To compare overall survival between RAD001+BSC and placebo+BSC in patients with advanced gastric cancer after progression on prior systemic chemotherapy.
ID
Source
Brief title
Condition
- Gastrointestinal neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint of this study is overall survival (OS), defined as the
time from date of randomization to date of death due to any cause. If death has
not been observed at the date of the analysis cutoff then OS will be censored
at the date of the last contact.
Secondary outcome
The secondary efficacy objectives were to compare RAD001 against placebo with
respect to progression-free survival (PFS), quality of life, and time to
definitive deterioration in the ECOG PS scale.
A hierarchical testing strategy will be adopted in this study. PFS will be
compared between the two treatment arms provided the primary endpoint
Background summary
Currently, there is no established standard of care for the treatment of
gastric carcinoma. Surgery, which is the only curative option, is effective
only when performed on patients in the earliest stages of the disease. The
majority of patients present with more advanced disease (inoperable or
metastatic gastric cancer) and do not qualify for surgery. First-line therapy
varies but typically consists of regimens combining 5-FU and its derivatives
with taxanes, platinum-based drugs, or irinotecan. Irrespective of the
treatment received, survival is limited (with 5-year survival of around 20%)
and a need for second and third line treatment is needed.
There is a medical need for better therapy for advanced gastric. RAD001 has a
potential to act directly on the tumor cells by inhibiting tumor cell growth
anad proliferation. On the other hand RAD001 has also a potential to act
indirectly by inhibiting angiogenesis leading to reduced tumor vascularity.
Phase II data show a 54.7% disease control rate in Japanese patients receiving
everolimus monotherapy for advanced gastric cancer after one or two prior
chemotherapy regimens
Study objective
To compare overall survival between RAD001+BSC and placebo+BSC in patients with
advanced gastric cancer after progression on prior systemic chemotherapy.
Study design
This is a phase III, double blind, randomized, international study comparing
treatment of RAD001 plus best supportive care (BSC) against treatment with
matching placebo plus BSC in patients with advanced gastric cancer who have
progressed after one or two prior chemotherapy regimens for advanced disease.
Patients will be randomized to receive either RAD001 or placebo; randomization
will be unbalanced, 2:1 in favor of RAD001. Given the regional differences in
management of Advanced Gastric Carcinoma (AGC) and the known association
between performance status and outcomes in AGC, patients will be stratified by
number of prior chemotherapy regimens for advanced disease and region (Asia
versus Rest of World).
Study treatment will be continued until progression or intolerable toxicity.
After progression, patients will continue to be followed for survival every
three months till death or until study completion. If at either the interim or
the final analysis, the superiority of RAD001 is demonstrated, the trial will
be stopped and all available data will be reviewed by the Study Steering
Committee. A decision may be made to offer RAD001 to patients on placebo at
that time.
Intervention
RAD001 plus best supportive care versus placebo plus best supportive care
Best supportive care will be provided to all patients in accordance with the
local practices of a
given institution or center. Best supportive care cannot contain any
anti-cancer treatments.
Study burden and risks
Toxicity of RAD001 (everolimus). Radiation exposure of CT-scans.
Obtaining blood samples may cause some discomfort, bruising, bleeding from the
site of sampling, formation of a blood clot, and, in rare cases, infection.
Raapopseweg 1
6824 DP Arnhem
NL
Raapopseweg 1
6824 DP Arnhem
NL
Listed location countries
Age
Inclusion criteria
- Histologically or cytologically confirmed and documented gastric adenocarcinoma.
- Progression after 1 or 2 prior systemic chemotherapy treatments for advanced disease. Prior adjuvant/neoadjuvant therapy is allowed.
- ECOG performance status of * 2
- Patients with the following laboratory parameters:
* Absolute neutrophil count * 1.5 x 109/L
* Platelets * 100 x 109/L
* Hemoglobin (Hgb) * 4.9 mmol/L
* INR * 2.0
* Serum creatinine * 2 x Upper Limit of Normal (ULN)
* Adequate liver function (no evidence of liver metastasis: ALT and AST * 2.5 x ULN and with liver metastases: ALT and AST * 5.0 x ULN)
* Serum bilirubin * 1.5 ULN (Upper Limit of Normal)
* Normal serum calcium and serum potassium
Exclusion criteria
- Patients who have received > 2 prior systemic therapies for advanced disease. Note: If recurrence occurred during or * 24 weeks after adjuvant/neoadjuvant therapy the adjuvant/neoadjuvant therapy will be considered as one prior regimen of systemic chemotherapy.
- Administration of anti-cancer therapy within 3 weeks prior to randomization
- Known hypersensitivity to RAD001 (everolimus) or to other rapamycins
- Chronic treatment with steroids
- Major surgery * 2 weeks prior to randomization
- Malignant ascites requiring invasive therapy
- Lack of resolution of all acute toxic effects (excluding alopecia) of prior chemotherapy, radiotherapy, or surgical procedure CTC grade * 1 except neuropathy with grade 2 or less and alopecia.
- Central nervous system metastases
- Active, bleeding diathesis, or on oral anti-vitamin K medication (except low dose warfarin and acetylsalicylic acid (as long asINR is * 2.0)
- Any malignancy within 3 years of randomization (except in situ carcinoma of cervix, basal or squamous cell carcinoma)
- Any severe and/or uncontrolled medical conditions such as:
* Unstable cardiac disease
* Uncontrolled diabetes
* Acute and chronic, uncontrolled active infectious disorders and nonmalignant medical illnesses
* 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 show that gastrectomy impairs the absorption of RAD001.
* Active skin, mucosa, ocular or GI disorders of Grade > 1
* Chronic obstructive or restrictive pulmonary disease including dyspnea at rest from any cause
- Patients who are enterally fed
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2008-00654420-NL |
| CCMO | NL27725.018.09 |