A Randomized, Double Blind Study Evaluating Paclitaxel With and Without RAD001 in Patients With Gastric Carcinoma After Prior Chemotherapy (AIO-STO-0111)
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Purpose
Adult patients with gastric carcinoma which has progressed after initial treatment with a fluoropyrimidines-containing regimen will be treated with paclitaxel plus RAD001 or plus placebo. The hypothesis is that patients with RAD001 have significantly prolonged progression-free survival compared to patients who are treated with paclitaxel alone.
| Condition | Intervention | Phase |
|---|---|---|
|
Advanced Gastric Cancer Esophagogastric Junction Cancer |
Drug: Paclitaxel Drug: RAD001 |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Treatment |
| Official Title: | A Randomized, Double-blind, Multi-center Phase III Study Evaluating Paclitaxel With and Without RAD001 in Patients With Gastric Carcinoma Who Have Progressed After Therapy With a Fluoropyrimidine-containing Regimen |
- overall survival [ Time Frame: 6 months follow-up ] [ Designated as safety issue: No ]
- best overall response [ Time Frame: staging every 8 weeks ] [ Designated as safety issue: No ]
- progression-free survival [ Time Frame: staging every 8 weeks ] [ Designated as safety issue: No ]
- number of participants with adverse events as a measure of safety and tolerability [ Time Frame: every week until end of treatment ] [ Designated as safety issue: Yes ]
- disease control rate [ Time Frame: every 8 weeks ] [ Designated as safety issue: No ]responders + stable disease ≥12 weeks
| Estimated Enrollment: | 480 |
| Study Start Date: | October 2011 |
| Estimated Study Completion Date: | January 2016 |
| Estimated Primary Completion Date: | January 2016 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Active Comparator: paclitaxel + placebo
Paclitaxel 80 mg/m2 on day 1, day 8 and day 15 of every 28-day cycle. + Placebo (2 tablets / day) d1-d28 |
Drug: Paclitaxel
Paclitaxel 80 mg/m2 on day 1, day 8 and day 15 of every 28-day cycle.
|
|
Experimental: paclitaxel + RAD001
Paclitaxel 80 mg/m2 on day 1, day 8 and day 15 of every 28-day cycle. + RAD001 10mg (2 x5 mg tablets / day) d1-d28 |
Drug: Paclitaxel
Paclitaxel 80 mg/m2 on day 1, day 8 and day 15 of every 28-day cycle.
Drug: RAD001
RAD001 10mg (2 x5 mg tablets / day) d1-d28
Other Names:
|
Detailed Description:
This is a randomized, double-blind, phase III two-arm multi-center study aiming at estimating the relative efficacy of the combination of RAD001 and paclitaxel versus that of paclitaxel alone in terms of hazard ratio of progression-free survival in patients with gastric cancer who have relapsed after one treatment regimen containing a fluoropyrimidine (e.g., 5-FU, S-1, capecitabine and other 5-FU prodrugs or derivatives). Patients will be randomized in a 1:1 ratio for a total of 240 patients per treatment arm. Randomization will be stratified according to performance status (0-1 versus 2), prior taxan use (yes vs. no) and lesions (measurable vs evaluable).
Study treatment will be continued until progression or intolerable toxicity. Patients will be seen at baseline/screening, and weekly for paclitaxel administration and safety assessment until disease progression or discontinuation of trial therapy for other reasons. Radiological tumor assessment will be performed every second cycle (every 8 weeks) or earlier if clinically indicated. Post-study follow-up will be completed every 8 weeks for survival.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Male or female patients ≥ 18 years old
- Histologically or cytologically confirmed and documented gastric adenocarcinoma. Adenocarcinomata of the gastro-esophageal junction will be allowed, if they have advanced disease (inoperable, recurrent or metastatic disease).
