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

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.

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.