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

• Sponsor: MabVax Therapeutics, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01141491
• Collaborator: (none)
• Enrollment: 136
• Locations: 13
• Arms: 2
• Duration (Months): 81.3
• Patients Per Site: 10.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Sarcoma	Biological: Trivalent ganglioside vaccine; Biological: OPT-821	Phase 2

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

1. 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 Design

• Study Type: Interventional
• Actual Enrollment: 136 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• 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 Start Date: Jun 1, 2010
• Actual Primary Completion Date: Sep 1, 2013
• Actual Study Completion Date: Mar 10, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A Vaccine plus OPT-821	Biological: Trivalent ganglioside vaccine; 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	Biological: OPT-821; 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

Outcome Measures

Primary Outcome Measures

1. Progression Free Survival [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

Secondary Outcome Measures

1. Overall Survival [Measured over time]

   To compare the overall survival over time, to estimate the median and 3-year progression-free survival.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 16 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

1. Current use of an acceptable form of birth control.

2. 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.

Contacts and Locations

Locations

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

Sponsors and Collaborators

• MabVax Therapeutics, Inc.

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• NCI sarcoma information
• Related Info

Publications

None provided.

• Responsible Party: MabVax Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT01141491
• Other Study ID Numbers: MV-0109DP001
• First Posted: Jun 10, 2010
• Last Update Posted: Apr 12, 2017
• Last Verified: Dec 1, 2016

• Keywords provided by MabVax Therapeutics, Inc.: Sarcoma; Metastatic; Vaccine; Adjuvant
• Additional relevant MeSH terms: Sarcoma; Vaccines; Adjuvants, Immunologic

Study Results

Participant Flow

Arm/Group Title	Arm A- Vaccine Plus OPT-821	Arm B - OPT-821 Immunologic Adjuvant
Arm/Group Description	Trivalent ganglioside vaccine: 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	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
Period Title: Overall Study
STARTED	68	68
COMPLETED	20	21
NOT COMPLETED	48	47

Baseline Characteristics

Arm/Group Title	Arm A- Vaccine Plus OPT-821	Arm B - OPT-821 Immunologic Adjuvant	Total
Arm/Group Description	Trivalent ganglioside vaccine: 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	OPT-821: 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	Total of all reporting groups
Overall Participants	68	68	136
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	57 83.8%	51 75%	108 79.4%
>=65 years	11 16.2%	17 25%	28 20.6%
Sex: Female, Male (Count of Participants)
Female	29 42.6%	36 52.9%	65 47.8%
Male	39 57.4%	32 47.1%	71 52.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 1.5%	0 0%	1 0.7%
Asian	4 5.9%	3 4.4%	7 5.1%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 1.5%	3 4.4%	4 2.9%
White	62 91.2%	61 89.7%	123 90.4%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	1 1.5%	1 0.7%

Outcome Measures

1. Primary Outcome

Title	Progression Free Survival
Description	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
Time Frame	3-years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A- Vaccine Plus OPT-821	Arm B - OPT-821 Immunologic Adjuvant
Arm/Group Description	Trivalent ganglioside vaccine: 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	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 OPT-821: 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
Measure Participants	68	68
Median (95% Confidence Interval) [Days]	186	271

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	3 years
Arm/Group Title	Arm A- Vaccine Plus OPT-821		Arm B - OPT-821 Immunologic Adjuvant
Arm/Group Description	Trivalent ganglioside vaccine: 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		OPT-821: 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
All Cause Mortality
	Arm A- Vaccine Plus OPT-821		Arm B - OPT-821 Immunologic Adjuvant
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm A- Vaccine Plus OPT-821		Arm B - OPT-821 Immunologic Adjuvant
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/68 (5.9%)		8/68 (11.8%)
Blood and lymphatic system disorders
Anaemia	0/68 (0%)	0	1/68 (1.5%)	1
Cardiac disorders
Cardiomyopathy	0/68 (0%)	0	1/68 (1.5%)	1
Mitral valve disease	0/68 (0%)	0	1/68 (1.5%)	1
Gastrointestinal disorders
Gastrointestinal haemorrhage	0/68 (0%)	0	1/68 (1.5%)	1
General disorders
Death	1/68 (1.5%)	1	0/68 (0%)	0
Hepatobiliary disorders
Portal vein thrombosis	0/68 (0%)	0	1/68 (1.5%)	1
Immune system disorders
Anaphylactoid reaction	1/68 (1.5%)	1	0/68 (0%)	0
Infections and infestations
Catheter site cellulitis	0/68 (0%)	0	1/68 (1.5%)	1
Urinary tract infection	0/68 (0%)	0	1/68 (1.5%)	1
Injury, poisoning and procedural complications
Hip Fracture	1/68 (1.5%)	1	0/68 (0%)	0
Nervous system disorders
Cerebrovascular Accident	0/68 (0%)	0	1/68 (1.5%)	1
Skin and subcutaneous tissue disorders
Erythema	1/68 (1.5%)	1	0/68 (0%)	0
Other (Not Including Serious) Adverse Events
	Arm A- Vaccine Plus OPT-821		Arm B - OPT-821 Immunologic Adjuvant
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/68 (1.5%)		0/68 (0%)
Infections and infestations
Ear infection	1/68 (1.5%)	1	0/68 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Site shall withhold publication of Site's individual Study results for a period of 18 months following completion of the Study at all sites, or until after Sponsor's written confirmation that Sponsor will not publish a joint, multicenter publication, whichever occurs first.