Trivalent Ganglioside Vaccine With Immunological Adjuvant or Immunological Adjuvant Alone in Metastatic Sarcoma Patients Who Are Rendered Disease Free

March 14, 2017 updated by: MabVax Therapeutics, Inc.

A Randomized, Multicenter, Double-Blind, Phase II Trial of a KLH Conjugated Trivalent Ganglioside Vaccine Containing GM2, GD2 Lactone, and GD3 Lactone With the Immunological Adjuvant OPT-821 Versus OPT-821 Alone in Metastatic Sarcoma Patients Who Are Rendered Disease Free

Sarcoma patients are at high risk for their cancer to recur even when the sarcoma has been removed surgically or treated with radiation or chemotherapy. The patients in the study will be randomized (like flipping a coin) to receive either a vaccine that is combined with an immune system stimulant or the immune system stimulant alone. The immune system stimulant is called OPT-821 and is an immunological booster. The trivalent vaccine is being developed to teach the patient's immune system to recognize 3 types of sugars called GM2, GD2 and GD3 that are found primarily on the surface of sarcoma cells. If the trivalent vaccine can stimulate the patient's immune system to develop antibodies which recognize and target the GM2, GD2 and GM3 sugars, then the patient's antibodies could attack and kill any remaining sarcoma cells potentially preventing the recurrence of sarcoma.

Study Overview

Status

Completed

Conditions

Detailed Description

This study is a Phase II randomized, double-blind, multi-center study of a trivalent ganglioside vaccine plus the immunological adjuvant OPT-821 (Arm A) versus OPT-821 alone (Arm B) for patients with metastatic sarcoma at initial presentation or with relapsed disease who have been rendered disease-free following either surgical resection or multi-modality therapy. The primary aim of this study is to demonstrate the efficacy of vaccine therapy over non-specific immune therapy. Another aim of this study is to obtain sufficient data to further the development of this specific vaccine therapy as well as guide future study designs for therapeutic cancer vaccines in general.

To be eligible, patients must have histologically confirmed sarcoma, must be clinically free of disease after surgery or multimodality therapy, and must be within 8 weeks of completion of such therapy. Given the limited data regarding ganglioside expression in Ewing sarcoma, rhabdomyosarcoma, and gastrointestinal stromal tumors, patients with these sarcoma subtypes with the exception of pleomorphic/anaplastic rhabdomyosarcoma will be excluded. Patients must have a history of distant metastatic disease; patients with locally recurrent disease only will not be eligible, as these patients demonstrate a different natural history from those with metastatic disease.

All treatment will be performed in the outpatient setting. Patients will be randomized in a 1:1 ratio to receive a total of 10 treatments of either the vaccine plus OPT-821 (Arm A) or OPT-821 alone (Arm B). Treatment will be administered on Visit Weeks 1, 2, 3, 8, 16, 28, 40, 52, 68, and 84. All patients will receive 150 mcg of OPT-821.

Study Type

Interventional

Enrollment (Actual)

136

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • California
      • Los Angeles, California, United States, 90025
        • UCLA Medical Center
    • Colorado
      • Denver, Colorado, United States, 80045
        • University of Colorado (Denver)
    • Georgia
      • Atlanta, Georgia, United States, 30308
        • Winship Cancer Institute at Emory Midtown
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University - Robert H. Lurie Comprehensive Cancer Center
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • University of Iowa Hospitals and Clinic
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Dana Farber Cancer Institute
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan Hospital
    • Missouri
      • St. Louis, Missouri, United States, 63110
        • Washington University School of Medicine
    • New York
      • New York, New York, United States, 10065
        • Memorial Sloan-Kettering Cancer Center
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health & Sciences University
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15232
        • University of Pittsburg Hillman Cancer Center
    • Washington
      • Seattle, Washington, United States, 98109
        • Fred Hutchinson Cancer Research Center/Seattle Cancer Care

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Male or female, 16 years or older.
  2. American Joint Committee on Cancer (AJCC) Stage IV sarcoma with no current radiological evidence of residual disease following either surgery alone or multi-modality therapy for treatment of metastatic or relapsed disease. Patients must have presented with either newly diagnosed metastatic sarcoma or distant relapsed disease. Patients who present with more than one site of metastases are eligible as long as at least one new site is distant from the original site and the surgical resection(s) results in clear margins as assessed by the site pathologist. Non-surgical local ablative therapies such as SRS or cryotherapy cannot replace surgical resection of disease for the purpose of eligibility.
  3. Histological confirmation of sarcoma, as performed by a pathologist at one of the participating study sites, prior to entry on study.
  4. Patients must have undergone surgical metastectomy within 8 weeks prior to initiation of treatment on this study.
  5. Patients previously treated with neoadjuvant chemotherapy and/or radiotherapy as part of a multi-modality treatment for metastatic disease must have recovered from all adverse effects of treatment and have returned to baseline status.
  6. Imaging study performed within 4 weeks prior to administration of first vaccination documenting that patient has no evidence of disease. Study must include CT scan of chest, abdomen, and pelvis.
  7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1.
  8. Weight ≥ 40 kg.
  9. Have organ and marrow function as defined below:

    WBC ≥ 3.0 cells/mm3 Platelets ≥ 100,000/mm3 Total bilirubin ≤ 2.0 mg/dL AST (SGOT)/ALT (SGPT) ≤ 1.5 x ULN

  10. Current use of an acceptable form of birth control.
  11. Ability to understand English and to provide written informed consent and authorization for protected health information disclosure whether by self or by legally authorized representative.

