Back to resultsA Phase 3, Randomized, Double-blind, Placebo-controlled Study For Subjects With Locally-advanced Unresectable or Metastatic Synovial Sarcoma (V943-003, IMDZ-04-1702)
Primary Purpose
Synovial Sarcoma, Cancer, Soft Tissue Sarcoma
Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
LV305
G305
LV305-matching placebo
G305-matching placebo
Sponsored by
About this trial
This is an interventional treatment trial for Synovial Sarcoma focused on measuring Synovate Study, NY-ESO-1, cancer vaccine, Sarcoma, soft tissue sarcoma, immunotherapy
Eligibility Criteria
Selected Inclusion Criteria:
- Histological diagnosis of synovial sarcoma
- Immunohistochemistry (IHC) results from tumor biopsy for New York esophageal squamous cell carcinoma 1 (NY-ESO-1) are positive
- Participants have received at least 4 but no more than 8 cycles of first-line anthracycline or ifosfamide-containing systemic anti-cancer therapy regimen
- Must have documentation of no evidence of disease progression of the tumor during or after completion of first line systemic anti-cancer therapy
- ECOG (Eastern Cooperative Oncology Group) performance status of 0 or 1
- Age >/= 12 years
- Life expectancy of at least 6 months
Selected Exclusion Criteria:
- Have received last dose of first-line systemic anti-cancer therapy or date of most recent local regional therapy >28 days prior to day 1
- Have received prior anti-NY-ESO-1 therapy
- Have received first-line systemic anti-cancer therapy with an agent other than anthracycline or ifosfamide
- Have received treatment with systemic immunomodulatory agents within 28 days prior to administration of the first dose of CMB305, or 5 half-lives of the drug, whichever occurs sooner.
- Have significant immunosuppression from concurrent, recent, or anticipated need for chronic treatment with systemic immunosuppressive dose of corticosteroids or immunosuppressive medications.
- Have psychiatric or other medical illness, or any other condition that in the opinion of the investigator prevents compliance with the study procedures or ability to provide valid informed consent.
- Have history of uncontrolled autoimmune disease.
- Have a significant electrocardiogram finding or cardiovascular disease
- have inadequate organ function per protocol
- History of other cancer within 3 years
- Evidence of active tuberculosis or recent clinically-significant infection requiring systemic therapy.
- Evidence of active Hepatitis B, Hepatitis C, or Human Immunodeficiency virus (HIV) infection
- Have a history of brain metastasis
- Have received cancer therapies including chemotherapy, radiation, biologic, or kinase inhibitors, granulocyte-colony stimulating factor (G-CSF), or granulocyte-macrophage colony-stimulating factor (GM-CSF) within 3 weeks prior ot the first scheduled dose of CMB305
- Female of child bearing potential who is pregnant, is planning to become pregnant, or is breast feeding; or male who is sexually active with a female of child bearing potential who is planning to become pregnant.
Sites / Locations
- Mayo Clinic- Scottsdale
- University of Arizona Cancer Center
- USC Norris Comprehensive Cancer Center
- Stanford University
- Sarcoma Oncology Center
- University of Colorado Cancer Center
- Yale University School of Medicine- Cancer Center
- University of Miami
- Mayo Clinic- Jacksonville
- Moffitt Cancer Center at USF
- Northwestern
- Dana Farber Cancer Institute/Mass General Hospital
- University of Michigan
- Washington University in St. Louis
- Nebraska Methodist Hospital
- Hackensack University Medical Center
- Cohen Children's Medical Center (Northwell)
- Memorial Sloan Kettering Cancer Center
- Duke University
- Cincinnati Children's Hospital
- Ohio State University
- Oregon Health and Science University
- Fox Chase Cancer Center
- University of Pittsburgh Medical Center
- Vanderbilt University Medical Center
- MD Anderson Cancer Center
- Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance
- University of Alberta Hospital- Cross Cancer Institute
- McGill University
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Experimental
Arm Label
Placebo
CMB305
Arm Description
A sequential regimen of LV305-matching placebo and G305-matching placebo.
A sequential regimen of LV305 and G305.
