Trial record 1 of 1 for:    A Phase II/III, Multi-center, Randomized, Controlled Study to Compare the Efficacy and Safety of Gemcitabine Alone vs. ON 01910.Na
Previous Study | Return to List | Next Study

Gemcitabine and ON 01910.Na in Previously Untreated Metastatic Pancreatic Cancer (ONTRAC)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Academic Oncology Gastrointestinal Cancer Consortium (AGICC)
Information provided by (Responsible Party):
Onconova Therapeutics, Inc.
ClinicalTrials.gov Identifier:
NCT01360853
First received: May 24, 2011
Last updated: August 27, 2013
Last verified: August 2013
  Purpose

The question being asked in this study is: Will patients with advanced pancreatic cancer live significantly longer if they are treated with a combination of Gemcitabine and ON 01910.Na than if they are treated with Gemcitabine alone? There are two parts to this study. In the first part of the study, patients with metastatic pancreatic cancer who have received no prior chemotherapy for this disease will be assigned by chance either to the group that will be treated with both Gemcitabine and ON 01910.Na (about 100 patients will be in this group) or, to the group that will be treated with Gemcitabine only (about 50 patients will be in this group). How long patients survive in the 2 groups will be compared. If it looks like there is no difference between the groups, the study will stop. If it looks like patients in the group that were treated with both Gemcitabine and ON 01910.Na survive longer, the study will continue into a second part where more patients will be treated in order to confirm and better understand the findings of the first part of the study.


Condition Intervention Phase
Metastatic Pancreatic Adenocarcinoma
Drug: ON 01910.Na
Drug: Gemcitabine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Onconova Therapeutics, Inc.:

Primary Outcome Measures:
  • Survival [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Progression-free survival [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    Progression-free survival is defined as the time from the randomization to documented disease progression or death. Patients who are alive and do not have disease progression by the clinical cutoff will be censored at the dates of their last tumor evaluation. Kaplan-Meier curves for PFS will be compared using a stratified log-rank test (stratified by ECOG status: 0-1 vs. 2). Hazard ratios and 95% confidence intervals will be estimated using stratified Cox proportional hazards models.

  • Tumor size [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    Objective tumor response rates using Response Evaluation Criteria In Solid Tumors (RECIST).

  • Safety/tolerability [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
    Toxicity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.03

  • QOL questionnaire [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    Quality of life (QOL) questionnaire, using the European Organisation for Research and Treatment of Cancer(EORTC) QLQ-C30 version 3.

  • Biomarkers [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    In this study, archival tissue will be collected and analyzed in order to identify molecular characteristics of pancreas tumors, which may confer susceptibility or resistance to gemcitabine alone or in combination with ON 01910.Na.

  • Population Pharmacokinetics [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    Measurement of ON 01910.Na in plasma of all patients in Arm A 1 hour after starting ON 01910.Na infusion at Day 1 and Day 15 in Cycle 1 only.

  • Full Pharmacokinetics [ Time Frame: 18 Months ] [ Designated as safety issue: No ]
    At a limited number of sites, blood samples for measurement of ON 01910.Na and gemcitabine will be obtained at Cycle 1 Day 1 only, in a subset of 10 patients in Arm A, at the following 12 time-points: predose; 15 min after starting gemcitabine infusion; 30 min, immediately before ending gemcitabine infusion; 15 min after starting ON 01910.Na infusion; 30 min after ON 01910.Na infusion start; immediately before ending ON 01910.Na infusion; and, 15 min, 30 min, 1 hr, 2 hr, 4 hr and 8 hr after ending ON 01910.Na infusion.


Estimated Enrollment: 650
Study Start Date: May 2011
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A: Combination
Arm A: Gemcitabine, 1000 mg/m2 weekly for 3 weeks of a 4 week cycle, + ON 01910.Na, 1800 mg/m2 via 2 hr CIV infusions administered twice weekly for 3 weeks of a 4 week cycle.
Drug: ON 01910.Na
ON 01910.Na, 1800 mg/m2 via 2 hr CIV infusions administered twice weekly for 3 weeks of a 4 week cycle.
Other Name: rigosertib sodium
Drug: Gemcitabine
Gemcitabine 1000 mg/m2 weekly for 3 weeks of a 4 week cycle.
Other Names:
  • Gemzar
  • Gemcitabine HCl
Active Comparator: Arm B: Gemcitabine only
Arm B: Gemcitabine only, 1000 mg/m2 weekly for 3 weeks of a 4 week cycle.
Drug: Gemcitabine
Gemcitabine, 1000 mg/m2 weekly for 3 weeks of a 4 week cycle.
Other Names:
  • Gemzar
  • Gemcitabine HCl

