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

NCT ID: NCT01360853

Last Updated: 2016-08-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 160 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-05-31
• Study Completion Date: 2015-12-31

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.

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.

Conditions

Metastatic Pancreatic Adenocarcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

ON 01910.Na

Intervention Type: DRUG

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

Gemcitabine

Intervention Type: DRUG

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

Arm B: Gemcitabine only

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

Group Type: ACTIVE_COMPARATOR

Gemcitabine

Intervention Type: DRUG

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

Interventions

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.

Intervention Type: DRUG

Gemcitabine

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

Intervention Type: DRUG

Gemcitabine

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

Intervention Type: DRUG

Other Intervention Names

rigosertib sodium; Gemzar; Gemcitabine HCl; Gemzar; Gemcitabine HCl

Eligibility 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.).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Academic GI Cancer Consortium (AGICC)

OTHER

Sponsor Role: collaborator

Traws Pharma, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Wells Messersmith, MD

Role: STUDY_CHAIR

Anschutz Cancer Pavilion

Lawrence P. Leichman, MD

Role: STUDY_CHAIR

Academic Oncology Gastrointestinal Cancer Consortium

Antonio Jimeno, MD, PhD

Role: STUDY_CHAIR

Anschutz Cancer Pavilion

Locations

UCSD Moores Cancer Center

La Jolla, California, United States

Desert Comprehensive Cancer Center

Palm Springs, California, United States

Pacific Cancer Care

Salinas, California, United States

Premiere Oncology

Santa Monica, California, United States

University of Colorado Cancer Center

Aurora, Colorado, United States

Kaiser Permanente Colorado

Denver, Colorado, United States

Poudre Valley Cancer Center of the Rockies

Fort Collins, Colorado, United States

Yale Cancer Center

New Haven, Connecticut, United States

Mount Sinai Comprehensive Cancer Center

Miami Beach, Florida, United States

University of Hawaii Cancer Center

Honolulu, Hawaii, United States

University of Kansas Cancer Center

Westwood, Kansas, United States

UMASS Medical School

Worcester, Massachusetts, United States

Karmanos Cancer Institute

Detroit, Michigan, United States

Billings Clinic Cancer Center

Billings, Montana, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

New York University Langone Medical Center

New York, New York, United States

University of Rochester Medical Center

Rochester, New York, United States

University of North Carolina Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, United States

Levine Cancer Institute

Charlotte, North Carolina, United States

Cone Health Cancer Center

Greensboro, North Carolina, United States

Hendersonville Hematology and Oncology at Pardee

Hendersonville, North Carolina, United States

Rex Cancer Center UNC Healthcare

Raleigh, North Carolina, United States

St. Alexis Medical Center-Mid Dakota Clinic PC

Bismarck, North Dakota, United States

University of Cincinnati Cancer Center

Cincinnati, Ohio, United States

Kaiser Permanente NW

Portland, Oregon, United States

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Medical University of South Carolina - Hollings Cancer Center

Charleston, South Carolina, United States

McLeod Regional Medical Center

Florence, South Carolina, United States

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

Seattle Cancer Care Alliance

Seattle, Washington, United States

Semmelweis University Department of Diagnostic Radiology and Oncotherapy

Budapest, , Hungary

Semmelweis University, 3rd Department of Internal Medicine

Budapest, , Hungary

Hetenyi Geza Hospital 5004, Szolnok, Hungary

Szolnok, , Hungary

Basavatarakam Indo-American Cancer Hospital

Hyderabad, Andhra Pradesh, India

Regional Cancer Center

Thiruvananthapuram, Kerala, India

Jaslok Hospital & Research Centre

Mumbai, Maharashtra, India

Shatabdi Superspeciality Hospital

Nashik, Maharashtra, India

Ruby Hall Clinic

Pune, Maharashtra, India

Lifeline Multispeciality Hospitals

Chennai, Tamil Nadu, India

State Budget Medical Institution of the Arkhangelsk Region

Arkhangelsk, , Russia

Chelyabinsk Regional Clinical Oncology Center

Chelyabinsk, , Russia

State Budget Medical Institution Clinical Oncology Center 1

Krasnodar, , Russia

Budget Medical Institution of the Omsk Region: Clinical Oncology Center

Omsk, , Russia

State Budget Medical Institution: Leningrad Regional Clinical Hospital

Saint Petersburg, , Russia

State Medical Institution: Tula Regional Oncology Center

Tula, , Russia

Zakarpattia Regional Clinical Oncology Center Department of Chemotherapy

Uzhhorod, , Ukraine

Countries

United States; Hungary; India; Russia; Ukraine

References

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.

Reference Type: BACKGROUND

PMID: 19029951 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 18955447 (View on PubMed)

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.

Reference Type: RESULT

PMID: 26945010 (View on PubMed)

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.

Reference Type: RESULT

PMID: 26489442 (View on PubMed)

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.

Reference Type: RESULT

PMID: 26091808 (View on PubMed)

Related Links

http://www.agicc.org

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

Other Identifiers

11PAN01

Identifier Type: OTHER

Identifier Source: secondary_id

04-22

Identifier Type: -

Identifier Source: org_study_id