| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
Metastatic Diffuse Gastric Cancer
|
|
| E.1.1.1 | Medical condition in easily understood language |
|
| 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 | Yes |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
To compare the following endpoints for the S-1/cisplatin regimen (experimental arm) with the 5-FU/cisplatin regimen control arm) in patients with metastatic diffuse gastric cancer:
- overall survival (OS) |
|
| E.2.2 | Secondary objectives of the trial |
To compare the following endpoints for the S-1/cisplatin regimen (experimental arm) with the 5-FU/cisplatin regimen (control arm) in patients with metastatic diffuse gastric cancer:
- Progression-free survival (PFS)
- Time to treatment failure (TTF)
- Safety and tolerability
- Antitumor activity: Overall Response Rate (ORR), duration of response (DR), time to tumor response (TTR)
- Clinical benefit: Change in performance status (PS), body weight, and anorexia
- Healthcare Utilization |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
A patient must meet all of the following inclusion criteria to be eligible for enrollment in this study:
1. Has given written informed consent.
2. Has histologically confirmed by Central Pathology Review, unresectable (at the time of screening
for study eligibility), metastatic diffuse gastric cancer including carcinoma of the gastroesophageal
junction as defined in Appendix F (Pathology Central Review: Histologic Criteria).
Patients must only be randomized after central pathology review has confirmed diffuse histologic type. Gastro-esophageal junction involvement must be documented by endoscopic, radiologic, surgical or pathology report.
3. Has had no prior chemotherapy for gastric cancer; however, adjuvant and/or neo-adjuvant
chemotherapy is permitted if more than 12 months have elapsed between the end of adjuvant or
neo-adjuvant therapy and first recurrence.
4. Has a life expectancy of at least 3 months.
5. Is able to take medications orally and without being crushed or removed from the capsule and given through any form of feeding tube.
6. Is ≥18 years of age.
7. First dose of study medication will be at least 3 weeks from prior major surgery.
8. First dose of study medication will be at least 4 weeks from prior radiotherapy.
9. Has an ECOG performance status 0 to 1 (see Appendix A).
10. Has adequate organ function as defined by the following criteria:
a. Aspartate aminotransferase (AST; SGOT) and alanine aminotransferase (ALT; SGPT) ≤2.5 ×
upper limit of normal (ULN); if liver function abnormalities are due to underlying liver
metastasis, AST (SGOT) and ALT (SGPT) ≤5 × ULN.
b. Total serum bilirubin of ≤1.5 × ULN.
c. Absolute neutrophil count of ≥1,500/mm3 (ie, ≥1.5 × 109/L by International Units [IU]).
d. Platelet count ≥100,000/mm3 (IU: ≥100 × 109/L).
e. Hemoglobin value of ≥9.0 g/dL based on measurements obtained prior to any transfusions during the Baseline period.
f. Creatinine clearance (CrCl) ≥60 mL/min.
11. Is willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
12. Women of childbearing potential must have a negative pregnancy test (urine or serum) prior to
randomization. Females and males must agree to adequate birth control if conception is possible during the study; and males and females must agree to adequate birth control for up to 6 months
after the discontinuation of study medication. |
|
| E.4 | Principal exclusion criteria |
Exclude a patient from this study if any of the following conditions are observed:
1. Has only the following type(s) of non-measurable lesion(s):
a. Ascites, pleural or pericardial effusions.
b. Previously irradiated lesions not in progression.
2. Has had treatment with any of the following within the specified time frame prior to study medication administration:
a. Any prior chemotherapy or any previous therapy for malignancy other than gastric cancer,
including any chemotherapy, immunotherapy, biologic or hormonal therapy, within the past
5 years.
b. Adjuvant or neo-adjuvant therapy within the past 12 months.
c. Treatment with any investigational agent within 30 days of randomization.
d. Prior cisplatin as neo-adjuvant and/or adjuvant chemotherapy with cumulative dose
>360 mg/m2.
e. >25% of marrow-bearing bone radiated.
3. Has a serious illness or medical condition(s) including, but not limited to, the following:
a. Known acute systemic infection.
b. Known brain or leptomeningeal metastases.
c. Ascites ≥Grade 3 (ie, invasive intervention is indicated).
d. Other malignancies within the past 5 years, except adequately treated carcinoma-in-situ of the
cervix or non-melanoma skin cancer.
e. Myocardial infarction within the last 6 months, severe/unstable angina, congestive heart failure New York Heart Association (NYHA) class III or IV (see Appendix E);
f. Chronic nausea, vomiting, or diarrhea.
g. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness.
h. Any disorder that may interfere with consent and/or protocol compliance.
i. Peripheral neuropathy, Grade 2 or higher.
j. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study medication 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.
4. Has lost ≥10% of their body weight in the preceding 3 months at time of signed ICF.
5. Is receiving treatment with drugs interacting with S-1, 5-FU, or cisplatin (see the required washout
period before starting a patient on treatment [Section 6.6]). The following drugs are
prohibited:
a. Sorivudine, brivudine, uracil, eniluracil, cimetidine, folinic acid, ipyridamole, flucytosine, methotrexate, and nitroimidazoles, including metronidazole and misonidazole (may enhance S-1 and 5-FU activity).
b. Clozapine (may increase risk and severity of hematologic toxicity with S-1).
c. Allopurinol (may diminish 5-FU activity).
d. Ethyol (may diminish cisplatin activity [see package insert]).
6. Is a pregnant or lactating female.
7. Has known hypersensitivity to 5-FU or cisplatin.
Additional Criteria for Randomization
Immediately prior to randomization, the following criteria must be met:
1. Has not experienced ≥5% loss of their body weight between signed ICF and randomization;
2. Has an ECOG performance status of 0 or 1 on Cycle 1, Day 1;
3. Has no sign of infection on Cycle 1 Day 1. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Overall Survival (OS)-
Survival is the primary endpoint of this study and is defined as the time from date of randomization to date of death. In the absence of death confirmation or for patients alive at the time of analysis, survival time will be censored at the date of last study follow-up, or the cut-off date, whichever is earlier. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| After 427 events (deaths) assuming a sample size of 500 patients and a median survival time of approximately 7 months in the control arm. |
|
| E.5.2 | Secondary end point(s) |
Progression-Free survival (PFS),
Time to Treatment Failure (TTF),
Safety and Tolerability
Overall response rate (ORR),
Duration of Response (DR),
Time to Tumor Response (TTR),
Clinical Benefit and Healthcare Utilization |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| After 427 events (deaths) assuming a sample size of 500 patients and a median survival time of approximately 7 months in the control arm. |
|
| 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) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| 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 | Yes |
| E.8.1.6 | Cross over | No |
| 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 | No |
| 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
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 56 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Argentina |
| Belgium |
| Brazil |
| Bulgaria |
| Colombia |
| Croatia |
| Estonia |
| Germany |
| Hungary |
| Italy |
| Mexico |
| Poland |
| Portugal |
| Romania |
| Russian Federation |
| South Africa |
| Spain |
| Ukraine |
| United Kingdom |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| 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 | 4 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 6 |
| E.8.9.2 | In all countries concerned by the trial months | 7 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
Print
