enhance phenytoin activity).
f.Flucytosine, a fluorinated pyrimidine antifungal agent (may enhance S-1 activity).
4.Is a pregnant or lactating female.
5.Female patients of childbearing potential must have negative pregnancy test before initiation of study drug dosing. Postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Male and female patients of reproductive potential must agree to employ an effective barrier method of birth control throughout the study and for up to 3 months following discontinuation of study drug.
6.The cardiac arterial flow tests cannot be done
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The frequency of subclinical coronary artery dysfunction, as assessed with the CFR, as compared with the baseline CFR |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
•The CFR between the chemotherapy groups.
•The coronary flow response to the CPT as compared to the baseline values and between the chemotherapy groups.
•The presence of left ventricle regional wall motion abnormalities or global systolic dysfunction
•Cardiac arrhythmias in Holter registration between the 2 groups and as compared to the baseline.
•Plasma sensitive troponin concentration between the 2 groups and as compared to the baseline.
•Frequency and severity of cardiac symptoms and chest pain during treatment.
•Adverse events (Common Terminology Criteria for Adverse Events [CTCAE] version 4.0) between the 2 treatment groups.
•Response rate of cancer to chemotherapy between the 2 treatment groups (RECIST v. 1.1).
•Patient preference of chemotherapy (assessed at the completion of chemotherapy when ≥ 3 cycles were given)
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | Yes |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
| capecitabine, oxaliplatin |
|
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 7 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
Print
