| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| 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 |
| To compare the Overall Survival (OS) of S-1/cisplatin therapy (experimental arm) to 5-FU/cisplatin therapy (control arm) in patients with advanced gastric cancer. |
|
| E.2.2 | Secondary objectives of the trial |
To compare the Overall Response Rate of S-1/cisplatin therapy to 5-FU/cisplatin therapy;
To compare other parameters of antitumor activity of S-1/cisplatin therapy to 5-FU/cisplatin therapy;
To assess the qualitative and quantitative toxicity and reversibility of toxicity of each treatment regimen;
To evaluate the Patient Reported Outcomes, clinical benefit, and time to treatment failure of each treatment arm;
To investigate the relationship between S-1 and 5-FU plasma levels and safety and
efficacy parameters (optional);
Please refer to the protocol for optional objectives, for centers that are able and willing to participate. |
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
1) Exploratory investigation of genetic polymorphisms, Final S1301PRO Amendment2_08June2006, related objectives: exploratory.
2) Exploratory investigation of tumor gene expression levels, Final S1301 PRO Amendment 2_08June2006, related objectives: exploratory. |
|
| 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, unresectable, locally advanced (Stage IV) or metastatic gastric cancer, including adenocarcinoma of the gastro-esophageal junction (See Appendix I for clarification).
3. Has measurable or evaluable but non-measurable disease, defined as follows:
(a) Measurable Disease – Patients with measurable disease as defined by RECIST criteria, ie, the presence of at least one measurable lesion. A measurable lesion is one that can be accurately measured in at least one dimension with the longest diameter ≥ 20 mm using conventional techniques or ≥ 10 mm using spiral Computed Tomography (CT) scan. Locally recurrent disease (other than primary) is accepted if there is at least one measurable lesion (ie, peritoneal mass, lymph node, etc) (See Appendix I for clarification).
(b). Evaluable but Non-measurable Disease – Patients with all lesions below the limits defined above for measurable disease (ie, longest diameter < 20 mm with conventional techniques or < 10 mm with spiral CT) excluding those patients with only a primary lesion and/or with only non-evaluable cancer such as bone metastases, ascites, pleural or pericardial effusions, lymphangitic carcinomatosis of the skin or lung, previously irradiated lesions not in progression, or peritoneal carcinomatosis < 10 mm in diameter with conventional imaging techniques (See Appendix I for clarification).
4. No prior palliative chemotherapy is permitted (See Appendix I for clarification). Adjuvant and/or neo-adjuvant chemotherapy is permitted if more than 12 months has elapsed between the end of adjuvant or neo-adjuvant therapy and first recurrence. This does not qualify as 1st line therapy.
5. Is able to take medications orally.
6. Is ≥ 18 years of age.
7. Is at least 3 weeks from prior major surgery (See Appendix I for clarification).
8. Is at least 4 weeks from prior radiotherapy (See Appendix I for clarification).
9. Has a ECOG performance status 0 to 1 (see Appendix A of the Protocol).
10. Has adequate organ function as defined by the following criteria:
(a) AST (SGOT) and ALT (SGPT) ≤ 2.5 x ULN; if liver function abnormalities are due to
underlying liver metastasis, AST (SGOT) and ALT (SGPT) ≤ 5 x ULN.
(b) Total serum bilirubin of ≤ 1.5 x ULN.
(c) Absolute granulocyte count of ≥ 1,500/mm 3 (ie, ≥ 1.5 x 10 9/L by International Units [IU]).
(d) Platelet count ≥ 100,000/mm 3 (IU: ≥ 100 x 10 9/L).
(e) Hemoglobin value of ≥ 9.0 g/dL. based on measurements obtained prior to any transfusions during the screening period.
(f) Calculated creatinine clearance ≥ 60 mL/min (Cockcroft-Gault formula, see Appendix E of the Protocol, or based on 24-hour urine collection).
11. Is willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures. |
|
| E.4 | Principal exclusion criteria |
A patient will be excluded from this study if he/she does not fulfill the inclusion criteria, or if any of the following conditions are observed:
1. Has had treatment with any of the following within the specified time frame prior to study drug administration:
(a) Any prior palliative chemotherapy or any previous therapy for malignancy, including any chemotherapy, immunotherapy, biologic or hormonal therapy, within the past 5 years (See Appendix I for clarification).
(b) Adjuvant or neo-adjuvant therapy within the past 12 months.
(c) Concurrent treatment with an investigational anti-cancer agent.
(d) Prior cisplatin as neo-adjuvant and/or adjuvant chemotherapy with cumulative dose > 300 mg/m 2.
(e) > 25% of marrow-bearing bone radiated.
(f) Concurrent treatment with an investigational agent or within 30 days from randomization.
(g) Current enrollment in another clinical study (See Appendix I for clarification).
2. Has a serious illness or medical condition(s) including, but not limited to, the following:
(a) Known brain or leptomeningeal metastases.
(b) Uncontrolled ascites requiring drainage at least twice a week.
(c) Other malignancies within the past 5 years, except adequately treated carcinoma-in-situ of the cervix or non-melanoma skin cancer.
(d) Myocardial infarction within the last 6 months, severe/unstable angina, congestive heart failure New York Heart Association (NYHA) class III or IV (see Appendix F of the Protocol).
(e) Chronic nausea, vomiting, or diarrhea.
(f) Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness.
(g) Psychiatric disorder that may interfere with consent and/or protocol compliance.
(h) Known neuropathy, Grade 2 or higher.
(i) 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 drugs interacting with S-1. The following drugs are prohibited because there may be an interaction with S-1:
(a) Sorivudine, uracil, cimetidine, folinic acid, and dipyridamole (may enhance S-1 activity).
(b) Allopurinol (may diminish S-1 activity).
(c) Phenytoin (S-1 may enhance phenytoin activity).
(d) Flucytosine, a fluorinated pyrimidine antifungal agent (may enhance S-1 activity).
4. Is receiving concomitant treatment with drugs interacting with 5-FU. The following drugs are prohibited because there may be an interaction with 5-FU:
(a) Sorivudine, uracil, cimetidine, folinic acid, and dipyridamole (may enhance 5-FU activity).
(b) Allopurinol (may diminish 5-FU activity).
(c) Phenytoin (5-FU may enhance phenytoin activity).
5. Is receiving concomitant treatment with drugs interacting with cisplatin. The following drugs are prohibited because there may be an interaction with cisplatin:
(a) Phenytoin (cisplatin may diminish phenytoin activity).
(b) Aminoglycosides (should be avoided within 8 days after cisplatin administration).
(c) Ethyol® (may diminish cisplatin activity).
6. Is a pregnant or lactating female.
7. Has known hypersensitivity to 5-FU or cisplatin.
8. Patients with reproductive potential who refuse to use an adequate means of contraception (including male patients). |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | Information not present in EudraCT |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Information not present in EudraCT |
| E.6.8 | Bioequivalence | Information not present in EudraCT |
| E.6.9 | Dose response | Information not present in EudraCT |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
| E.6.13 | Others | Information not present in EudraCT |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
| E.7.1.1 | First administration to humans | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Information not present in EudraCT |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
| 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.8.3 |
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.8.5 | The trial involves multiple Member States | Yes |
| 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 | Information not present in EudraCT |
| 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 |
|
| 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 | 6 |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 7 |
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