A Phase III, Multi-center, Randomized, Controlled Study to Compare the Efficacy and Safety of Gemcitabine Alone vs. ON 01910.Na Combined With Gemcitabine in Patients With Previously Untreated Metastatic Pancreatic Cancer
This will be a Phase III study with sample size recalculation after 100 events have
occurred. The study will be open-label, randomized, controlled, multi-center and will be
conducted at approximately 200 to 300 study sites (60 to 80 study sites in the first portion
of the trial).
In the first portion of the study, a total of 150 patients with metastatic pancreatic cancer
who have received no prior chemotherapy for this disease will be randomized in a 2:1 fashion
to 1 of the 2 following treatment regimens:
- Arm A: Gemcitabine 1000 mg/m2 weekly for 3 weeks of a 4 week cycle + ON 01910.Na 1800
mg/m2 via 2 hr continuous intravenous infusion (CIV) infusions administered twice
weekly for 3 weeks of a 4 week cycle (approximately 100 patients)
- Arm B: Gemcitabine only, 1000 mg/m2 weekly for 3 weeks of a 4 week cycle
(approximately 50 patients).
Patients will be stratified at entry using the Eastern Cooperative Oncology Group (ECOG)
performance status (ECOG scores of 0 1 vs. ECOG scores of 2; patients with higher scores
will not be enrolled).
Patients will remain on study until disease progression or death from any cause, whichever
comes first. Moreover, after treatment discontinuation for any cause, all patients will be
followed until death.
After 150 patients have been enrolled, accrual will pause and patients will be followed
until 100 deaths have occurred. At that time, the Data Safety Monitoring Committee (DSMC)
will oversee a formal interim analysis to compare overall survival (OS) between the 2 groups
and may recommend early stopping for futility. If the study continues after interim
analysis, then the randomization scheme will continue up to 364 patients or the
newly-calculated sample size. The maximum number of enrolled patients will be 650. The
number of clinical sites may be expanded up to approximately 200 to 300 centers.
Patients in the gemcitabine-only arm (Arm B) will not be allowed to cross over to the
combined treatment arm (Arm A). In addition, no palliative radiotherapy will be allowed
during the trial.
The primary analysis will compare OS in the ON 01910.Na + gemcitabine arm (Arm A) vs.
gemcitabine-only arm (Arm B) once an appropriate number of events has been reached. There
are 2 secondary efficacy outcomes: progression-free survival (PFS) and objective response.
Toxicity will be graded according to the National Cancer Institute Common Terminology
Criteria for Adverse Events v4.03. Grade 3 and 4 hematologic toxicities and > Grade 2
non-hematologic toxicities will be monitored.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
This study's primary outcome is overall survival, defined as the time from randomization to death from any cause. All patients will be followed until death. Patients lost to follow-up will be censored at the time last known alive.
Wells Messersmith, MD
Anschutz Cancer Pavilion
United States: Food and Drug Administration
|Roswell Park Cancer Institute||Buffalo, New York 14263|
|University of Colorado Cancer Center||Denver, Colorado 80262|
|Fox Chase Cancer Center||Philadelphia, Pennsylvania 19111|
|Vanderbilt-Ingram Cancer Center||Nashville, Tennessee 37232-6838|
|University of Rochester Medical Center||Rochester, New York 14642|
|Yale Cancer Center||New Haven, Connecticut 06520-8028|
|Mount Sinai Comprehensive Cancer Center||Miami Beach, Florida 33140|
|Seattle Cancer Care Alliance||Seattle, Washington 98109|
|McLeod Regional Medical Center||Florence, South Carolina 29501|
|Billings Clinic Cancer Center||Billings, Montana 59107-5100|
|Medical University of South Carolina - Hollings Cancer Center||Charleston, South Carolina 29425|
|UCSD Moores Cancer Center||La Jolla, California 93093|
|Karmanos Cancer Institute||Detroit, Michigan 48201|
|Premiere Oncology||Santa Monica, California 90404|
|University of Kansas Cancer Center||Kansas City, Kansas 66160|
|New York University Langone Medical Center||New York, New York 10016|
|University of North Carolina Lineberger Comprehensive Cancer Center||Chapel Hill, North Carolina 27599|
|University of Hawaii Cancer Center||Honolulu, Hawaii 96813|
|UMass Medical School||Worcester, Massachusetts 01655|
|Kaiser Permanente NW||Portland, Oregon|
|Levine Cancer Institute||Charlotte, North Carolina 28211|
|Desert Comprehensive Cancer Center||Palm Springs, California 92262|
|Cone Health Cancer Center||Greensboro, North Carolina|
|Kaiser Permanente Colorado||Denver, Colorado 80205|
|Hendersonville Hematology and Oncology at Pardee||Hendersonville, North Carolina 28971|
|Rex Cancer Center UNC Healthcare||Raleigh, North Carolina 27607|
|St. Alexis Medical Center-Mid Dakota Clinic PC||Bismarck, North Dakota 58501|
|University of Cincinnati Cancer Center||Cincinnati, Ohio 45219|
|Pacific Cancer Care||Salinas, California 93901|
|Poudre Valley Cancer Center of the Rockies||Fort Collins, Colorado 80528|