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

NCT01360853 | Completed Phase 3 DMC

• 2 other identifiers: 04-2211PAN01
• Study Type: interventional
• Target: 160
• Locations: 5 countries
• Sites: 46

Brief Summary

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.

Conditions

Metastatic Pancreatic Adenocarcinoma

Keywords

pancreatic cancer; gemcitabine; ON 01910.Na; rigosertib sodium

Outcome Measures

Primary Outcomes (1)

• Survival

  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.

  18 months

Secondary Outcomes (7)

• Progression-free survival

  18 months

• Tumor size

  18 months

• Safety/tolerability

  18 months

• QOL questionnaire

  18 months

• Biomarkers

  18 months

Study Arms (2)

Arm A: Combination

EXPERIMENTAL

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; Drug: Gemcitabine

Arm B: Gemcitabine only

ACTIVE COMPARATOR

Arm B: Gemcitabine only, 1000 mg/m2 weekly for 3 weeks of a 4 week cycle.

Drug: Gemcitabine

Interventions

ON 01910.Na DRUG

ON 01910.Na, 1800 mg/m2 via 2 hr CIV infusions administered twice weekly for 3 weeks of a 4 week cycle.

Also known as: rigosertib sodium

Arm A: Combination

Gemcitabine DRUG

Gemcitabine 1000 mg/m2 weekly for 3 weeks of a 4 week cycle.

Also known as: Gemzar, Gemcitabine HCl

Arm A: Combination

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.).

Sponsors & Collaborators

• Traws Pharma, Inc.: lead
• Academic GI Cancer Consortium (AGICC): collaborator

Study Sites (46)

UCSD Moores Cancer Center

La Jolla, California, 92037, United States

Location

Desert Comprehensive Cancer Center

Palm Springs, California, 92262, United States

Location

Pacific Cancer Care

Salinas, California, 93901, United States

Location

Premiere Oncology

Santa Monica, California, 90404, United States

Location

University of Colorado Cancer Center

Aurora, Colorado, 80045, United States

Location

Kaiser Permanente Colorado

Denver, Colorado, 80205, United States

Location

Poudre Valley Cancer Center of the Rockies

Fort Collins, Colorado, 80528, United States

Location

Yale Cancer Center

New Haven, Connecticut, 06519, United States

Location

Mount Sinai Comprehensive Cancer Center

Miami Beach, Florida, 33140, United States

Location

University of Hawaii Cancer Center

Honolulu, Hawaii, 96813, United States

Location

University of Kansas Cancer Center

Westwood, Kansas, 66205, United States

Location

UMASS Medical School

Worcester, Massachusetts, 01655, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Billings Clinic Cancer Center

Billings, Montana, 59101, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

New York University Langone Medical Center

New York, New York, 10016, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

University of North Carolina Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

Location

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

Cone Health Cancer Center

Greensboro, North Carolina, 27403, United States

Location

Hendersonville Hematology and Oncology at Pardee

Hendersonville, North Carolina, 28971, United States

Location

Rex Cancer Center UNC Healthcare

Raleigh, North Carolina, 27607, United States

Location

St. Alexis Medical Center-Mid Dakota Clinic PC

Bismarck, North Dakota, 58501, United States

Location

University of Cincinnati Cancer Center

Cincinnati, Ohio, 45219, United States

Location

Kaiser Permanente NW

Portland, Oregon, 97227, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Medical University of South Carolina - Hollings Cancer Center

Charleston, South Carolina, 29425, United States

Location

McLeod Regional Medical Center

Florence, South Carolina, 29506, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

Semmelweis University Department of Diagnostic Radiology and Oncotherapy

Budapest, 1078, Hungary

Location

Semmelweis University, 3rd Department of Internal Medicine

Budapest, 1125, Hungary

Location

Hetenyi Geza Hospital 5004, Szolnok, Hungary

Szolnok, 5004, Hungary

Location

Basavatarakam Indo-American Cancer Hospital

Hyderabad, Andhra Pradesh, 500034, India

Location

Regional Cancer Center

Thiruvananthapuram, Kerala, 695001, India

Location

Jaslok Hospital & Research Centre

Mumbai, Maharashtra, 400026, India

Location

Shatabdi Superspeciality Hospital

Nashik, Maharashtra, 422005, India

Location

Ruby Hall Clinic

Pune, Maharashtra, 411001, India

Location

Lifeline Multispeciality Hospitals

Chennai, Tamil Nadu, 600096, India

Location

State Budget Medical Institution of the Arkhangelsk Region

Arkhangelsk, 163045, Russia

Location

Chelyabinsk Regional Clinical Oncology Center

Chelyabinsk, 454087, Russia

Location

State Budget Medical Institution Clinical Oncology Center 1

Krasnodar, 350040, Russia

Location

Budget Medical Institution of the Omsk Region: Clinical Oncology Center

Omsk, 644013, Russia

Location

State Budget Medical Institution: Leningrad Regional Clinical Hospital

Saint Petersburg, 194291, Russia

Location

State Medical Institution: Tula Regional Oncology Center

Tula, 300053, Russia

Location

Zakarpattia Regional Clinical Oncology Center Department of Chemotherapy

Uzhhorod, 88014, Ukraine

Location

Related Publications (5)

