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
Phase 1
18 Years
N/A
18 Years
N/A
Open (Enrolling)
Both
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
Both
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
Trial Information
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
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.
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
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
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
Outcome Description:
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).
Outcome Time Frame:
28 days
Safety Issue:
Yes
Principal Investigator
Kunle Odunsi
Investigator Role:
Principal Investigator
Investigator Affiliation:
Roswell Park Cancer Institute
Authority:
United States: Food and Drug Administration
Study ID:
I 191511
NCT ID:
NCT01522820
Start Date:
March 2012
Completion Date:
Related Keywords:
- 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
- Astrocytoma
- Urinary Bladder Neoplasms
- Brain Neoplasms
- Breast Neoplasms
- Carcinoma
- Colonic Neoplasms
- Rectal Neoplasms
- Carcinoma, Non-Small-Cell Lung
- Carcinoma, Renal Cell
- Chondrosarcoma
- Esophageal Diseases
- Esophageal Neoplasms
- Glioblastoma
- Glioma
- Leiomyosarcoma
- Liver Neoplasms
- Lung Neoplasms
- Stomach Neoplasms
- Melanoma
- Oligodendroglioma
- Osteosarcoma
- Prostatic Neoplasms
- Sarcoma, Kaposi
- Mast-Cell Sarcoma
- Small Cell Lung Carcinoma
- Neoplasms, Germ Cell and Embryonal
- Neuroectodermal Tumors
- Neuroectodermal Tumors, Primitive
- Sarcoma, Clear Cell
- Gliosarcoma
- Sarcoma
- Breast Neoplasms, Male
- Germinoma
- Ovarian Neoplasms
- Neoplasms
- Sarcoma, Ewing's
- Neuroectodermal Tumors, Primitive, Peripheral
- Neoplasms, Glandular and Epithelial
- Carcinoma, Hepatocellular
Name | Location |
|---|---|
| Roswell Park Cancer Institute | Buffalo, New York 14263 |
