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 8, 2014
Last verified: August 2014
  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: June 2015
Estimated Primary Completion Date: December 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01360853

  Show 46 Study Locations
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 8, 2014
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
Pancreatic Neoplasms
Carcinoma
Digestive System Diseases
Digestive System Neoplasms
Endocrine Gland Neoplasms
Endocrine System Diseases
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Pancreatic Diseases
Gemcitabine
Anti-Infective Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antiviral Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014