Exclusion Criteria:

  1. Patients with evidence of local or metastatic disease or who are not disease free at the time of the first vaccination.
  2. Patients who develop locally recurrent disease only with no evidence of concurrent or previous distant metastatic disease. Patients with a primary retroperitoneal and/or uterine sarcoma that present with recurrence within the retroperitoneum or pelvis only are not eligible. Patients must have evidence of hematogenously disseminated distant disease.
  3. Patients with brain or bone metastasis even if they are able to undergo complete surgical resection.
  4. Patients with Ewing sarcoma, rhabdomyosarcoma (except for pleomorphic/anaplastic rhabdomyosarcoma), or gastrointestinal stromal tumors. Patients with pleomorphic/anaplastic rhabdomyosarcoma are eligible.
  5. Patients previously treated with KLH or ganglioside containing vaccines or monoclonal antibodies (mAbs) against gangliosides.
  6. Females of childbearing potential that are pregnant or intend to become pregnant or who are breastfeeding. Females must have negative βHCG test within two weeks of first vaccination.
  7. Current active malignancy or history of malignancy, other than sarcoma, within the past two years, except for cervical carcinoma in situ or superficial skin cancer that has been surgically removed.
  8. Any medical condition that may limit the ability of the patient to complete the full course of treatment or to respond immunologically to vaccination, (including autoimmune or neurodegenerative disorders such as multiple sclerosis and amyotrophic lateral sclerosis).
  9. Patients requiring continuous doses of anti-inflammatory medications (steroids including inhaled steroids, non-steroidal anti-inflammatory drugs, or full dose aspirin). Episodic use of steroids or non-steroidal anti-inflammatory drugs permitted as long as they are not given within one week prior to or following vaccine administration. Continuous dosing of low-dose aspirin (≤ 81 mg/day) is acceptable.
  10. Use of or treatment with a drug that has not received regulatory approval or participation in a drug or device study during the 28 days preceding the first vaccination.
  11. Known history of HIV-positivity OR serologic evidence of HIV at screening or any immunodeficiency disorders or illnesses. Serologic positivity for the Hepatitis B Virus (HBV) or the Hepatitis C Virus (HCV), unless explained by a documented vaccination.
  12. Inability or unwillingness to meet the attendance requirements of the study.
  13. Any clinically significant abnormal finding at Screening (as determined by the principal investigator, in consultation with the Medical Monitor and the Sponsor), that would interfere with study participation, that would interfere with the evaluation or quality of the data, or that would put the patient at increased risk of illness or injury.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm A
Vaccine plus OPT-821
Patients will be given 10 injections of ganglioside vaccine plus adjuvant OPT-821 as a 1.0 ml subcutaneous injection in an outpatient setting at Visit Weeks 1, 2, 3, 8, 16, 28, 40, 52, 68 and 84
Other Names:
  • Trivalent ganglioside vaccine plus adjuvant OPT-821
Active Comparator: Arm B - OPT-821 immunologic adjuvant
Patients will be given 10 injections of OPT-821 alone as a 1.0 ml subcutaneous injection in an outpatient setting at Visit Weeks 1, 2, 3, 8, 16, 28, 40, 52, 68 and 84
Patients will be given 10 injections of adjuvant OPT-821 as a 1.0 ml subcutaneous injection in an outpatient setting at Visit Weeks 1, 2, 3, 8, 16, 28, 40, 52, 68 and 84
Other Names:
  • Immunologic adjuvant OPT-821

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression Free Survival
Time Frame: 3-years

The primary objective is to compare the progression-free survival (PFS) over time.

Progression free survival is defined as the time from randomization until any evidence of tumor growth or appearance anywhere in the body or death from any cause as determined by the principal investigator at each site. The principal investigator will determine Progression-free survival by using CT scans to evaluate disease recurrence. For the purpose of this study, progression of disease is defined as the development of tumor growth or recurrence at any site of the body as determined by the principal investigator at each study site or death from disease

3-years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival
Time Frame: Measured over time
To compare the overall survival over time, to estimate the median and 3-year progression-free survival.
Measured over time

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: William Tap, M.D., Memorial Sloan Kettering Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2010

Primary Completion (Actual)

September 1, 2013

Study Completion (Actual)

March 10, 2017

Study Registration Dates

First Submitted

June 9, 2010

First Submitted That Met QC Criteria

June 9, 2010

First Posted (Estimate)

June 10, 2010

Study Record Updates

Last Update Posted (Actual)

April 12, 2017

Last Update Submitted That Met QC Criteria

March 14, 2017

Last Verified

December 1, 2016

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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