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients at least 18 years old presenting with histopathologically or cytologically confirmed metastatic adenocarcinoma of the pancreas; metastatic disease is defined as disease which has spread beyond the peri-pancreatic lymph nodes.
  • Patients must have received no prior chemotherapy for pancreatic cancer, including adjuvant chemotherapy.
  • Measurable disease, defined as lesions that can be accurately measured in at least 1 dimension with longest diameter (LD) ≥20 mm using conventional techniques or ≥10 mm with spiral computed tomography (CT) scan; measurable lymph nodes must be ≥15 mm in the short axis.
  • ECOG Performance Status of 0, 1, or 2.
  • Patients must have adequate renal function and serum creatinine ≤2.0 mg/dL.
  • Patients must have adequate liver function as defined by total bilirubin ≤2.0 mg/dL and transaminase levels no higher than 3.0 times the institution's upper limit of normal (ULN). Patients with hepatic metastases may have transaminase levels of up to 5.0 times the ULN.
  • All patients must have a serum albumin ≥3.0 g/dL.
  • Patients must have adequate bone marrow (BM) function as defined by a granulocyte count ≥1,500/mm3, a platelet count ≥100,000/mm3, and hemoglobin >9 g/dL.
  • Disease-free period of more than 5 years from prior malignancies other than pancreas (except curatively treated basal cell carcinoma, squamous cell carcinoma of the skin, or carcinoma in situ of the cervix and ductal carcinoma in situ [DCIS] breast disease).
  • Adequate contraceptive regimen (including prescription oral contraceptives [birth control pills], contraceptive injections, intrauterine device [IUD], double-barrier method [spermicidal jelly or foam with condoms or diaphragm], contraceptive patch, or surgical sterilization) before entry and throughout the study for female patients of reproductive potential or female partners of male patients.
  • Female patient with reproductive potential must have a negative urine beta human chorionic gonadotropin (bHCG) pregnancy test at Screening.
  • Willing to adhere to the prohibitions and restrictions specified in this protocol.
  • Patient must have signed an informed consent document.

Exclusion Criteria:

  • Patients with unresectable locally advanced disease without evidence of disease elsewhere.
  • Life expectancy of less than 12 weeks.
  • Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, uncontrolled hypertension or seizure disorder.
  • Active infection not adequately responding to appropriate therapy.
  • Symptomatic or clinically evident ascites.
  • Serum sodium less than 130 mEq/L or conditions that may predispose patients to hyponatremia.
  • Female patients who are pregnant or lactating.
  • Male patients with female sexual partners who are unwilling to follow the strict contraception requirements described in this protocol.
  • Major surgery without full recovery or major surgery within 3 weeks of ON 01910.Na treatment start.
  • Evidence of brain metastases.
  • Any concurrent administration and/or prior administration within 4 weeks of the first dose of study drug, of radiotherapy, or immunotherapy.
  • Psychiatric illness/social situations that would limit the patient's ability to tolerate and/or comply with study requirements, or inability to comply with study and/or follow-up procedures (e.g., drug addition, chronic non-compliance, etc.).
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01360853

