Clinical Trial Testing TH-302 in Combination With Gemcitabine in Previously Untreated Subjects With Metastatic or Locally Advanced Unresectable Pancreatic Adenocarcinoma

NCT01746979 | Completed Phase 3 Results DMC

• 2 other identifiers: EMR 200592-0012012-002957-42
• Study Type: interventional
• Target: 693
• Locations: 2 countries
• Sites: 2

Brief Summary

This Phase 3 trial is a randomized, double-blind, placebo-controlled trial of gemcitabine in combination with TH-302 compared to gemcitabine in combination with placebo in subjects with locally advanced unresectable or metastatic pancreatic adenocarcinoma. Randomized subjects will receive TH-302 plus gemcitabine or gemcitabine plus placebo in 4-week cycles until there is evidence of progressive disease, intolerable toxicity, or the subject discontinues from the trial for other reasons (for example, withdrawal of consent). The primary efficacy endpoint is overall survival (OS) time. The data cut-off for statistical analyses of the primary and secondary endpoints will be reached when 508 events (deaths) will be reported. No planned interim analyses will be conducted. An Independent Safety Monitoring Board (ISMB) will provide periodic evaluations of the unblinded safety data to ensure subject safety and the validity and scientific merit of the study. A total of 660 subjects will be enrolled.

Conditions

Metastatic or Locally Advanced Unresectable Pancreatic Adenocarcinoma

Keywords

TH-302; Evofosfamide; Pancreatic Cancer; EMR200592-001

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  Overall survival is defined as time from randomization to death or last day known to be alive.

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years

Secondary Outcomes (1)

• Progression Free Survival

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years

Study Arms (2)

Gemcitabine plus TH-302

ACTIVE COMPARATOR

Drug: TH-302; Drug: Gemcitabine

Gemcitabine plus placebo

PLACEBO COMPARATOR

Drug: Gemcitabine; Drug: Placebo (5 percent dextrose - D5W)

Interventions

TH-302 DRUG

TH-302 will be administered at a dose of 340 milligrams per square meter (mg/m\^2) as intravenous infusion over 30 minutes on Day 1, 8 and 15 of every 28-day cycle. Doses will be administered until evidence of progressive disease, intolerable toxicity or subject withdrawal.

Gemcitabine plus TH-302

Gemcitabine DRUG

Gemcitabine will be administered at a dose of 1000 (mg/m\^2) as intravenous infusion over 30 minutes on Day 1, 8 and 15 of every 28-day cycle. Doses will be administered until evidence of progressive disease, intolerable toxicity or subject withdrawal.

Gemcitabine plus TH-302; Gemcitabine plus placebo

Placebo (5 percent dextrose - D5W) DRUG

TH-302 placebo (5 percent dextrose - D5W) will be administered as intravenous infusion over 30 minutes on Day 1, 8 and 15 of every 28-day cycle. Doses will be administered until evidence of progressive disease, intolerable toxicity or subject withdrawal.

Gemcitabine plus placebo

Eligibility Criteria

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

You may qualify if:

• At least 18 years of age
• Locally advanced unresectable or metastatic pancreatic ductal adenocarcinoma proven by histology or cytology and previously untreated with chemotherapy or systemic therapy other than:
• Radiosensitizing doses of 5-fluorouracil;
• Radiosensitizing doses of gemcitabine if relapse occurred at least 6 months after completion of gemcitabine;
• Neoadjuvant chemotherapy if relapse occurred at least 6 months after surgical resection;
• Adjuvant chemotherapy if relapse occurred at least 6 months after completion of adjuvant chemotherapy
• Measurable disease (at least one target lesion outside of previous radiation fields) or non-measurable disease by RECIST v.1.1 criteria
• Documentation of disease progression since any prior therapy
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Life expectancy of at least 3 month
• Acceptable liver, renal function and acceptable hematological status

You may not qualify if:

• New York Heart Association (NYHA) Class III or IV congestive heart failure, myocardial infarction within 6 months prior to the date of randomization, unstable arrhythmia or symptomatic peripheral arterial vascular disease
• Symptomatic ischemic heart disease
• Known brain, leptomeningeal or epidural metastases (unless treated and well controlled for at least 3 months)
• Previous malignancy other than pancreatic cancer in the last 5 years, except for adequately treated non-melanoma skin cancer or pre-invasive cancer of the cervix
• Severe chronic obstructive or other pulmonary disease with hypoxemia
• Major surgery, other than diagnostic surgery, less than or equal to 28 days prior to the date of randomization. Subject must have completely recovered from surgery
• Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy
• Treatment of pancreatic cancer with radiation therapy or surgery less than or equal to 28 days prior to the date of randomization
• Prior therapy with a hypoxic cytotoxin
• Subjects who participated in an investigational drug or device trial less than or equal to 28 days prior to Day 1 of the first cycle
• Known infection with Human Immunodeficiency Virus (HIV), or an active infection with Hepatitis B or Hepatitis C
• Subjects who have exhibited allergic reactions to a structural compound similar to TH-302 or the drug product excipients or to gemcitabine or its excipients

Sponsors & Collaborators

• ImmunoGenesis: lead
• Threshold Pharmaceuticals: collaborator

Study Sites (2)

Please Contact U.S. Medical Information

Rockland, Massachusetts, United States

Location

Please Contact Merck Communication Center

Darmstadt, Germany

Location

Related Publications (1)

• Borad MJ, Reddy SG, Bahary N, Uronis HE, Sigal D, Cohn AL, Schelman WR, Stephenson J Jr, Chiorean EG, Rosen PJ, Ulrich B, Dragovich T, Del Prete SA, Rarick M, Eng C, Kroll S, Ryan DP. Randomized Phase II Trial of Gemcitabine Plus TH-302 Versus Gemcitabine in Patients With Advanced Pancreatic Cancer. J Clin Oncol. 2015 May 1;33(13):1475-81. doi: 10.1200/JCO.2014.55.7504. Epub 2014 Dec 15.

  PMID: 25512461 DERIVED

MeSH Terms

Conditions

Neoplasm Metastasis; Pancreatic Neoplasms

Interventions

TH 302; Gemcitabine

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Digestive System Neoplasms; Neoplasms by Site; 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

Results Point of Contact

• Title: Thomas Wilson
• Organization: Threshold Pharmaceuticals

twilson@thresholdpharm.com

302-359-0565

Study Officials

• Antonio Gualberto, MD, PhD

  EMD Serono Inc., a subsidiary of Merck KGaA, Darmstadt, Germany

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 7, 2012
• First Posted: December 11, 2012
• Study Start: December 1, 2012
• Primary Completion: February 1, 2016
• Study Completion: May 1, 2016
• Last Updated: May 11, 2025
• Results First Posted: December 2, 2017

Record last verified: 2017-10

Locations

DE (1); US (1)