- Documented progressive disease during/after one, two or three prior treatments containing 5FU and/or its precursors or derivatives in the palliative setting
- At least one measurable or evaluable lesion by RECIST as determined by Computed Tomography (CT) Scan or Magnetic Resonance Imaging (MRI)
- ECOG performance status of 0, 1 or 2
The following laboratory parameters:
- Absolute neutrophil count ≥ 1.5 x 109/L
- Platelets ≥ 100 x 109/L
- Hemoglobin (Hgb) ≥ 9 g/dL
- Serum creatinine ≤ 2 x Upper Limit of Normal (ULN)
- Adequate liver function:
- Total serum calcium (corrected for serum albumin) or ionized calcium ≥ LLN
- 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 3 months after last study drug administration.
- Written informed consent
Exclusion Criteria:
- Current treatment with any anti cancer therapy or treatment with anti cancer therapy ≤ 2 weeks prior to study treatment start unless rapidly progressing disease is measured
- Known hypersensitivity to RAD001 (everolimus) or to its excipients, or to other rapamycins (e.g. sirolimus, temsirolimus)
- Known prior history of hypersensitivity to paclitaxel.
- Paclitaxel refractory disease, which is defined as a disease progression under or within 12 weeks of last taxan treatment
- Chronic treatment with steroids (except for oral, topical or local injection) or another immunosuppressive agent
- Major surgery ≤ 2 weeks prior to starting study treatment or patients who have not recovered from such therapy
- Lack of resolution of all acute toxic effects (excluding alopecia) of prior chemotherapy, prior radiotherapy, or surgical procedure to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grade <= 1. Note: Neuropathy due to prior chemotherapy is allowed.
Unstable CNS disease
- Requiring increasing doses of steroids to maintain stable neurological status
- Deteriorating / changing neurological status
- Known history of HIV seropositivity (HIV testing is not mandatory) or Hepatitis B or C.
- Active, bleeding diathesis or on oral anti-vitamin K medication (except low dose warfarin, as long as the INR is <= 2.0)
- Any other severe and/or uncontrolled medical conditions
Contacts and Locations| Contact: Salah-Eddin Al-Batran, MD | +496976014420 | albatran@aol.com |
| Contact: Claudia Pauligk, PhD | +496976013906 | pauligk.claudia@khnw.de |
| Germany | |
| Krankenhaus Nordwest | Recruiting |
| Frankfurt/Main, Germany, 60488 | |
| Contact: Salah-Eddin Al-Batran, MD +496976014420 albatran@aol.com | |
| Contact: Claudia Pauligk, PhD +496976013906 pauligk.claudia@khnw.de | |
| Principal Investigator: Salah-Eddin Al-Batran, MD | |
| Principal Investigator: | Salah-Eddin Al-Batran, MD | Krankenhaus Nordwest |
More Information
No publications provided
| Responsible Party: | Krankenhaus Nordwest |
| ClinicalTrials.gov Identifier: | NCT01248403 History of Changes |
| Other Study ID Numbers: | CRAD001RDE35T |
| Study First Received: | November 23, 2010 |
| Last Updated: | April 22, 2013 |
| Health Authority: | Germany: Federal Institute for Drugs and Medical Devices |
Keywords provided by Krankenhaus Nordwest:
|
RAD001 Paclitaxel gastric cancer advanced gastric or esophagogastric junction cancer |
Additional relevant MeSH terms:
|
Carcinoma Stomach Neoplasms Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms Neoplasms by Site Digestive System Diseases Gastrointestinal Diseases Stomach Diseases Everolimus Sirolimus Paclitaxel Immunosuppressive Agents |
Immunologic Factors Physiological Effects of Drugs Pharmacologic Actions Antibiotics, Antineoplastic Antineoplastic Agents Therapeutic Uses Antifungal Agents Anti-Infective Agents Anti-Bacterial Agents Tubulin Modulators Antimitotic Agents Mitosis Modulators Molecular Mechanisms of Pharmacological Action Antineoplastic Agents, Phytogenic |
ClinicalTrials.gov processed this record on May 21, 2013