Clinical Trial Finder

Inclusion Criteria:

• - Patients with any solid tumors at high risk of recurrence or with minimal residual disease; there may or may not be measurable or symptomatic disease (i.e., patients with bladder, brain, breast, esophageal, gastrointestinal, hepatocellular, kidney, lungs, melanoma, ovarian, prostate, sarcomas, and uterine) - Cancer types: - Prostate cancer: patients with metastatic, castrate refractory prostate cancer; the use of luteinizing hormone-releasing hormone (LHRH) agonist is allowed.

• - Kidney cancer: patients with metastatic kidney cancer; prior therapies with cytokines, vascular endothelial growth factor (VEGF) and mechanistic target of rapamycin (serine/threonine kinase) (mTOR) inhibitors are allowed.

• - Bladder cancer: patients with metastatic urothelial carcinoma; prior cisplatin-based therapies are allowed.

• - Ovarian cancer: eligible patients may have asymptomatic residual measurable disease on physical examination and/or computed tomography (CT) scan, and/or may have an elevated cancer antigen (CA)-125; or may be in complete clinical remission after treatment for primary or recurrent disease.

• - Brain tumors: histologic proof of one of the following: glioblastoma multiforme, anaplastic astrocytoma, anaplastic oligodendroglioma or anaplastic mixed glioma or anaplastic oligoastrocytoma; patients who have had recent cranial surgery are eligible for inclusion, but the vaccine may not be administered prior to postoperative day 14.

• - Uterine cancer: patients with advanced (stages II-IV) or recurrent disease who have completed standard therapy, currently no evidence of disease (NED) or with minimal residual disease; patients with stage I uterine serous carcinomas or sarcomas are also eligible after completion of standard therapy.

• - Breast cancer: patients can enter study after completion of all chemotherapy (including trastuzumab), radiation, and breast/axillary surgery; patients may participate while on endocrine therapy; stages I-III patients with the following characteristics: - Estrogen-receptor (ER) negative with positive lymph nodes; ER negative with negative nodes if tumor > 2 cm; ER positive with positive lymph nodes; and ER positive with negative lymph nodes and tumor > 5 cm.

• - Sarcomas: patients with sarcomas of any site, who have completed standard therapy, and are in remission, or have minimal disease burden.

• - Lungs: resected patients with hilar or ipsilateral mediastinal nodal disease (i.e., a subset of patients with stage II and IIIA disease); and patients with residual disease on imaging after definitive radiation or chemoradiation therapy.

• - Esophageal: resected patients with any nodal (i.e., thoracic or abdominal) disease; and patients with residual disease on imaging after definitive chemoradiation therapy.

• - Melanoma: stage IIB, stage IIC, and stage III who have completed planned definitive therapy for their disease including radiotherapy and/or interferon; patients declining interferon or with contra-indications to interferon will also be eligible provided they meet requisite criteria for this study (i.e., non-measurable disease); stage IV melanoma of M1a sub-type only, who are not candidates for additional therapy of curative potential (i.e., small volume disease; may be measurable or evaluable); and stage IV melanoma, NED, status post (s/p) complete resection of known sites of disease (i.e., non-measurable disease) - Hepatocellular carcinoma (HCC): patients who have been treated with surgical resection for HCC; and following chemoembolization as adjuvant therapy for HCC.

• - Gastrointestinal: patients who have completed standard therapies for gastric and colorectal cancers, and deemed to be at high-risk of relapse.

• - Any human leukocyte antigen (HLA) type; historic HLA typing is permitted.

• - Tumor expression of NY-ESO-1 or LAGE-1 by immunohistochemistry (IHC) and/or reverse transcription polymerase chain reaction (RTPCR) - Life expectancy > 6 months.

• - Absolute neutrophil count (ANC) >= 1,000/uL.

• - Platelets (PLT) >= 75,000/uL.

• - Hemoglobin (Hgb) >= 8 g/dL.

• - Total bilirubin =< 1.5 x upper limit of normal (ULN) - Serum aspartate aminotransferase (serum glutamic oxaloacetic transaminase [SGOT]/aspartate aminotransferase [AST]) or serum alanine aminotransferase (serum glutamate pyruvate transaminase [SGPT]/alanine aminotransferase [ALT]) =< 3 x ULN.

• - Serum creatinine =< 2 x ULN.

• - Prothrombin time (PT)/international normalized ratio (INR) =< 1.5 x ULN; patients receiving anticoagulation therapy, PT/INR =< 3.

• - Pulmonary function tests: forced expiratory volume in one second (FEV1) > 50% and diffusion capacity of the lungs for carbon monoxide (DLCO) > 50% - Pulse oximetry: oxygen (O2) saturation >= 90% on room air.

• - Electrocardiogram, showing no clinical significant or acute abnormality.

• - Have been informed of other treatment options.

• - Patient or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure.

• - Have an Eastern Cooperative Oncology Group (ECOG) performance status of =< 2.

• - Patients of child-bearing potential must agree to use acceptable contraceptive methods (e.g., double barrier) during treatment.

Exclusion Criteria:

• - Metastatic disease to the central nervous system for which other therapeutic options, including radiotherapy, may be available.

