E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with advanced gastric cancer who have progressed after one line of chemotherapy |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
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 |
Primary objective: to assess the treatment effect on progression-free survival (PFS) in patients who receive AUY922 on a once-weekly schedule versus patients who receive docetaxel or irinotecan.
|
|
E.2.2 | Secondary objectives of the trial |
Key secondary objective: to estimate the overall survival treatment effect and other time-related endpoints. Additional secondary objectives: - to estimate the objective response rate (ORR), to evaluate safety (based on CTCAE Version 3.0) and tolerability, and to characterize the pharmacokinetics (PK) of AUY922 patients in both Asian and Caucasian populations where feasible. Biomarker objectives include the investigation of the pharmacodynamic effect of AUY922 on HSP90 client proteins in pre- and post-therapy tumor tissue (where biopsies are available) and blood, pre- vs. post-treatment and to investigate cellular anti-tumor activity of AUY922 by measuring apoptosis and/or proliferation indices in tumor tissue (where biopsies are available) and blood, pre- vs. post-treatment.
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Patients with cytological or histological confirmed gastric adenocarcinoma or gastroesophageal junction adenocarcinoma 2) Patients with progressive disease (radiological confirmation required) after one line of chemotherapy for advanced gastric cancer. In addition, patients may have also received prior adjuvant if recurrence occurred ≥6 months after adjuvant therapy completion 3) Patients must have at least one measurable lesion as defined by RECIST. Irradiated lesions are only evaluable for disease progression 4) Patients who meet the following criteria will be eligible for PET assessments: - At least one lesion must be measurable ( >2cm) - To be eligible for follow-up scans, patients should have uptake of the tracer in at least one lesion where the tumor-muscle ratio is >2 - Able to lie still and flat on the PET table 5) Age ≥ 18 years or age of consent in country of residence 6) Able to sign Informed Consent 7) World Health Organization (WHO) Performance Status of ≤ 1 8) Life expectancy of ≥ 12 weeks Patients must have the following laboratory values: 9) Hematologic: - Absolute Neutrophil Count (ANC) ≥1.5x109/L - Hemoglobin (Hgb) ≥ 9 g/dl - Platelets (plt) ≥100x109/L 10) Biochemistry: - Potassium within normal limits - Total calcium (corrected for serum albumin) and Phosphorus within normal limits - Magnesium above LLN or correctable with supplements - Adequate liver function defined as: AST/SGOT and ALT/SGPT ≤ 1.5 x Upper Limit of Normal (ULN) if AP > 2.5 ULN AST/SGOT and ALT/SGPT ≤ 2.5 x Upper Limit of Normal (ULN) if AP ≤ 5.0 x ULN if liver metastases are present Serum bilirubin ≤ 1.5 x ULN Serum creatinine ≤ 1.5 x ULN or 24-hour clearance ≥ 50 ml/min 11) Negative serum pregnancy test. The serum pregnancy test must be obtained prior to the first administration of study medication (≤ 72 hours prior to dosing) in all pre-menopausal women and women <2 years after the onset of menopause
|
|
E.4 | Principal exclusion criteria |
1) Patients with CNS metastasis which are: • Symptomatic or • Require treatment for symptom control and/or • Growing Note: Patients without clinical signs or symptoms of CNS involvement are not required to have a CT/MRI of the brain 2) Prior treatment with any HSP90 or HDAC inhibitor compounds 3) Patients who received systemic anti-cancer treatment prior to the first dose of study medication within the following time frames: • Radiotherapy, conventional chemotherapy: within 4 weeks • Monoclonal antibodies such as Trastuzumab treatment within 4 weeks • Palliative radiotherapy: within 2 weeks • Nitrosoureas and mitomycin: within 6 weeks • Any continuous dosing (i.e. daily dosing, every-other-day dosing, Monday- Wednesday-Friday dosing, weekly etc) of systemic anti-cancer treatment for which the recovery period is not known, or investigational drugs (i.e. targeted agents) within a duration of ≤ 5 half lives of the agent and their active metabolites (if any) 5) Treatment with therapeutic doses of coumarin-type anticoagulants. (Maximum daily dose of 2 mg, for line patency permitted) 6) Known sensitivity to taxanes, drugs formulated with polysorbate 80, or patients with Acute Myeloid Leukemia 7) Concomitant use of agents that induce, inhibit or are metabolized by CYP3A4, neuromuscular blocking agents and Atazanavir sulfate 8) Unresolved diarrhea ≥ CTCAE grade 1 9) Patients with malignant ascites that require invasive treatment 10) Patients who do not have either an archival tumor sample available or are unwilling to have a fresh tumor sample collected at baseline 11) Pregnant or lactating women 12) Fertile women of childbearing potential (WCBP) not using double-barrier methods of contraception (abstinence, oral contraceptives, intrauterine device or barrier method of contraception in conjunction with spermicidal jelly, or surgically sterile). Male patients whose partners are WCBP not using double-barrier methods of contraception. 13) Patients with acute or chronic liver or renal disease 14) Other concurrent severe and/or uncontrolled medical conditions that could cause unacceptable safety risks or compromise compliance with the protocol. 15) Major surgery ≤ 2 weeks prior to randomization or who have not recovered from such therapy 16) Impaired cardiac function , including any one of the following: • History (or family history) of long QT syndrome • Mean QTc ≥ 450 msec on baseline ECG • History of clinically manifested ischemic heart disease ≤ 6 months prior to study start • History of heart failure or left ventricular (LV) dysfunction (LVEF ≤ 45%) by MUGA or ECHO • Clinically significant ECG abnormalities • History or presence of atrial fibrillation, atrial flutter or ventricular arrhythmias including ventricular tachycardia or Torsades de Pointes • Other clinically significant heart disease (e.g. congestive heart failure, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen) • Clinically significant resting bradycardia (< 50 beats per minute) • Patients who are currently receiving treatment with any medication which has a relative risk of prolonging the QTcF interval or inducing Torsades de Pointes and cannot be discontinued or switched to an alternative drug prior to commencing start of treatment. • Obligate use of a cardiac pacemaker 17) Known diagnosis of HIV infection (HIV testing is not mandatory) 18) Patients with a history of another primary malignancy that is clinically significant or requires active intervention 19) Patients unwilling or unable to comply with the protocol
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Primary Endpoint Progression-free survival (PFS): Progression-free survival (PFS) is the time from the date of randomization to the date of event defined as the first documented progression or death due to any cause. If a patient has not had an event, PFS is censored at the date of last adequate tumor assessment Secondary Endpoints include - Efficacy: Overall survival (OS), and Objective response rate (ORR) Response assessments per RECIST - Safety: Incidence of adverse drug reactions and serious adverse drug reactions as assessed by CTCAE Version 3.0 - PK: Exposure of AUY922 and parameters: e.g. Cmax, and Ctrough (AUC and T1/2 in PK subpopulation), - Biomarkers: Temporal and magnitude changes in blood and tissue marker levels
|
|
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 | Yes |
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 | 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.8.4.1 | 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 | 20 |
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
|
End of study is defined as the time when a patients is discontinued permanently from any study evaluation (including survival data collection). The End of trialhas occured when the last patient has been followed 2 years for survival after randomization. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 1 |
E.8.9.2 | In all countries concerned by the trial days | 0 |