A Phase 3, Randomized, Double-blind, Placebo-controlled Study For Subjects With Locally-advanced Unresectable or Metastatic Synovial Sarcoma (V943-003, IMDZ-04-1702)

Cancer Clinical Trial

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03520959
• Other study ID #: IMDZ-04-1702
• Secondary ID: V943A-003
• Status: Terminated
• Phase: Phase 3
• Start date: September 18, 2018
• Est. completion date: November 20, 2018

Study information

• Verified date: April 2020
• Source: Immune Design
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: November 20, 2018
• Est. primary completion date: November 20, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cancer
• Metastatic Sarcoma
• Sarcoma
• Sarcoma, Synovial
• Soft Tissue Sarcoma
• Synovial Sarcoma

Intervention

Biological:
• LV305
Administered via subcutaneous (SC) injection.
• G305
Administered via intramuscular (IM) injection.

Other:
• LV305-matching placebo
Administered via SC injection.
• G305-matching placebo
Administered via IM injection.

Locations

Country	Name	City	State
Canada	University of Alberta Hospital- Cross Cancer Institute	Edmonton
Canada	McGill University	Montréal-Est
United States	University of Michigan	Ann Arbor	Michigan
United States	Cohen Children's Medical Center (Northwell)	Astoria	New York
United States	Dana Farber Cancer Institute/Mass General Hospital	Boston	Massachusetts
United States	University of Colorado Cancer Center	Boulder	Colorado
United States	Northwestern	Chicago	Illinois
United States	Cincinnati Children's Hospital	Cincinnati	Ohio
United States	Ohio State University	Columbus	Ohio
United States	University of Miami	Coral Gables	Florida
United States	Duke University	Durham	North Carolina
United States	Hackensack University Medical Center	Edison	New Jersey
United States	MD Anderson Cancer Center	Houston	Texas
United States	Mayo Clinic- Jacksonville	Jacksonville	Florida
United States	USC Norris Comprehensive Cancer Center	Los Angeles	California
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Yale University School of Medicine- Cancer Center	New Haven	Connecticut
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Nebraska Methodist Hospital	Omaha	Nebraska
United States	Stanford University	Palo Alto	California
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Oregon Health and Science University	Portland	Oregon
United States	Washington University in St. Louis	Saint Louis	Missouri
United States	Sarcoma Oncology Center	Santa Monica	California
United States	Mayo Clinic- Scottsdale	Scottsdale	Arizona
United States	Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance	Seattle	Washington
United States	Moffitt Cancer Center at USF	Tampa	Florida
United States	University of Arizona Cancer Center	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Immune Design

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	From randomization to investigator-determined date of disease progression or death, assessed up to 24 months.
Primary	Overall Survival (OS)	OS is defined as the time from randomization to the date of death.	From randomization to date of death, assessed up to 66 months.
Secondary	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.	From last dose of CMB305 to initiation of new therapy, assessed up to 24 months.
Secondary	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.	From randomization to investigator-determined date of disease progression or death, assessed up to 24 months.
Secondary	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.	From randomization to investigator-determined date of disease progression, assessed up to 24 months.
Secondary	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.	From randomization to investigator-determined date of disease progression or death, assessed up to approximately 2 months.
Secondary	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).	From Day 1 up to 12 months
Secondary	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.	Up to approximately 2 months