Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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 September 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: September 30, 2014
Last verified: September 2014

January 25, 2012
September 30, 2014
March 2012
September 2016   (final data collection date for primary outcome measure)
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).
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).
Complete list of historical versions of study NCT01522820 on ClinicalTrials.gov Archive Site
  • 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.
  • 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 ]
Time to disease progression [ Time Frame: Up to 12 months post treatment ] [ Designated as safety issue: No ]
Not Provided
 
Vaccine Therapy With or Without Sirolimus in Treating Patients With NY-ESO-1 Expressing Solid Tumors
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

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. Is not yet known whether vaccine therapy works better when given with or without sirolimus in treating solid tumors.

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.

Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • 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
    Given intranodally
  • Drug: sirolimus
    Given PO or PEG
    Other Names:
    • AY 22989
    • Rapamune
    • rapamycin
    • SLM
  • Other: laboratory biomarker analysis
    Correlative studies
  • Other: pharmacological study
    Correlative studies
    Other Name: pharmacological studies
  • Experimental: Cohort 1a (vaccine therapy)
    Patients receive DEC-205-NY-ESO-1 fusion protein vaccine intranodally on days 1, 29, 57, and 113.
    Interventions:
    • Biological: DEC-205-NY-ESO-1 fusion protein vaccine
    • Other: laboratory biomarker analysis
    • Other: pharmacological study
  • 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.
    Interventions:
    • Biological: DEC-205-NY-ESO-1 fusion protein vaccine
    • Drug: sirolimus
    • Other: laboratory biomarker analysis
    • Other: pharmacological study
  • 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.
    Interventions:
    • Biological: DEC-205-NY-ESO-1 fusion protein vaccine
    • Drug: sirolimus
    • Other: laboratory biomarker analysis
    • Other: pharmacological study
  • 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.
    Interventions:
    • Biological: DEC-205-NY-ESO-1 fusion protein vaccine
    • Drug: sirolimus
    • Other: laboratory biomarker analysis
    • Other: pharmacological study
  • 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.
    Interventions:
    • Biological: DEC-205-NY-ESO-1 fusion protein vaccine
    • Drug: sirolimus
    • Other: laboratory biomarker analysis
    • Other: pharmacological study
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
30
Not Provided
September 2016   (final data collection date for primary outcome measure)

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, 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 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)
Both
18 Years and older
No
United States
 
NCT01522820
I 191511, NCI-2011-03568, 071614, I 191511, R01CA158318, P30CA016056
No
Roswell Park Cancer Institute
Roswell Park Cancer Institute
National Cancer Institute (NCI)
Principal Investigator: Kunle Odunsi Roswell Park Cancer Institute
Roswell Park Cancer Institute
September 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP