Vaccine Therapy With or Without Sirolimus in Treating Patients With NY-ESO-1 Expressing Solid Tumors

• Status: Completed
• Trial end date: 2016-07-01
• Target enrollment: 0
• Participant gender: All

Summary

This phase I trial studies the side effects and best schedule of vaccine therapy with or without sirolimus in treating patients with cancer-testis antigen (NY-ESO-1) expressing solid tumors. Biological therapies, such as sirolimus, may stimulate the immune system in different ways and stop tumor cells from growing. Vaccines made from a person's white blood cells mixed with tumor proteins may help the body build an effective immune response to kill tumor cells that express NY-ESO-1. Infusing the vaccine directly into a lymph node may cause a stronger immune response and kill more tumor cells. It is not yet known whether vaccine therapy works better when given with or without sirolimus in treating solid tumors.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Roswell Park Cancer Institute
• Collaborator: National Cancer Institute (NCI)
• Treatments: Everolimus; Sirolimus; Vaccines

Criteria

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)