  Hide Study Locations
Locations
United States, California
UCSD Moores Cancer Center
La Jolla, California, United States, 92037
Desert Comprehensive Cancer Center
Palm Springs, California, United States, 92262
Pacific Cancer Care
Salinas, California, United States, 93901
Premiere Oncology
Santa Monica, California, United States, 90404
United States, Colorado
University of Colorado Cancer Center
Aurora, Colorado, United States, 80045
Kaiser Permanente Colorado
Denver, Colorado, United States, 80205
Poudre Valley Cancer Center of the Rockies
Fort Collins, Colorado, United States, 80528
United States, Connecticut
Yale Cancer Center
New Haven, Connecticut, United States, 06519
United States, Florida
Mount Sinai Comprehensive Cancer Center
Miami Beach, Florida, United States, 33140
United States, Hawaii
University of Hawaii Cancer Center
Honolulu, Hawaii, United States, 96813
United States, Kansas
University of Kansas Cancer Center
Westwood, Kansas, United States, 66205
United States, Massachusetts
UMASS Medical School
Worcester, Massachusetts, United States, 01655
United States, Michigan
Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
United States, Montana
Billings Clinic Cancer Center
Billings, Montana, United States, 59101
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
New York University Langone Medical Center
New York, New York, United States, 10016
University of Rochester Medical Center
Rochester, New York, United States, 14642
United States, North Carolina
University of North Carolina Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, United States, 27599
Levine Cancer Institute
Charlotte, North Carolina, United States, 28204
Cone Health Cancer Center
Greensboro, North Carolina, United States, 27403
Hendersonville Hematology and Oncology at Pardee
Hendersonville, North Carolina, United States, 28971
Rex Cancer Center UNC Healthcare
Raleigh, North Carolina, United States, 27607
United States, North Dakota
St. Alexis Medical Center-Mid Dakota Clinic PC
Bismarck, North Dakota, United States, 58501
United States, Ohio
University of Cincinnati Cancer Center
Cincinnati, Ohio, United States, 45219
United States, Oregon
Kaiser Permanente NW
Portland, Oregon, United States, 97227
United States, Pennsylvania
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111
United States, South Carolina
Medical University of South Carolina - Hollings Cancer Center
Charleston, South Carolina, United States, 29425
McLeod Regional Medical Center
Florence, South Carolina, United States, 29506
United States, Tennessee
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232
United States, Washington
Seattle Cancer Care Alliance
Seattle, Washington, United States, 98109
Hungary
Semmelweis University Department of Diagnostic Radiology and Oncotherapy
Budapest, Hungary, 1078
Semmelweis University, 3rd Department of Internal Medicine
Budapest, Hungary, 1125
Hetenyi Geza Hospital 5004, Szolnok, Hungary
Szolnok, Hungary, 5004
India
Basavatarakam Indo-American Cancer Hospital
Hyderabad, Andhra Pradesh, India, 500034
Regional Cancer Center
Thiruvananthapuram, Kerala, India, 695001
Jaslok Hospital & Research Centre
Mumbai, Maharashtra, India, 400026
Shatabdi Superspeciality Hospital
Nashik, Maharashtra, India, 422005
Ruby Hall Clinic
Pune, Maharashtra, India, 411001
Lifeline Multispeciality Hospitals
Chennai, Tamil Nadu, India, 600096
Russian Federation
State Budget Medical Institution of the Arkhangelsk Region
Arkhangelsk, Russian Federation, 163045
Chelyabinsk Regional Clinical Oncology Center
Chelyabinsk, Russian Federation, 454087
State Budget Medical Institution Clinical Oncology Center 1
Krasnodar, Russian Federation, 350040
Budget Medical Institution of the Omsk Region: Clinical Oncology Center
Omsk, Russian Federation, 644013
State Budget Medical Institution: Leningrad Regional Clinical Hospital
Saint Petersburg, Russian Federation, 194291
State Medical Institution: Tula Regional Oncology Center
Tula, Russian Federation, 300053
Ukraine
Zakarpattia Regional Clinical Oncology Center Department of Chemotherapy
Uzhhorod, Ukraine, 88014
Sponsors and Collaborators
Onconova Therapeutics, Inc.
Academic Oncology Gastrointestinal Cancer Consortium (AGICC)
Investigators
Study Chair: Wells Messersmith, MD Anschutz Cancer Pavilion
Study Chair: Lawrence P. Leichman, MD Academic Oncology Gastrointestinal Cancer Consortium
Study Chair: Antonio Jimeno, MD, PhD Anschutz Cancer Pavilion
  More Information

Additional Information:
Publications:
Responsible Party: Onconova Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT01360853     History of Changes
Other Study ID Numbers: 04-22, 11PAN01
Study First Received: May 24, 2011
Last Updated: August 27, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Onconova Therapeutics, Inc.:
pancreatic cancer
gemcitabine
ON 01910.Na
rigosertib sodium

Additional relevant MeSH terms:
Gemcitabine
Adenocarcinoma
Pancreatic Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on April 23, 2014