Outcomes
Primary Outcome Measures
Progression-Free Survival (PFS)
PFS is defined as the time from randomization to the investigator-determined date of disease progression or death, whichever comes first, using Response Evaluation Criteria in Solid Tumors (RECIST v1.1).
Overall Survival (OS)
OS is defined as the time from randomization to the date of death.
Secondary Outcome Measures
Time to Next Treatment (TTNT)
TTNT is defined as the time from randomization to the start of post-study treatment subsequent intervention: [TTNT = start date of subsequent intervention - randomization date + 1]. Subsequent intervention includes anticancer therapy, cancer-related surgery and local regional therapy. Participants who do not start any post-study treatment intervention will be censored at their last known date of being alive.
Distant Metastasis Free Survival (DMFS)
DMFS is defined as the time from randomization to evidence of a new distant metastasis not documented at time of randomization: [DMFS = a new distant metastasis documented date - randomization date + 1]. Participants who do not have any new distant metastasis will be censored at their last tumor assessment.
Overall Response Rate (ORR)
ORR defined by RECIST v1.1 will be summarized by the number and percent of subjects who achieve a complete response (CR) or partial response (PR) based on the investigator's assessment. ORR will be compared between treatment arms using a logistic regression.
Number of Participants Who Experienced a Treatment-Emergent Adverse Event (TEAE)
Safety will be assessed primarily based on reported adverse events (AEs), Medical Events of Interest (MEOIs), laboratory values, and concomitant medications reported from initiation of treatment with CMB305 or placebo.
Quality of Life (QoL): EuroQol 5-Dimension 5 Level (EQ-5D-5L) and EuroQol 5-Dimension Youth (EQ-5D-Y) Questionnaires
QoL evaluated using the EQ-5D-5L for participants ≥18 years of age or using the EQ-5D-Y for participants 12 to <18 years of age. EQ-5D-5L descriptive system is comprised of 5 dimensions-mobility, self-care, usual activities, pain/discomfort & anxiety/depression. Each dimension has 5 levels: not at all (level 1), mild (level 2), moderate (level 3), severe (level 4), extreme/leading to incapacity (level 5), with highest level corresponding to worst outcome. Participants indicated their health state by choosing the appropriate level from each dimension. The 5 digit health states thus obtained for each dimension were then converted into a single median index value using the EQ-5D-5L crosswalk index value calculator as recommended by EuroQol group. In the EQ-VAS, participants recorded their health state on a scale ranging from 0 (worst imaginable health state) to 100 (best imaginable health state).
Number of Participants Who Discontinued Study Treatment Due to an AE
The number of all participants who discontinued study treatment due to an AE is presented.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03520959
Brief Title
A Phase 3, Randomized, Double-blind, Placebo-controlled Study For Subjects With Locally-advanced Unresectable or Metastatic Synovial Sarcoma (V943-003, IMDZ-04-1702)
Official Title
A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Determine the Efficacy and Safety of CMB305 in Unresectable Locally-advanced or Metastatic NY-ESO-1+ Synovial Sarcoma Participants Following First Line Systemic Anti-cancer Therapy (V943-003, IMDZ-04-1702)
Study Type
Interventional
2. Study Status
Record Verification Date
April 2020
Overall Recruitment Status
Terminated
Why Stopped
Study was terminated due to sponsor's decision.
Study Start Date
September 18, 2018 (Actual)
Primary Completion Date
November 20, 2018 (Actual)
Study Completion Date
November 20, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Immune Design
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
To assess if the CMB305 vaccine regimen may help the body's immune system to slow or stop the growth of synovial sarcoma tumor and improve survival.
Detailed Description
The Synovate Study is a global, randomized, double-blind, placebo-controlled, phase 3 study in patients with unresectable, locally-advanced or metastatic New York esophageal squamous cell carcinoma 1 (NY-ESO-1) positive synovial sarcoma following first-line systemic anti-cancer therapy.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Synovial Sarcoma, Cancer, Soft Tissue Sarcoma, Sarcoma, Metastatic Sarcoma
Keywords
Synovate Study, NY-ESO-1, cancer vaccine, Sarcoma, soft tissue sarcoma, immunotherapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
1 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
A sequential regimen of LV305-matching placebo and G305-matching placebo.
