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

Purpose

This phase I trial studies the side effects and best schedule of vaccine therapy when given together with or without sirolimus in treating patients with 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. Is not yet known whether vaccine therapy is more effective when given with or without sirolimus in treating solid tumors

Condition	Intervention	Phase
Adult Anaplastic Astrocytoma Adult Anaplastic Oligodendroglioma Adult Giant Cell Glioblastoma Adult Glioblastoma Adult Gliosarcoma Adult Mixed Glioma Adult Primary Hepatocellular Carcinoma Chondrosarcoma Clear Cell Sarcoma of the Kidney Conjunctival Kaposi Sarcoma Estrogen Receptor-negative Breast Cancer Estrogen Receptor-positive Breast Cancer Hormone-resistant Prostate Cancer Limited Stage Small Cell Lung Cancer Localized Resectable Adult Primary Liver Cancer Male Breast Cancer Mast Cell Sarcoma Ovarian Sarcoma Recurrent Adult Brain Tumor Recurrent Adult Primary Liver Cancer Recurrent Adult Soft Tissue Sarcoma Recurrent Bladder Cancer Recurrent Breast Cancer Recurrent Colon Cancer Recurrent Esophageal Cancer Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor Recurrent Gastric Cancer Recurrent Kaposi Sarcoma Recurrent Melanoma Recurrent Non-small Cell Lung Cancer Recurrent Osteosarcoma Recurrent Ovarian Epithelial Cancer Recurrent Ovarian Germ Cell Tumor Recurrent Prostate Cancer Recurrent Rectal Cancer Recurrent Renal Cell Cancer Recurrent Small Cell Lung Cancer Recurrent Uterine Sarcoma Small Intestine Leiomyosarcoma Stage I Colon Cancer Stage I Rectal Cancer Stage I Uterine Sarcoma Stage IA Breast Cancer Stage IA Gastric Cancer Stage IA Ovarian Epithelial Cancer Stage IA Ovarian Germ Cell Tumor Stage IB Breast Cancer Stage IB Gastric Cancer Stage IB Ovarian Epithelial Cancer Stage IB Ovarian Germ Cell Tumor Stage IC Ovarian Epithelial Cancer Stage IC Ovarian Germ Cell Tumor Stage II Breast Cancer Stage II Uterine Sarcoma Stage IIA Colon Cancer Stage IIA Gastric Cancer Stage IIA Non-small Cell Lung Cancer Stage IIA Ovarian Epithelial Cancer Stage IIA Ovarian Germ Cell Tumor Stage IIA Rectal Cancer Stage IIB Colon Cancer Stage IIB Esophageal Cancer Stage IIB Gastric Cancer Stage IIB Melanoma Stage IIB Non-small Cell Lung Cancer Stage IIB Ovarian Epithelial Cancer Stage IIB Ovarian Germ Cell Tumor Stage IIB Rectal Cancer Stage IIC Colon Cancer Stage IIC Melanoma Stage IIC Ovarian Epithelial Cancer Stage IIC Ovarian Germ Cell Tumor Stage IIC Rectal Cancer Stage III Uterine Sarcoma Stage IIIA Breast Cancer Stage IIIA Colon Cancer Stage IIIA Esophageal Cancer Stage IIIA Gastric Cancer Stage IIIA Melanoma Stage IIIA Non-small Cell Lung Cancer Stage IIIA Ovarian Epithelial Cancer Stage IIIA Ovarian Germ Cell Tumor Stage IIIA Rectal Cancer Stage IIIB Breast Cancer Stage IIIB Colon Cancer Stage IIIB Esophageal Cancer Stage IIIB Gastric Cancer Stage IIIB Melanoma Stage IIIB Ovarian Epithelial Cancer Stage IIIB Ovarian Germ Cell Tumor Stage IIIB Rectal Cancer Stage IIIC Breast Cancer Stage IIIC Colon Cancer Stage IIIC Esophageal Cancer Stage IIIC Gastric Cancer Stage IIIC Melanoma Stage IIIC Ovarian Epithelial Cancer Stage IIIC Ovarian Germ Cell Tumor Stage IIIC Rectal Cancer Stage IV Bladder Cancer Stage IV Esophageal Cancer Stage IV Gastric Cancer Stage IV Melanoma Stage IV Ovarian Epithelial Cancer Stage IV Ovarian Germ Cell Tumor Stage IV Prostate Cancer Stage IV Renal Cell Cancer Stage IV Uterine Sarcoma Stage IVA Colon Cancer Stage IVA Rectal Cancer Stage IVB Colon Cancer Stage IVB Rectal Cancer Unspecified Adult Solid Tumor, Protocol Specific	Drug: sirolimus Other: laboratory biomarker analysis Biological: DEC-205-NY-ESO-1 fusion protein vaccine	Phase 1

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase I Clinical Trial of mTOR Inhibition With Rapamycin for Enhancing Intranodal Dendritic Cell Vaccine Induced Anti-Tumor Immunity In Patients With NY-ESO-1 Expressing Solid Tumors

Resource links provided by NLM:

Further study details as provided by Roswell Park Cancer Institute:

Primary Outcome Measures:

Safety of the DEC-205-NY-ESO-1 fusion protein vaccine, with and without sirolimus, as evaluated according to the NCI CTCAE scale version 4.0 [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
The safe schedule of the combinatorial regimen is established at the dose before 2/6 patients experience dose-limiting toxicity. Estimated using a one-sided, 95%, exact binomial confidence interval (Clopper-Pearson).

Secondary Outcome Measures:

NY-ESO-1-specific CD8- and CD4+ T cell antibody response in peripheral blood samples as measured by ELISA [ Time Frame: Baseline ] [ Designated as safety issue: No ]
NY-ESO-1-specific CD8- and CD4+ T cell antibody response in peripheral blood samples as measured by ELISA [ Time Frame: Days 29 ] [ Designated as safety issue: No ]
NY-ESO-1-specific CD8- and CD4+ T cell antibody response in peripheral blood samples as measured by ELISA [ Time Frame: Day 57 ] [ Designated as safety issue: No ]
NY-ESO-1-specific CD8- and CD4+ T cell antibody response in peripheral blood samples as measured by ELISA [ Time Frame: Day 113 ] [ Designated as safety issue: No ]
NY-ESO-1-specific CD8- and CD4+ T cell antibody response in peripheral blood samples as measured by ELISA [ Time Frame: Day 120 ] [ Designated as safety issue: No ]
NY-ESO-1-specific CD8- and CD4+ T cell antibody response in peripheral blood samples as measured by ELISA [ Time Frame: Day 143 ] [ Designated as safety issue: No ]
Frequency of CD4+CD25+FOXP3+ regulatory T-cells in peripheral blood samples as measured by IFN-gamma release ELISPOT and Intracellular Cytokine Staining (ICS) [ Time Frame: Baseline ] [ Designated as safety issue: No ]
Frequency of CD4+CD25+FOXP3+ regulatory T-cells in peripheral blood samples as measured by IFN-gamma release ELISPOT ICS [ Time Frame: Day 29 ] [ Designated as safety issue: No ]
Frequency of CD4+CD25+FOXP3+ regulatory T-cells in peripheral blood samples as measured by IFN-gamma release ELISPOT and ICS [ Time Frame: Day 57 ] [ Designated as safety issue: No ]
Frequency of CD4+CD25+FOXP3+ regulatory T-cells in peripheral blood samples as measured by IFN-gamma release ELISPOT and ICS [ Time Frame: Day 113 ] [ Designated as safety issue: No ]
Frequency of CD4+CD25+FOXP3+ regulatory T-cells in peripheral blood samples as measured by IFN-gamma release ELISPOT and ICS [ Time Frame: Day 120 ] [ Designated as safety issue: No ]
Frequency of CD4+CD25+FOXP3+ regulatory T-cells in peripheral blood samples as measured by IFN-gamma release ELISPOT and ICS [ Time Frame: Day 143 ] [ Designated as safety issue: No ]
Time to disease progression assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. [ Time Frame: Day 57 ] [ Designated as safety issue: No ]
Time to disease progression assessed according to the RECIST 1.1. [ Time Frame: Day 143 ] [ Designated as safety issue: No ]

Estimated Enrollment:	20
Study Start Date:	March 2012
Estimated Primary Completion Date:	September 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Cohort 1a (vaccine therapy) Patients receive intranodal DEC-205-NY-ESO-1 fusion protein vaccine on days 1, 29, 57, and 113.	Other: laboratory biomarker analysis Correlative studies Biological: DEC-205-NY-ESO-1 fusion protein vaccine Given intranodally
Experimental: Cohort 1b (vaccine therapy and immunotherapy) Patients receive DEC-205-NY-ESO-1 fusion protein vaccine as in Cohort 1a and sirolimus PO on days 1-14, 29-42, and 57-70.	Drug: sirolimus Given PO Other Names: AY 22989 Rapamune rapamycin SLM Other: laboratory biomarker analysis Correlative studies Biological: DEC-205-NY-ESO-1 fusion protein vaccine Given intranodally
Experimental: Cohort 1c (vaccine therapy and immunotherapy) Patients receive DEC-205-NY-ESO-1 fusion protein vaccine as in Cohort 1a and sirolimus PO on days 15-28, 43-56, and 71-84.	Drug: sirolimus Given PO Other Names: AY 22989 Rapamune rapamycin SLM Other: laboratory biomarker analysis Correlative studies Biological: DEC-205-NY-ESO-1 fusion protein vaccine Given intranodally
Experimental: Cohort 1d (vaccine therapy and immunotherapy) Patients receive DEC-205-NY-ESO-1 fusion protein vaccine as in Cohort 1a and sirolimus PO on days 1-84.	Drug: sirolimus Given PO Other Names: AY 22989 Rapamune rapamycin SLM Other: laboratory biomarker analysis Correlative studies Biological: DEC-205-NY-ESO-1 fusion protein vaccine Given intranodally
Experimental: Cohort 2 (vaccine therapy with or without immunotherapy) Patients receive treatment as in the Cohort (1a-1d) that is determined to be safe and produces optimal immunological effects.	Drug: sirolimus Given PO Other Names: AY 22989 Rapamune rapamycin SLM Other: laboratory biomarker analysis Correlative studies Biological: DEC-205-NY-ESO-1 fusion protein vaccine Given intranodally

Detailed Description:

PRIMARY OBJECTIVES: I. Determine the safety of DC205-NY-ESO-1 vaccine (DEC-205-NY-ESO-1 fusion protein vaccine) 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 intranodal DEC-205-NY-ESO-1 fusion protein vaccine on days 1, 29, 57, and 113. COHORT 1b: Patients receive DEC-205-NY-ESO-1 fusion protein vaccine 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 vaccine as in Cohort 1a and sirolimus PO on days 15-28, 43-56, and 71-84. COHORT 1d: Patients receive DEC-205-NY-ESO-1 fusion protein vaccine as in Cohort 1a and sirolimus PO on days 1-84. COHORT 2: Patients receive treatment as in the Cohort (1a-1d) that is determined to be safe and produces optimal immunological effects. After completion of study treatment, patients are followed up at 30 days.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients with solid tumors at high risk of recurrence or with minimal residual disease; there may or may not be measurable or symptomatic disease (included are patients with bladder, brain, breast, esophageal, gastrointestinal, hepatocellular, kidney, lungs, melanoma, ovarian, prostate, sarcomas, and uterine
Any human leukocyte antigen (HLA) type
Tumor expression of NY-ESO-1 or LAGE-1 by immunohistochemistry (IHC) and/or reverse transcription polymerase chain reaction (RTPCR)
Life expectancy > 6 months
Hematology and biochemistry laboratory results within the limits normally expected for the patient population, without evidence of major organ failure
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 glutamic pyruvate transaminase [SGPT]/alanine aminotransferase [ALT]) =< 3 x ULN - Serum creatinine =< 2 x ULN
PT/INR <= 1.5. Patients receiving anticoagulation therapy, PT/INR <=3.
No immunodeficiency
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
Demonstrate the ability to swallow and retain oral medication
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 autoimmune disease (e.g., thyroiditis, lupus) except vitiligo
Concomitant systemic treatment with corticosteroids, anti-histamine or non-steroidal anti-inflammatory drugs, Aspirin > 325 mg; specific 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 (NYHA Class III or IV) within 6 months
Participation in any other clinical trial involving another investigational agent within 4 weeks prior to first dosing of study agent
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
Immunocompromised patients, including patients known to be human immunodeficiency virus (HIV) positive and/or acute or chronic hepatitis (hepatitis B surface antigen [HBsAg]) positive or hepatitis C virus (anti-HBC) positive; patients suspected of being immunodeficient based on laboratory studies or clinical history will have further evaluation prior to study enrollment
Known hypersensitivity to sirolimus
Any condition which in the Investigator's opinion deems the patient an unsuitable candidate to receive study drug
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
Received an investigational agent within 30 days prior to enrollment

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01522820

Locations

United States, New York
Roswell Park Cancer Institute	Recruiting
Buffalo, New York, United States, 14263
Contact: Roswell Park 877-275-7724 ASKRPCI@RoswellPark.org
Principal Investigator: Kunle Odunsi

Sponsors and Collaborators

Roswell Park Cancer Institute

Investigators

Principal Investigator:

Kunle Odunsi

Roswell Park Cancer Institute

More Information

No publications provided

Responsible Party:	Roswell Park Cancer Institute
ClinicalTrials.gov Identifier:	NCT01522820 History of Changes
Other Study ID Numbers:	I 191511, NCI-2011-03568
Study First Received:	January 25, 2012
Last Updated:	March 5, 2013
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Urinary Bladder Neoplasms
Brain Neoplasms
Breast Neoplasms
Colonic Neoplasms
Rectal Neoplasms
Esophageal Neoplasms
Liver Neoplasms
Lung Neoplasms
Stomach Neoplasms
Prostatic Neoplasms
Neoplasms, Germ Cell and Embryonal
Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive
Breast Neoplasms, Male
Ovarian Neoplasms

Neoplasms
Neuroectodermal Tumors, Primitive, Peripheral
Neoplasms, Glandular and Epithelial
Neoplasms, Neuroepithelial
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Central Nervous System Neoplasms
Nervous System Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms

ClinicalTrials.gov processed this record on June 17, 2013