• - Other serious illnesses (e.g., serious infections requiring antibiotics, bleeding disorders) - History of severe autoimmune disorders requiring use of steroids or other immunosuppressives.

• - Concomitant systemic treatment with corticosteroids, anti-histamine or non-steroidal anti-inflammatory drugs, aspirin > 325 mg; specific cyclooxygenase (COX)-2 inhibitors are permitted.

• - Chemotherapy, radiation therapy, or immunotherapy within 4 weeks prior to first dosing of study agent (6 weeks for nitrosoureas); concomitant hormonal therapies for breast and prostate cancers are allowed.

• - Clinically significant heart disease (New York Heart Association [NYHA] class III or IV) within 6 months.

• - Mental impairment that may compromise the ability to give informed consent and comply with the requirements of the study.

• - Lack of availability of a patient for immunological and clinical follow-up assessment.

• - Known pulmonary hypertension.

• - Known hypersensitivity to sirolimus.

• - Evidence of current drug or alcohol abuse or psychiatric impairment, which in the investigator's opinion will prevent completion of the protocol therapy or follow-up.

• - Pregnant or nursing female patients.

• - Unwilling or unable to follow protocol requirements.

• - Any condition which in the investigator's opinion deems the patient an unsuitable candidate to receive study drug; (i.e., any significant medical illness or abnormal laboratory finding that would, in the investigator's judgment, increase the subject's risk by participating in this study) - Received an investigational agent within 30 days prior to enrollment.

- Known hepatitis B, hepatitis C, or human immunodeficiency virus (HIV)

PRIMARY OBJECTIVES:

• I. Determine the safety of DC205-NY-ESO-1 vaccine (DEC-205/NY-ESO-1 fusion protein CDX-1401) with and without sirolimus.

Toxicity as defined by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. SECONDARY OBJECTIVES:

• I. Assess the NY-ESO-1 specific cellular and humoral immunity: - Peripheral blood NY-ESO-1 specific cluster of differentiation (CD)8+ and CD4+ T-cells.

• - Peripheral blood NY-ESO-1 specific antibodies.

• - Peripheral blood frequency of CD4+CD25+forkhead box P3 (FOXP3)+ regulatory T-cells.

TERTIARY OBJECTIVES:

• I. Explore time to disease progression.

OUTLINE: Patients undergo standard collection of peripheral white blood cells via leukapheresis over 90-240 minutes for vaccine preparation. Patients are assigned sequentially to Cohorts 1a-1d. COHORT 1a: Patients receive DEC-205/NY-ESO-1 fusion protein CDX-1401 intranodally on days 1, 29, 57, and 113. COHORT 1b: Patients receive DEC-205/NY-ESO-1 fusion protein CDX-1401 as in Cohort 1a and sirolimus orally (PO) on days 1-14, 29-42, and 57-70. COHORT 1c: Patients receive DEC-205/NY-ESO-1 fusion protein CDX-1401 as in Cohort 1a and sirolimus PO or percutaneous endoscopic gastrostomy (PEG) tube on days 15-28, 43-56, and 71-84. COHORT 1d: Patients receive DEC-205/NY-ESO-1 fusion protein CDX-1401 as in Cohort 1a and sirolimus PO or PEG on days 1-84. COHORT 2: Patients receive DEC-205/NY-ESO-1 fusion protein CDX-1401 as in the Cohort (1a-1d) that is determined to be safe and produces optimal immunological effects and sirolimus PO on days 1-14 as in Cohort 1b dose. After completion of study treatment, patients are followed up at 6 weeks, 6 months and 12 months.

Arms

Experimental: Cohort 1a (vaccine therapy)

Patients receive DEC-205/NY-ESO-1 fusion protein CDX-1401 protein vaccine intranodally on days 1, 29, 57, and 113.

Experimental: Cohort 1b (vaccine therapy and immunotherapy)

Patients receive DEC-205/NY-ESO-1 fusion protein CDX-1401 as in Cohort 1a and sirolimus PO or PEG on days 1-14, 29-42, and 57-70.

Experimental: Cohort 1c (vaccine therapy and immunotherapy)

Patients receive DEC-205/NY-ESO-1 fusion protein CDX-1401 vaccine as in Cohort 1a and sirolimus PO or PEG on days 15-28, 43-56, and 71-84.

Experimental: Cohort 1d (vaccine therapy and immunotherapy)

Patients receive DEC-205/NY-ESO-1 fusion protein CDX-1401 as in Cohort 1a and sirolimus PO or PEG on days 1-84.

Experimental: Cohort 2 (vaccine therapy with or without immunotherapy)

Patients receive DEC-205/NY-ESO-1 fusion protein CDX-1401 as in the Cohort (1a-1d) that is determined to be safe and produces optimal immunological effects and sirolimus PO on days 1-14 as in Cohort 1b dose.

Interventions

Biological: - DEC-205/NY-ESO-1 Fusion Protein CDX-1401

Given intranodally

Other: - Laboratory Biomarker Analysis

Correlative studies

Other: - Pharmacological Study

Correlative studies

Drug: - Sirolimus

Given PO or PEG