Gemcitabine and ON 01910.Na in Previously Untreated Metastatic Pancreatic Cancer (ONTRAC)
This study is currently recruiting participants.
Verified January 2013 by Onconova Therapeutics, Inc.
Sponsor:
Onconova Therapeutics, Inc.
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: January 21, 2013
Last verified: January 2013
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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:
|
|
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:
|
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
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Contacts
| Contact: Francois E. Wilhelm, MD, PhD | (888) 338-3130 | fwilhelm@onconova.us |
Hide Study LocationsLocations
| United States, California | |
| UCSD Moores Cancer Center | Recruiting |
| La Jolla, California, United States, 92037 | |
| Principal Investigator: Paul Fanta, MD | |
| Desert Comprehensive Cancer Center | Recruiting |
| Palm Springs, California, United States, 92262 | |
| Principal Investigator: Lawrence P. Leichman, MD | |
| Pacific Cancer Care | Recruiting |
| Salinas, California, United States, 93901 | |
| Principal Investigator: Laura Stampleman, MD | |
| Premiere Oncology | Not yet recruiting |
| Santa Monica, California, United States, 90404 | |
| Principal Investigator: Lee Rosen, MD | |
| United States, Colorado | |
| University of Colorado Cancer Center | Recruiting |
| Aurora, Colorado, United States, 80045 | |
| Principal Investigator: Wells A. Messersmith, MD | |
| Kaiser Permanente Colorado | Recruiting |
| Denver, Colorado, United States, 80205 | |
| Principal Investigator: Alex Menter, MD | |
| Poudre Valley Cancer Center of the Rockies | Recruiting |
| Fort Collins, Colorado, United States, 80528 | |
| Principal Investigator: Robert Marschke, MD | |
| United States, Connecticut | |
| Yale Cancer Center | Recruiting |
| New Haven, Connecticut, United States, 06519 | |
| Principal Investigator: Howard S. Hochster, MD | |
| United States, Florida | |
| Mount Sinai Comprehensive Cancer Center | Recruiting |
| Miami Beach, Florida, United States, 33140 | |
| Principal Investigator: Mike Cusnir, MD | |
| United States, Hawaii | |
| University of Hawaii Cancer Center | Recruiting |
| Honolulu, Hawaii, United States, 96813 | |
| Principal Investigator: Jonathan Cho, MD | |
| United States, Kansas | |
| University of Kansas Cancer Center | Recruiting |
| Westwood, Kansas, United States, 66205 | |
| Principal Investigator: Joaquina C. Baranda, MD | |
| United States, Massachusetts | |
| UMASS Medical School | Recruiting |
| Worcester, Massachusetts, United States, 01655 | |
| Principal Investigator: Venu Gopal Bathini, MD | |
| United States, Michigan | |
| Karmanos Cancer Institute | Recruiting |
| Detroit, Michigan, United States, 48201 | |
| Principal Investigator: Philip A. Philip, MD, PhD | |
| United States, Montana | |
| Billings Clinic Cancer Center | Recruiting |
| Billings, Montana, United States, 59101 | |
| Principal Investigator: Robert Geller, MD | |
| United States, New York | |
| Roswell Park Cancer Institute | Recruiting |
| Buffalo, New York, United States, 14263 | |
| Principal Investigator: Wen Wee Ma, MD | |
| New York University Langone Medical Center | Recruiting |
| New York, New York, United States, 10016 | |
| Principal Investigator: Deirdre Cohen, MD | |
| University of Rochester Medical Center | Recruiting |
| Rochester, New York, United States, 14642 | |
| Principal Investigator: Mohamed Tejani, MD | |
| United States, North Carolina | |
| University of North Carolina Lineberger Comprehensive Cancer Center | Recruiting |
| Chapel Hill, North Carolina, United States, 27599 | |
| Principal Investigator: Bert O'Neil, MD | |
| Levine Cancer Institute | Recruiting |
| Charlotte, North Carolina, United States, 28204 | |
| Principal Investigator: Reza Nazemzadeh, MD | |
| Cone Health Cancer Center | Recruiting |
| Greensboro, North Carolina, United States, 27403 | |
| Principal Investigator: Peter Rubin, MD | |
| Hendersonville Hematology and Oncology at Pardee | Recruiting |
| Hendersonville, North Carolina, United States, 28971 | |
| Principal Investigator: James Radford, MD | |
| Rex Cancer Center UNC Healthcare | Recruiting |
| Raleigh, North Carolina, United States, 27607 | |
| Principal Investigator: Jeremiah Boles, MD | |
