Clinical trial NCT01141491: Trivalent Ganglioside Vaccine With Immunological Adjuvant or Immunological Adjuvant Alone in Metastatic Sarcoma Patients Who Are Rendered Disease Free
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Sarcoma
Keywords: Sarcoma
Metastatic
Vaccine
Adjuvant
Lead sponsor: MabVax Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2010-06-10
Enrollment: 136
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Progression Free Survival
timeFrame: 3-years
Secondary outcomes:
measure: Overall Survival
timeFrame: Measured over time
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA Medical Center
state: California
city: Denver
country: United States
facility: University of Colorado (Denver)
state: Colorado
city: Atlanta
country: United States
facility: Winship Cancer Institute at Emory Midtown
state: Georgia
city: Chicago
country: United States
facility: Northwestern University - Robert H. Lurie Comprehensive Cancer Center
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinic
state: Iowa
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Hospital
state: Michigan
city: St. Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Sciences University
state: Oregon
city: Pittsburgh
country: United States
facility: University of Pittsburg Hillman Cancer Center
state: Pennsylvania
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center/Seattle Cancer Care
state: Washington
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: William Tap, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rosenbaum E, Chugh R, Ryan CW, Agulnik M, Milhem MM, George S, Jones RL, Chmielowski B, Van Tine BA, Tawbi H, Elias AD, Read WL, Budd GT, Qin LX, Rodler ET, Hirman J, Weiden P, Bennett CM, Livingston PO, Ragupathi G, Hansen D, D'Angelo SP, Tap WD, Schwartz GK, Maki RG, Carvajal RD. A randomised phase II trial of a trivalent ganglioside vaccine targeting GM2, GD2 and GD3 combined with immunological adjuvant OPT-821 versus OPT-821 alone in metastatic sarcoma patients rendered disease-free by surgery. Eur J Cancer. 2022 Nov;176:155-163. doi: 10.1016/j.ejca.2022.09.003. Epub 2022 Oct 8.
citation: Cheung IY, Cheung NV, Modak S, Mauguen A, Feng Y, Basu E, Roberts SS, Ragupathi G, Kushner BH. Survival Impact of Anti-GD2 Antibody Response in a Phase II Ganglioside Vaccine Trial Among Patients With High-Risk Neuroblastoma With Prior Disease Progression. J Clin Oncol. 2021 Jan 20;39(3):215-226. doi: 10.1200/JCO.20.01892. Epub 2020 Dec 16.