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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by EMD Serono
Sponsor:
Collaborator:
Threshold Pharmaceuticals
Information provided by (Responsible Party):
EMD Serono
ClinicalTrials.gov Identifier:
NCT01746979
First received: December 7, 2012
Last updated: September 8, 2014
Last verified: September 2014
  Purpose

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.


Condition Intervention Phase
Metastatic or Locally Advanced Unresectable Pancreatic Adenocarcinoma
Drug: TH-302
Drug: Gemcitabine
Drug: Placebo (5 percent dextrose - D5W)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by EMD Serono:

Primary Outcome Measures:
  • Overall Survival Time [ Time Frame: Anticipated up to 4 years ] [ Designated as safety issue: No ]
    Overall survival time is defined as time from randomization to death or last day known to be alive.


Secondary Outcome Measures:
  • Progression Free Survival Time [ Time Frame: Anticipated up to 4 years ] [ Designated as safety issue: No ]
    Progression Free Survival time is defined as the time from randomization to either first observation of progressive disease or occurrence of death.

  • Percentage of subjects with best overall response according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v.1.1) [ Time Frame: Anticipated up to 4 years ] [ Designated as safety issue: No ]
    Percentage of subjects with objective response is based on assessment of complete response (CR) or partial response (PR) according to RECIST v.1.1.

  • Percentage of subjects with disease control according to RECIST v.1.1 [ Time Frame: Anticipated up to 4 years ] [ Designated as safety issue: No ]
    Percentage of subjects with disease control is based on assessment of complete response (CR) or partial response (PR) or stable disease (SD) according to RECIST v.1.1.

  • Quality of Life (QOL) EuroQuol-5D (EQ-5D) Health Outcome questionnaire [ Time Frame: Anticipated up to 4 years ] [ Designated as safety issue: No ]
    The EuroQuol-5D (EQ-5D) questionnaire is a measure of health status that provides a simple descriptive profile and a single index value. The EQ-5D defines health in terms of mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The 5 items are combined to generate health profiles. These profiles are converted to a continuous single index score using a one to one matching. The lowest possible score is -0.59 and the highest is 1.00, wherein higher scores on the EQ-5D represent a better QOL.

  • Quality of Life (QOL) Assessment European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) (Version 3.0) [ Time Frame: Anticipated up to 4 years ] [ Designated as safety issue: No ]
    The EORTC QLQ-C30 scores were derived from mutually exclusive sets of items, with scale scores ranging from 0 to 100 after a linear transformation. Higher scores indicate a higher level of functioning.

  • Pain intensity using a Numerical Rating Scale (NRS) [ Time Frame: Anticipated up to 4 years ] [ Designated as safety issue: No ]
    The 11-point NRS will be used to assess pain intensity. The score can vary between "0" and "10" wherein, 0 = no pain and 10 = the worst possible pain.

  • Serum Carcinoma Antigen 19-9 response rate [ Time Frame: Anticipated up to 4 years ] [ Designated as safety issue: No ]
    Serum Carcinoma antigen 19-9 is a serum marker for pancreatic cancer.

  • Number of subjects with treatment-emergent adverse events (TEAEs) according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v.4.03) [ Time Frame: Anticipated up to 4 years ] [ Designated as safety issue: Yes ]
    An Adverse Event (AE) is defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. Treatment-emergent adverse events are events from first dose of study drug that were absent before treatment or that worsened relative to pretreatment state.


Estimated Enrollment: 660
Study Start Date: December 2012
Estimated Study Completion Date: February 2017
Estimated Primary Completion Date: February 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01746979

Locations
United States, Massachusetts
Please Contact U.S. Medical Information Located in Recruiting
Rockland, Massachusetts, United States
Contact: for US Recruiting Sites    888-275-7376      
Germany
Please Contact Merck Communication Services Located in Recruiting
Darmstadt, Germany
Contact: for EU Recruiting Sites    +49 6151 72 5200    service@merckgroup.com   
Sponsors and Collaborators
EMD Serono
Threshold Pharmaceuticals
Investigators
Study Director: Antonio Gualberto, MD, PhD EMD Serono Inc., a subsidiary of Merck KGaA, Darmstadt, Germany
  More Information

Additional Information:
No publications provided

Responsible Party: EMD Serono
ClinicalTrials.gov Identifier: NCT01746979     History of Changes
Other Study ID Numbers: EMR 200592-001, 2012-002957-42
Study First Received: December 7, 2012
Last Updated: September 8, 2014
Health Authority: United States: Food and Drug Administration
European Union: European Medicines Agency
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Australia: Department of Health and Ageing Therapeutic Goods Administration
Canada: Health Canada
Brazil: National Health Surveillance Agency
Israel: Ministry of Health
Japan: Pharmaceuticals and Medical Devices Agency
South Korea: Ministry of Food and Drug Safety
Russia: Ministry of Health of the Russian Federation

Keywords provided by EMD Serono:
TH-302; Pancreatic Cancer; EMR200592-001

Additional relevant MeSH terms:
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Gemcitabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on September 16, 2014