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

Primary Purpose

Metastatic or Locally Advanced Unresectable Pancreatic Adenocarcinoma

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

TH-302

Gemcitabine

Placebo (5 percent dextrose - D5W)

About this trial

This is an interventional treatment trial for Metastatic or Locally Advanced Unresectable Pancreatic Adenocarcinoma focused on measuring TH-302, Evofosfamide, Pancreatic Cancer, EMR200592-001

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Please Contact U.S. Medical Information
Please Contact Merck Communication Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Gemcitabine plus TH-302

Gemcitabine plus placebo

Arm Description

Outcomes

Primary Outcome Measures

Overall Survival

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

Secondary Outcome Measures

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.

Full Information

NCT ID

NCT01746979

First Posted

December 7, 2012

Last Updated

October 26, 2017

Sponsor

Threshold Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT01746979

Brief Title

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

Acronym

MAESTRO

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2017

Overall Recruitment Status

Completed

Study Start Date

December 2012 (undefined)

Primary Completion Date

February 2016 (Actual)

Study Completion Date

May 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Threshold Pharmaceuticals

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Metastatic or Locally Advanced Unresectable Pancreatic Adenocarcinoma

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

693 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Gemcitabine plus TH-302

Arm Type

Active Comparator

Arm Title

Gemcitabine plus placebo

Arm Type

Placebo Comparator

Intervention Type

Drug

Intervention Name(s)

TH-302

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Gemcitabine

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Placebo (5 percent dextrose - D5W)

Intervention Description

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 Measure Information:

Title

Overall Survival

Description

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

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

Secondary Outcome Measure Information:

Title

Progression Free Survival

Description

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Antonio Gualberto, MD, PhD

Organizational Affiliation

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

Official's Role

Study Director

Facility Information:

Facility Name

Please Contact U.S. Medical Information

City

Rockland

State/Province

Massachusetts

Country

United States

Facility Name

Please Contact Merck Communication Center

City

Darmstadt

Country

Germany

12. IPD Sharing Statement

Learn more about this trial

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

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