Arm Title
CMB305
Arm Type
Experimental
Arm Description
A sequential regimen of LV305 and G305.
Intervention Type
Biological
Intervention Name(s)
LV305
Intervention Description
Administered via subcutaneous (SC) injection.
Intervention Type
Biological
Intervention Name(s)
G305
Intervention Description
Administered via intramuscular (IM) injection.
Intervention Type
Other
Intervention Name(s)
LV305-matching placebo
Intervention Description
Administered via SC injection.
Intervention Type
Other
Intervention Name(s)
G305-matching placebo
Intervention Description
Administered via IM injection.
Primary Outcome Measure Information:
Title
Progression-Free Survival (PFS)
Description
PFS is defined as the time from randomization to the investigator-determined date of disease progression or death, whichever comes first, using Response Evaluation Criteria in Solid Tumors (RECIST v1.1).
Time Frame
From randomization to investigator-determined date of disease progression or death, assessed up to 24 months.
Title
Overall Survival (OS)
Description
OS is defined as the time from randomization to the date of death.
Time Frame
From randomization to date of death, assessed up to 66 months.
Secondary Outcome Measure Information:
Title
Time to Next Treatment (TTNT)
Description
TTNT is defined as the time from randomization to the start of post-study treatment subsequent intervention: [TTNT = start date of subsequent intervention - randomization date + 1]. Subsequent intervention includes anticancer therapy, cancer-related surgery and local regional therapy. Participants who do not start any post-study treatment intervention will be censored at their last known date of being alive.
Time Frame
From last dose of CMB305 to initiation of new therapy, assessed up to 24 months.
Title
Distant Metastasis Free Survival (DMFS)
Description
DMFS is defined as the time from randomization to evidence of a new distant metastasis not documented at time of randomization: [DMFS = a new distant metastasis documented date - randomization date + 1]. Participants who do not have any new distant metastasis will be censored at their last tumor assessment.
Time Frame
From randomization to investigator-determined date of disease progression or death, assessed up to 24 months.
Title
Overall Response Rate (ORR)
Description
ORR defined by RECIST v1.1 will be summarized by the number and percent of subjects who achieve a complete response (CR) or partial response (PR) based on the investigator's assessment. ORR will be compared between treatment arms using a logistic regression.
Time Frame
From randomization to investigator-determined date of disease progression, assessed up to 24 months.
Title
Number of Participants Who Experienced a Treatment-Emergent Adverse Event (TEAE)
Description
Safety will be assessed primarily based on reported adverse events (AEs), Medical Events of Interest (MEOIs), laboratory values, and concomitant medications reported from initiation of treatment with CMB305 or placebo.
Time Frame
From randomization to investigator-determined date of disease progression or death, assessed up to approximately 2 months.
Title
Quality of Life (QoL): EuroQol 5-Dimension 5 Level (EQ-5D-5L) and EuroQol 5-Dimension Youth (EQ-5D-Y) Questionnaires
Description
QoL evaluated using the EQ-5D-5L for participants ≥18 years of age or using the EQ-5D-Y for participants 12 to <18 years of age. EQ-5D-5L descriptive system is comprised of 5 dimensions-mobility, self-care, usual activities, pain/discomfort & anxiety/depression. Each dimension has 5 levels: not at all (level 1), mild (level 2), moderate (level 3), severe (level 4), extreme/leading to incapacity (level 5), with highest level corresponding to worst outcome. Participants indicated their health state by choosing the appropriate level from each dimension. The 5 digit health states thus obtained for each dimension were then converted into a single median index value using the EQ-5D-5L crosswalk index value calculator as recommended by EuroQol group. In the EQ-VAS, participants recorded their health state on a scale ranging from 0 (worst imaginable health state) to 100 (best imaginable health state).
Time Frame
From Day 1 up to 12 months
Title
Number of Participants Who Discontinued Study Treatment Due to an AE
Description
The number of all participants who discontinued study treatment due to an AE is presented.
