E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10017758 |
E.1.2 | Term | Gastric cancer |
|
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 overall survival between RAD001+best supportive care (BSC) and placebo+BSC in patients with advanced gastric cancer after progression on prior systemic chemotherapy. |
|
E.2.2 | Secondary objectives of the trial |
• To compare progression free survival between RAD001+BSC and placebo+BSC. • To compare quality of life between RAD001+BSC and placebo+BSC. • To compare time to deterioration of ECOG Performance Status between RAD001+BSC and placebo+BSC • In the RAD001+BSC arm, to evaluate the overall response rate. • To further characterize the safety and tolerability of RAD001 in this population. • To compare Cmin and Cmax (maximum of C1h and C2h) between patients with and without gastrectomy • To compare exposure levels (Cmin and Cmax) of Asia versus Rest of World gastric cancer patients
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Male or female patients ≥ 18 years old • Histologically or cytologically confirmed and documented gastric adenocarcinoma. Patients with advanced gastro-esophageal junction adenocarcinoma, of which the majority, as assessed by the investigator, involves the stomach, will be eligible for inclusion in the study. • Documented progression after 1 or 2 prior systemic chemotherapy lines for advanced disease Note: One line of therapy in the advanced disease setting consists of one or more drugs which are given for 21 days or longer Note: Prior adjuvant/neoadjuvant therapy is allowed. If recurrence occurred during adjuvant/neoadjuvant therapy or ≤ 24 weeks after adjuvant/neoadjuvant therapy completion, the adjuvant/neoadjuvant therapy will be considered as one prior line of systemic chemotherapy for advanced disease Note: Prior treatment with chemotherapy combined with targeted agents is permitted • ECOG performance status of ≤ 2 • Patients with the following laboratory parameters can be included: o Absolute neutrophil count ≥ 1.5 x 109/L (≥ 1500/mm3) o Platelets ≥ 100 x 109/L (≥ 100,000/mm3) o Hemoglobin (Hgb) ≥ 8 g/dL (≥ 4.9 mmol/L) o INR ≤ 2.0 o Serum creatinine ≤ 2 x Upper Limit of Normal (ULN) o Adequate liver function as defined as: • If there is no evidence of liver metastasis: ALT and AST ≤ 2.5 x ULN • If liver metastases are documented: ALT and AST ≤ 5.0 x ULN o Serum bilirubin ≤ 1.5 x ULN o Total serum calcium (corrected for serum albumin) or ionized calcium ≥ Lower Limit of Normal (LLN) o Serum potassium ≥ LLN Note: Calcium, potassium, magnesium and phosphate supplements may be given to correct values that are below the LLN, but must be documented as corrected prior to patients enrolling on the study • Women of childbearing potential must have a negative serum pregnancy test within 7 days of the first administration of study treatments and must be willing to use adequate methods of contraception during the study and for 8 weeks after last study drug administration • Written informed consent
|
|
E.4 | Principal exclusion criteria |
• Patients who have received > 2 prior lines of systemic therapy for advanced disease. See notes under inclusion criterion 3. • Administration of anti-cancer therapy within 3 weeks prior to randomization, except for fluoropyrimidine monotherapy, where randomization may occur 2 weeks after last dose. • Known hypersensitivity to RAD001 (everolimus) or to its excipients, or to other rapamycins (e.g., sirolimus, temsirolimus) • Chronic treatment with steroids (except for oral, topical or local injection) or another immunosuppressive agent • Major surgery ≤ 2 weeks prior to randomization Note: Patients must have recovered from the acute effects of surgery prior to randomization. • Malignant ascites requiring invasive treatment (such as ascites drainage) • Lack of resolution of all acute toxic effects of prior chemotherapy, prior radiotherapy, or surgical procedure according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade ≤ 1, with the exception of neuropathy (inclusion of patients with neuropathy of Grade 2 or less is permitted) and alopecia • Patients with central nervous system metastases • Known history of HIV seropositivity (HIV testing is not mandatory) • Active, bleeding diathesis, or on oral anti-vitamin K medication (except low dose warfarin and acetylsalicylic acid, as long as the INR is ≤ 2.0) • Any malignancy within 3 years prior to randomisation, with the exception of adequately treated in-situ carcinoma of the cervix uteri, basal or squamous cell carcinoma • Any severe and/or uncontrolled medical conditions which could cause unacceptable safety risks or compromise compliance with the protocol, such as: o Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction ≤ 24 weeks prior to enrollment, serious uncontrolled cardiac arrhythmia o Uncontrolled diabetes as defined by fasting serum glucose > 1.5 X ULN o ≥ Grade 3 hypercholesterolemia/hypertriglyceridemia or ≥ Grade 2 hypercholesterolemia/hypertriglyceridemia with history of coronary artery disease (despite lipid-lowering treatment if given) o Acute and chronic, active infectious disorders and nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the complications of this study therapy o Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of study drugs, with the exception of prior gastrectomy (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome). Note: Data from the phase II Japanese study of RAD001 in AGC does not suggest that gastrectomy impairs the absorption of RAD001. o Active skin, mucosa, ocular or GI disorders of Grade > 1 o Chronic obstructive or chronic restrictive pulmonary disease including dyspnea at rest from any cause • Patients who are enterally fed (e.g. via a nasogastric or nasojejunal tube, or via a gastrostomy or jejunostomy) |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Overall survival (OS) defined as the time from randomization to date of death due to any cause. If a patient is not known to have died, survival will be censored at the date of last contact. |
|
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 | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
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) | 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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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) | No |
E.8.2.2 | Placebo | Yes |
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.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |