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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Roswell Park Cancer Institute
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Roswell Park Cancer Institute
ClinicalTrials.gov Identifier:
NCT01522820
First received: January 25, 2012
Last updated: August 5, 2014
Last verified: August 2014
  Purpose

This phase I trial studies the side effects and best schedule of vaccine therapy 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
Biological: DEC-205-NY-ESO-1 fusion protein vaccine
Drug: sirolimus
Other: laboratory biomarker analysis
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:
  • Incidence of adverse events in patients receiving 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: Up to 12 months post-treatment ] [ 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 cellular immunity [ Time Frame: Up to 12 months post-treatment ] [ Designated as safety issue: No ]
    Analyzed via an analysis-of-covariance (ANCOVA) model with post-treatment levels modeled as a function pretreatment levels and main effects corresponding to the 3 + 3 design.

  • NY-ESO-1 specific humoral immunity [ Time Frame: Up to 12 months post-treatment ] [ Designated as safety issue: No ]
    ANCOVA model with post-treatment levels modeled as a function pretreatment levels and main effects corresponding to the 3 + 3 design.


Other Outcome Measures:
  • Time to disease progression [ Time Frame: Up to 12 months post treatment ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: March 2012
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1a (vaccine therapy)
Patients receive DEC-205-NY-ESO-1 fusion protein vaccine intranodally on days 1, 29, 57, and 113.
Biological: DEC-205-NY-ESO-1 fusion protein vaccine
Given intranodally
Other: laboratory biomarker analysis
Correlative studies
Experimental: Cohort 1b (vaccine therapy and immunotherapy)
Patients receive DEC-205-NY-ESO-1 fusion protein vaccine as in Cohort 1a and sirolimus PO or PEG on days 1-14, 29-42, and 57-70.
Biological: DEC-205-NY-ESO-1 fusion protein vaccine
Given intranodally
Drug: sirolimus
Given PO or PEG
Other Names:
  • AY 22989
  • Rapamune
  • rapamycin
  • SLM
Other: laboratory biomarker analysis
Correlative studies
Experimental: Cohort 1c (vaccine therapy and immunotherapy)
Patients receive DEC-205-NY-ESO-1 fusion protein vaccine as in Cohort 1a and sirolimus PO or PEG on days 15-28, 43-56, and 71-84.
Biological: DEC-205-NY-ESO-1 fusion protein vaccine
Given intranodally
Drug: sirolimus
Given PO or PEG
Other Names:
  • AY 22989
  • Rapamune
  • rapamycin
  • SLM
Other: laboratory biomarker analysis
Correlative studies
Experimental: Cohort 1d (vaccine therapy and immunotherapy)
Patients receive DEC-205-NY-ESO-1 fusion protein vaccine as in Cohort 1a and sirolimus PO or PEG on days 1-84.
Biological: DEC-205-NY-ESO-1 fusion protein vaccine
Given intranodally
Drug: sirolimus
Given PO or PEG
Other Names:
  • AY 22989
  • Rapamune
  • rapamycin
  • SLM
Other: laboratory biomarker analysis
Correlative studies
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.
Biological: DEC-205-NY-ESO-1 fusion protein vaccine
Given intranodally
Drug: sirolimus
Given PO or PEG
Other Names:
  • AY 22989
  • Rapamune
  • rapamycin
  • SLM
Other: laboratory biomarker analysis
Correlative studies

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 DEC-205-NY-ESO-1 fusion protein vaccine intranodally 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 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 vaccine as in Cohort 1a and sirolimus PO or PEG 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 6 weeks, 6 months and 12 months.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 mammalian target of rapamycin (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 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, 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 glutamic 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 (FEV)1 > 50% and diffusion lung capacity for carbon monoxide (DLCO) > 50%
  • Pulse oximetry: oxygen (O2) saturation >= 90% on room air
  • Electrocardiogram, showing no evidence of congestive heart failure, myocardial infarction, and cardiomyopathy
  • 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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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    716-845-3497    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, I 191511, P30CA016056
Study First Received: January 25, 2012
Last Updated: August 5, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Sarcoma, Kaposi
Astrocytoma
Urinary Bladder Neoplasms
Brain Neoplasms
Breast Neoplasms
Carcinoma
Colonic Neoplasms
Rectal Neoplasms
Carcinoma, Non-Small-Cell Lung
Carcinoma, Renal Cell
Chondrosarcoma
Esophageal Neoplasms
Glioblastoma
Glioma
Leiomyosarcoma
Liver Neoplasms
Lung Neoplasms
Stomach Neoplasms
Melanoma
Oligodendroglioma
Osteosarcoma
Prostatic Neoplasms
Mast-Cell Sarcoma
Small Cell Lung Carcinoma
Neoplasms, Germ Cell and Embryonal
Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive
Sarcoma, Clear Cell
Gliosarcoma
Sarcoma

ClinicalTrials.gov processed this record on August 28, 2014