Time Frame
Up to approximately 2 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Selected Inclusion Criteria:
Histological diagnosis of synovial sarcoma
Immunohistochemistry (IHC) results from tumor biopsy for New York esophageal squamous cell carcinoma 1 (NY-ESO-1) are positive
Participants have received at least 4 but no more than 8 cycles of first-line anthracycline or ifosfamide-containing systemic anti-cancer therapy regimen
Must have documentation of no evidence of disease progression of the tumor during or after completion of first line systemic anti-cancer therapy
ECOG (Eastern Cooperative Oncology Group) performance status of 0 or 1
Age >/= 12 years
Life expectancy of at least 6 months
Selected Exclusion Criteria:
Have received last dose of first-line systemic anti-cancer therapy or date of most recent local regional therapy >28 days prior to day 1
Have received prior anti-NY-ESO-1 therapy
Have received first-line systemic anti-cancer therapy with an agent other than anthracycline or ifosfamide
Have received treatment with systemic immunomodulatory agents within 28 days prior to administration of the first dose of CMB305, or 5 half-lives of the drug, whichever occurs sooner.
Have significant immunosuppression from concurrent, recent, or anticipated need for chronic treatment with systemic immunosuppressive dose of corticosteroids or immunosuppressive medications.
Have psychiatric or other medical illness, or any other condition that in the opinion of the investigator prevents compliance with the study procedures or ability to provide valid informed consent.
Have history of uncontrolled autoimmune disease.
Have a significant electrocardiogram finding or cardiovascular disease
have inadequate organ function per protocol
History of other cancer within 3 years
Evidence of active tuberculosis or recent clinically-significant infection requiring systemic therapy.
Evidence of active Hepatitis B, Hepatitis C, or Human Immunodeficiency virus (HIV) infection
Have a history of brain metastasis
Have received cancer therapies including chemotherapy, radiation, biologic, or kinase inhibitors, granulocyte-colony stimulating factor (G-CSF), or granulocyte-macrophage colony-stimulating factor (GM-CSF) within 3 weeks prior ot the first scheduled dose of CMB305
Female of child bearing potential who is pregnant, is planning to become pregnant, or is breast feeding; or male who is sexually active with a female of child bearing potential who is planning to become pregnant.
Facility Information:
Facility Name
Mayo Clinic- Scottsdale
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85259
Country
United States
Facility Name
University of Arizona Cancer Center
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85724
Country
United States
Facility Name
USC Norris Comprehensive Cancer Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
Stanford University
City
Palo Alto
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
Sarcoma Oncology Center
City
Santa Monica
State/Province
California
ZIP/Postal Code
90403
Country
United States
Facility Name
University of Colorado Cancer Center
City
Boulder
State/Province
Colorado
ZIP/Postal Code
80309
Country
United States
Facility Name
Yale University School of Medicine- Cancer Center
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520
Country
United States
Facility Name
University of Miami
City
Coral Gables
State/Province
Florida
ZIP/Postal Code
33146
Country
United States
Facility Name
Mayo Clinic- Jacksonville
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
Facility Name
Moffitt Cancer Center at USF
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Northwestern
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Dana Farber Cancer Institute/Mass General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Washington University in St. Louis
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Nebraska Methodist Hospital
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68114
Country
United States
Facility Name
Hackensack University Medical Center
City
Edison
State/Province
New Jersey
ZIP/Postal Code
08837
Country
United States
Facility Name
Cohen Children's Medical Center (Northwell)
City
Astoria
State/Province
New York
ZIP/Postal Code
11105
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Duke University
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27708
Country
United States
Facility Name
Cincinnati Children's Hospital
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Facility Name
Ohio State University
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Oregon Health and Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Fox Chase Cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19111
Country
United States
Facility Name
University of Pittsburgh Medical Center
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15224
Country
United States
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Facility Name
University of Alberta Hospital- Cross Cancer Institute
City
Edmonton
Country
Canada
Facility Name
McGill University
City
Montréal-Est
Country
Canada
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Phase 3, Randomized, Double-blind, Placebo-controlled Study For Subjects With Locally-advanced Unresectable or Metastatic Synovial Sarcoma (V943-003, IMDZ-04-1702)
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