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

Study Overview
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Brief Summary
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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.

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

Conditions
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Metastatic Soft Tissue Sarcoma

Intervention / Treatment
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* Drug: MORAb-004
* Drug: Gemcitabine
* Drug: Docetaxel
* Drug: Gemcitabine
* Drug: Docetaxel
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 |