• Jimeno A, Chan A, Cusatis G, Zhang X, Wheelhouse J, Solomon A, Chan F, Zhao M, Cosenza SC, Ramana Reddy MV, Rudek MA, Kulesza P, Donehower RC, Reddy EP, Hidalgo M. Evaluation of the novel mitotic modulator ON 01910.Na in pancreatic cancer and preclinical development of an ex vivo predictive assay. Oncogene. 2009 Jan 29;28(4):610-8. doi: 10.1038/onc.2008.424. Epub 2008 Nov 24.

  PMID: 19029951 BACKGROUND

• Jimeno A, Li J, Messersmith WA, Laheru D, Rudek MA, Maniar M, Hidalgo M, Baker SD, Donehower RC. Phase I study of ON 01910.Na, a novel modulator of the Polo-like kinase 1 pathway, in adult patients with solid tumors. J Clin Oncol. 2008 Dec 1;26(34):5504-10. doi: 10.1200/JCO.2008.17.9788. Epub 2008 Oct 27.

  PMID: 18955447 BACKGROUND

• O'Neil BH, Scott AJ, Ma WW, Cohen SJ, Aisner DL, Menter AR, Tejani MA, Cho JK, Granfortuna J, Coveler AL, Olowokure OO, Baranda JC, Cusnir M, Phillip P, Boles J, Nazemzadeh R, Rarick M, Cohen DJ, Radford J, Fehrenbacher L, Bajaj R, Bathini V, Fanta P, Berlin J, McRee AJ, Maguire R, Wilhelm F, Maniar M, Jimeno A, Gomes CL, Messersmith WA. A phase II/III randomized study to compare the efficacy and safety of rigosertib plus gemcitabine versus gemcitabine alone in patients with previously untreated metastatic pancreatic cancer. Ann Oncol. 2016 Jun;27(6):1180. doi: 10.1093/annonc/mdw095. Epub 2016 Mar 3. No abstract available.

  PMID: 26945010 RESULT

• O'Neil BH, Scott AJ, Ma WW, Cohen SJ, Leichman L, Aisner DL, Menter AR, Tejani MA, Cho JK, Granfortuna J, Coveler L, Olowokure OO, Baranda JC, Cusnir M, Phillip P, Boles J, Nazemzadeh R, Rarick M, Cohen DJ, Radford J, Fehrenbacher L, Bajaj R, Bathini V, Fanta P, Berlin J, McRee AJ, Maguire R, Wilhelm F, Maniar M, Jimeno A, Gomes CL, Messersmith WA. A phase II/III randomized study to compare the efficacy and safety of rigosertib plus gemcitabine versus gemcitabine alone in patients with previously untreated metastatic pancreatic cancer. Ann Oncol. 2015 Dec;26(12):2505. doi: 10.1093/annonc/mdv477. Epub 2015 Oct 21. No abstract available.

  PMID: 26489442 RESULT

• O'Neil BH, Scott AJ, Ma WW, Cohen SJ, Aisner DL, Menter AR, Tejani MA, Cho JK, Granfortuna J, Coveler L, Olowokure OO, Baranda JC, Cusnir M, Phillip P, Boles J, Nazemzadeh R, Rarick M, Cohen DJ, Radford J, Fehrenbacher L, Bajaj R, Bathini V, Fanta P, Berlin J, McRee AJ, Maguire R, Wilhelm F, Maniar M, Jimeno A, Gomes CL, Messersmith WA. A phase II/III randomized study to compare the efficacy and safety of rigosertib plus gemcitabine versus gemcitabine alone in patients with previously untreated metastatic pancreatic cancer. Ann Oncol. 2015 Sep;26(9):1923-1929. doi: 10.1093/annonc/mdv264. Epub 2015 Jun 19.

  PMID: 26091808 RESULT

Related Links

• Related information about Academic Oncology Gastrointestinal Cancer Consortium (AGICC).

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

ON 01910; Gemcitabine

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• 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

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 24, 2011
• First Posted: May 26, 2011
• Study Start: May 1, 2011
• Primary Completion: June 1, 2015
• Study Completion: December 1, 2015
• Last Updated: August 4, 2016

Record last verified: 2016-08

Locations

US (30); RU (6); UA (1); IN (6); HU (3)