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

May 8, 2025 updated by: ImmunoGenesis

A Randomized, Double-Blind, Phase III Study of the Efficacy and Safety of Gemcitabine in Combination With TH-302 Compared With Gemcitabine in Combination With Placebo 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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
693

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

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

Study Locations

  • Germany
      • Darmstadt, Germany
        • Please Contact Merck Communication Center
  • United States
    • Massachusetts
      • Rockland, Massachusetts, United States
        • Please Contact U.S. Medical Information

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.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Study Plan

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

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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 subject withdrawal.
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Overall Survival
Time Frame: 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
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Progression Free Survival
Time Frame: 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
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

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
ImmunoGenesis

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Threshold Pharmaceuticals

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Antonio Gualberto, MD, PhD, EMD Serono Inc., a subsidiary of Merck KGaA, Darmstadt, Germany

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 Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 1, 2012

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 1, 2016

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 1, 2016

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 7, 2012

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 7, 2012

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 11, 2012

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 11, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 8, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • EMR 200592-001
  • 2012-002957-42 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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