Sarcoma Study of MORAb-004 Utilization: Research and Clinical Evaluation (SOURCE)

A Study of the Safety and Efficacy of the Combination of Gemcitabine and Docetaxel With MORAb-004 in Metastatic Soft Tissue Sarcoma

This study is being done to see if MORAb-004 increases the effectiveness of the chemotherapies gemcitabine and docetaxel in people with metastatic Soft Tissue Sarcoma.

Study Overview

• Status: Completed
• Conditions: Metastatic Soft Tissue Sarcoma
• Intervention / Treatment: Drug: Placebo; Drug: MORAb-004; Drug: Gemcitabine; Drug: Docetaxel

• Study Type: Interventional
• Enrollment (Actual): 209
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Australian Capital Territory
    • Garran, Australian Capital Territory, Australia, 2605
      • Canberra Hospital
  • New South Wales
    • St. Leonards, New South Wales, Australia, 2065
      • Royal North Shore Hospital
  • Queensland
    • Woolloongabba, Queensland, Australia, 4102
      • Princess Alexandra Hospital
  • South Australia
    • Kurralta Park, South Australia, Australia, 5037
      • Ashford Cancer Centre Research
  • Western Australia
    • Perth, Western Australia, Australia, 6009
      • Sir Charles Gairdner Hospital
• Belgium
  • Leuven, Belgium, 3000
    • UZ Leuven Medical Oncology
• France
  • Villejuif, France, 94805
    • Institut Gustave Roussy
  • Villeurbanne, France, 69100
    • University of Claude Bernard
• Italy
  • Bologna, Italy, 40136
    • Istituto Ortopedico Rizzoli
• Netherlands
  • Leiden, Netherlands
    • Leiden University Medical Center
• United States
  • California
    • Santa Monica, California, United States, 90403
      • Sarcoma Oncology Center
    • Santa Monica, California, United States, 90404
      • UCLA
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Jacksonville
    • Miami, Florida, United States, 33136
      • University of Miami
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Memorial Hospital
  • Iowa
    • Sioux City, Iowa, United States, 51101
      • Siouxland Hematology-Oncology
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Sidney Kimmel Comprehensive Cancer Center at John Hopkins
  • Massachusetts
    • Boston, Massachusetts, United States, 2215
      • Dana-Farber Cancer Institute
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Health System
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai Medical Center
    • Rochester, New York, United States, 55905
      • Mayo Clinic - Rochester
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • The University of North Carolina at Chapel Hill
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute at the University of Utah
  • Washington
    • Seattle, Washington, United States
      • Seattle Care Alliance

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Be at least 18 years of age
• Be surgically sterile or consent to use a medically acceptable method of contraception throughout the study period
• Have a histologically confirmed diagnosis of mSTS as defined by the 4 specified study subgrouped
• Have been treated in the metastatic setting with 0 to 2 prior systemic regimens for mSTS (Systemic treatment regimens given in the neoadjuvant setting and maintenance therapies will not be considered as regimens in the metastatic setting for the purposes of this protocol. Prior anthracycline-based regimen is allowable but not required. Subjects with extra-skeletal small round blue cell sarcomas, including rhabdomyosarcomas, must have exhausted or be intolerant of standard first line anthracycline-based chemotherapy.)
• Have measurable disease, as defined by RECIST v 1.1 assess within 2 weeks of study entry and have radiologically documented disease progression greater than or equal to a 10% increase in the sum of the longest diameters of target lesions present within 6 months prior to randomization
• Have tumor tissue available for TEM-1 biomarker studies
• Be willing and able to provide written informed consent

Exclusion Criteria:

• Have received more than 2 prior systemic treatment regimens for mSTS
• Have received either gemcitabine or docetaxel in any previous treatment for mSTS (regardless of the line of treatment)
• Have a diagnosis of primary bone sarcoma of any histological type.
• Have a history of clinically significant heart disease, or clinically significant arrhythmia on ECG within the past 6 months
• Have a history of allergic reaction to prior monoclonal antibody or biologic agent
• Have received previous treatment with MORAb-004 (anti-TEM-1)
• Have a medical condition with a high risk of bleeding (e.g., a known bleeding disorder, a coagulopathy, or a tumor that involves the major vessels) or have a recent (within past 6 months) history of a significant bleeding event
• Have undergone major surgical procedures or open biopsy, have significant traumatic injury within 30 days prior to the first date of study treatment, or have major surgical procedures anticipated during the study
• Have a serious non-healing wound, an ulcer (including gastrointestinal), or a bone fracture

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MORAb-004, gemcitabine, docetaxel	Drug: MORAb-004; IV, Days 1 and 8 of every cycle until disease progression; Drug: Gemcitabine; IV, Days 1 and 8 of each cycle until disease progression; Drug: Docetaxel; IV, Day 8 of every cycle until disease progression
Active Comparator: Placebo, gemcitabine, docetaxel	Drug: Placebo; Drug: Gemcitabine; IV, Days 1 and 8 of each cycle until disease progression; Drug: Docetaxel; IV, Day 8 of every cycle until disease progression

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 2: Radiologic Progression-free Survival (PFS)	PFS was defined as the time (in weeks) from the date of randomization to the date of first observation of disease progression according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) or date of death, regardless of the cause.	From date of first dose until date of first observation of disease progression, or death due to any cause (up to approximately 3 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 2: Symptomatic Progression-free Survival	PFS including symptomatic progression was defined as the time (in weeks) from the date of randomization to the date of the first observation of disease progression according to RECIST 1.1, symptomatic progression, or death due to any cause.	From date of first dose until date of first observation of disease progression, symptomatic progression, or death due to any cause (up to approximately 3 years)
Part 2: Overall Survival (OS)	OS was defined as the time (in months) from the date of randomization to the date of death, regardless of the cause.	From date of first dose until date of death from any cause (up to approximately 3.5 years)
Part 2: Overall Response Rate (ORR)	ORR was defined as the percentage of subjects with either a complete response (CR) or a partial response (PR) based on RECIST 1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<) 10 millimeter (mm). PR was defined as at least a 30 percent (%) decrease in sum of diameters of target lesions, taking as reference the baseline sum of diameters.	From date of first dose until disease progression (up to approximately 3.5 years)
Part 2: Radiologic Progression-free Survival Rate (PFR)	Radiologic progression-free survival rate was defined as the percentage of subjects achieving radiologic PFS at the pre-specified time points.	Weeks 12, 24, 48 and 52
Part 2: Number of Participants Who Had Relationship Between MORAb-004 Exposures and Biomarker Levels		Up to approximately 3 years

Collaborators and Investigators

• Sponsor: Morphotek

Publications and helpful links

General Publications

• Jones RL, Chawla SP, Attia S, Schoffski P, Gelderblom H, Chmielowski B, Le Cesne A, Van Tine BA, Trent JC, Patel S, Wagner AJ, Chugh R, Heyburn JW, Weil SC, Wang W, Viele K, Maki RG. A phase 1 and randomized controlled phase 2 trial of the safety and efficacy of the combination of gemcitabine and docetaxel with ontuxizumab (MORAb-004) in metastatic soft-tissue sarcomas. Cancer. 2019 Jul 15;125(14):2445-2454. doi: 10.1002/cncr.32084. Epub 2019 Apr 29.

Study record dates

Study Major Dates

• Study Start (Actual): August 7, 2012
• Primary Completion (Actual): August 11, 2015
• Study Completion (Actual): August 2, 2016

Study Registration Dates

• First Submitted: April 4, 2012
• First Submitted That Met QC Criteria: April 9, 2012
• First Posted (Estimate): April 10, 2012

Study Record Updates

• Last Update Posted (Actual): August 21, 2019
• Last Update Submitted That Met QC Criteria: August 1, 2019
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Gemcitabine; Docetaxel
• Other Study ID Numbers: MORAb-004-203-STS; 2012-001399-12 (EudraCT Number)