AIO-STO-0111: A Randomized, Double Blind Study Evaluating Paclitaxel With and Without RAD001 in Patients With Gastric Carcinoma After Prior Chemotherapy

Sponsor

Krankenhaus Nordwest (Other)

Overall Status

Completed

CT.gov ID

NCT01248403

Collaborator

(none)

300

Enrollment

Location

Arms

Actual Duration (Months)

3.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 overall survival compared to patients who are treated with paclitaxel alone.

Condition or Disease	Intervention/Treatment	Phase
Advanced Gastric Cancer Esophagogastric Junction Cancer	Drug: Paclitaxel Drug: RAD001	Phase 3

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 as second-, third- or fourth-line treatment in terms of hazard ratio of overall 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 treatment line (2nd versus 3rd/4th line).

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

300 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, 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

Actual Study Start Date :

Oct 1, 2011

Actual Primary Completion Date :

Jul 1, 2017

Actual Study Completion Date :

Oct 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
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: Everolimus Certican

Arm

Intervention/Treatment

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:

Everolimus

Certican

Outcome Measures

Primary Outcome Measures

overall survival [6 months follow-up]

Secondary Outcome Measures

best overall response [staging every 8 weeks]
progression-free survival [staging every 8 weeks]
number of participants with adverse events as a measure of safety and tolerability [every week until end of treatment]
disease control rate [every 8 weeks]
responders + stable disease ≥12 weeks

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

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