| United States, North Dakota | |
| St. Alexis Medical Center-Mid Dakota Clinic PC | Recruiting |
| Bismarck, North Dakota, United States, 58501 | |
| Principal Investigator: Jayaram S. Bharadwaj, MD | |
| United States, Ohio | |
| University of Cincinnati Cancer Center | Recruiting |
| Cincinnati, Ohio, United States, 45219 | |
| Principal Investigator: Olugbenga Olowokure, MD | |
| United States, Oregon | |
| Kaiser Permanente NW | Recruiting |
| Portland, Oregon, United States, 97227 | |
| Principal Investigator: Mark U. Rarick, MD | |
| United States, Pennsylvania | |
| Fox Chase Cancer Center | Recruiting |
| Philadelphia, Pennsylvania, United States, 19111 | |
| Principal Investigator: Steven Cohen, MD | |
| United States, South Carolina | |
| Medical University of South Carolina - Hollings Cancer Center | Recruiting |
| Charleston, South Carolina, United States, 29425 | |
| Principal Investigator: Steven Chin, MD | |
| McLeod Regional Medical Center | Recruiting |
| Florence, South Carolina, United States, 29506 | |
| Principal Investigator: Rajeesh Bajaj, MD | |
| United States, Tennessee | |
| Vanderbilt-Ingram Cancer Center | Recruiting |
| Nashville, Tennessee, United States, 37232 | |
| Principal Investigator: Jordan Berlin, MD | |
| United States, Washington | |
| Seattle Cancer Care Alliance | Recruiting |
| Seattle, Washington, United States, 98109 | |
| Principal Investigator: Andrew Coveler, MD | |
| Hungary | |
| Semmelweis University Department of Diagnostic Radiology and Oncotherapy | Recruiting |
| Budapest, Hungary, 1078 | |
| Principal Investigator: Magdolna Dank, MD | |
| Semmelweis University, 3rd Department of Internal Medicine | Recruiting |
| Budapest, Hungary, 1125 | |
| Principal Investigator: Judit Kocsis, MD | |
| Hetenyi Geza Hospital 5004, Szolnok, Hungary | Recruiting |
| Szolnok, Hungary, 5004 | |
| Principal Investigator: Tibor Csőszi, MD | |
| India | |
| Basavatarakam Indo-American Cancer Hospital | Active, not recruiting |
| Hyderabad, Andhra Pradesh, India, 500034 | |
| Regional Cancer Center | Active, not recruiting |
| Thiruvananthapuram, Kerala, India, 695001 | |
| Jaslok Hospital & Research Centre | Active, not recruiting |
| Mumbai, Maharashtra, India, 400026 | |
| Shatabdi Superspeciality Hospital | Active, not recruiting |
| Nashik, Maharashtra, India, 422005 | |
| Ruby Hall Clinic | Active, not recruiting |
| Pune, Maharashtra, India, 411001 | |
| Lifeline Multispeciality Hospitals | Active, not recruiting |
| Chennai, Tamil Nadu, India, 600096 | |
| Russian Federation | |
| State Budget Medical Institution of the Arkhangelsk Region | Recruiting |
| Arkhangelsk, Russian Federation, 163045 | |
| Principal Investigator: Lyudmila N. Lebedeva, MD | |
| Chelyabinsk Regional Clinical Oncology Center | Recruiting |
| Chelyabinsk, Russian Federation, 454087 | |
| Principal Investigator: Oleg A. Gladkov, MD | |
| State Budget Medical Institution Clinical Oncology Center 1 | Recruiting |
| Krasnodar, Russian Federation, 350040 | |
| Principal Investigator: Irina S. Davidenko, MD | |
| Budget Medical Institution of the Omsk Region: Clinical Oncology Center | Recruiting |
| Omsk, Russian Federation, 644013 | |
| Principal Investigator: Eduard M. Pshevlotsky, MD | |
| State Budget Medical Institution: Leningrad Regional Clinical Hospital | Recruiting |
| Saint Petersburg, Russian Federation, 194291 | |
| Principal Investigator: Andrey S. Pryadko, MD | |
| State Medical Institution: Tula Regional Oncology Center | Recruiting |
| Tula, Russian Federation, 300053 | |
| Principal Investigator: Igor V. Pimenov, MD | |
| Ukraine | |
| Zakarpattia Regional Clinical Oncology Center Department of Chemotherapy | Recruiting |
| Uzhhorod, Ukraine, 88014 | |
| Principal Investigator: Andril V. Rusyn, MD, PhD | |
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: | January 21, 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:
|
Adenocarcinoma Adenocarcinoma, Mucinous Pancreatic Neoplasms Carcinoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Neoplasms, Cystic, Mucinous, and Serous Digestive System Neoplasms Neoplasms by Site Endocrine Gland Neoplasms Digestive System Diseases Pancreatic Diseases Endocrine System Diseases |
Gemcitabine 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 May 16, 2013