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

Study Overview

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

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.

N/A

Metastatic or Locally Advanced Unresectable Pancreatic Adenocarcinoma

DRUG: TH-302
DRUG: Gemcitabine
DRUG: Placebo (5 percent dextrose - D5W)

EMR 200592-001
2012-002957-42 (EUDRACT_NUMBER Identifier) (EUDRACT_NUMBER: )

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2012-12-07	Results First Submitted 2017-07-18	Last Update Submitted that met QC Criteria 2025-05-08
First Submitted that Met QC Criteria 2012-12-07	Results First Submitted that Met QC Criteria 2017-10-26	Last Update Posted (ACTUAL) 2025-05-11
First Posted (ACTUAL) 2012-12-11	Results First Posted 2017-12-02	Last Verified 2017-10

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Randomized

Interventional Model:
Parallel

Masking:
Double

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
ACTIVE_COMPARATOR: Gemcitabine plus TH-302	DRUG: TH-302 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 s DRUG: Gemcitabine 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.
PLACEBO_COMPARATOR: Gemcitabine plus placebo	DRUG: Gemcitabine 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. DRUG: Placebo (5 percent dextrose - D5W) 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.

Participant Group/Arm

Intervention/Treatment

ACTIVE_COMPARATOR: Gemcitabine plus TH-302

DRUG: TH-302

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 s

DRUG: Gemcitabine

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.

PLACEBO_COMPARATOR: Gemcitabine plus placebo

DRUG: Gemcitabine

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.

DRUG: Placebo (5 percent dextrose - D5W)

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.

Primary Outcome Measures	Measure Description	Time Frame
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 Outcome Measures	Measure Description	Time Frame
Progression Free Survival	Progression Free Survival is defined as the time from randomization to either first observation of progressive disease or occurrence of death. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.	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

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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
Other protocol defined inclusion criteria may apply

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
Other protocol defined exclusion criteria may apply

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Threshold Pharmaceuticals

Investigators

STUDY_DIRECTOR: Antonio Gualberto, MD, PhD, EMD Serono Inc., a subsidiary of Merck KGaA, Darmstadt, Germany

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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.

Learn

Resources

PatientS

Caregivers

Clinical Trial Record