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

Study Overview

• Status: Completed
• Conditions: Sarcoma; Glioblastoma; Recurrent Ovarian Carcinoma; Recurrent Uterine Corpus Carcinoma; Anaplastic Oligoastrocytoma; Anaplastic Astrocytoma; Metastatic Renal Cell Cancer; Recurrent Lung Carcinoma; Recurrent Renal Cell Carcinoma; Stage IV Skin Melanoma; Recurrent Melanoma; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma; Metastatic Prostate Carcinoma; Stage II Uterine Corpus Cancer; Anaplastic Oligodendroglioma; Recurrent Bladder Carcinoma; Recurrent Breast Carcinoma; Recurrent Colorectal Carcinoma; Recurrent Esophageal Carcinoma; Recurrent Gastric Carcinoma; Recurrent Prostate Carcinoma; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Prostate Cancer; Estrogen Receptor Negative; Estrogen Receptor Positive; Recurrent Hepatocellular Carcinoma; Hormone-Resistant Prostate Cancer; Stage IIA Ovarian Cancer; Stage IIB Ovarian Cancer; Stage IIC Ovarian Cancer; Stage IIIA Ovarian Cancer; Stage IIIB Ovarian Cancer; Stage IIIC Ovarian Cancer; Stage IV Ovarian Cancer; Stage IV Esophageal Cancer; Recurrent Adult Brain Neoplasm; Stage IA Uterine Corpus Cancer; Stage IB Uterine Corpus Cancer; Stage IIIA Uterine Corpus Cancer; Stage IIIB Uterine Corpus Cancer; Stage IIIC Uterine Corpus Cancer; Stage IVA Uterine Corpus Cancer; Stage IVB Uterine Corpus Cancer; Stage IIB Skin Melanoma; Stage IIC Skin Melanoma; Stage IIIA Skin Melanoma; Stage IIA Lung Carcinoma; Stage IIB Lung Carcinoma; Stage IIIA Lung Carcinoma; Resectable Hepatocellular Carcinoma; Stage IA Ovarian Cancer; Stage IB Ovarian Cancer; Stage IC Ovarian Cancer; Stage IIB Esophageal Cancer; Stage IIIA Esophageal Cancer; Stage IIIB Esophageal Cancer; Stage IIIC Esophageal Cancer; Stage IV Bladder Urothelial Carcinoma
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Biological: DEC-205/NY-ESO-1 Fusion Protein CDX-1401; Drug: Sirolimus

Detailed Description

PRIMARY OBJECTIVES:

I. Determine the safety of DC205-NY-ESO-1 vaccine (DEC-205/NY-ESO-1 fusion protein CDX-1401) 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 CDX-1401 intranodally on days 1, 29, 57, and 113.

COHORT 1b: Patients receive DEC-205/NY-ESO-1 fusion protein CDX-1401 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 CDX-1401 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 CDX-1401 as in Cohort 1a and sirolimus PO or PEG on days 1-84.

COHORT 2: Patients receive DEC-205/NY-ESO-1 fusion protein CDX-1401 as in the Cohort (1a-1d) that is determined to be safe and produces optimal immunological effects and sirolimus PO on days 1-14 as in Cohort 1b dose.

After completion of study treatment, patients are followed up at 6 weeks, 6 months and 12 months.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1a (vaccine therapy); Patients receive DEC-205/NY-ESO-1 fusion protein CDX-1401 protein vaccine intranodally on days 1, 29, 57, and 113.	Other: Laboratory Biomarker Analysis; Correlative studies; Other: Pharmacological Study; Correlative studies; Biological: DEC-205/NY-ESO-1 Fusion Protein CDX-1401; Given intranodally; Other Names: CDX-1401
Experimental: Cohort 1b (vaccine therapy and immunotherapy); Patients receive DEC-205/NY-ESO-1 fusion protein CDX-1401 as in Cohort 1a and sirolimus PO or PEG on days 1-14, 29-42, and 57-70.	Other: Laboratory Biomarker Analysis; Correlative studies; Other: Pharmacological Study; Correlative studies; Biological: DEC-205/NY-ESO-1 Fusion Protein CDX-1401; Given intranodally; Other Names: CDX-1401; Drug: Sirolimus; Given PO or PEG; Other Names: Rapamune; AY 22989; RAPA; RAPAMYCIN; SILA 9268A; WY-090217
Experimental: Cohort 1c (vaccine therapy and immunotherapy); Patients receive DEC-205/NY-ESO-1 fusion protein CDX-1401 vaccine as in Cohort 1a and sirolimus PO or PEG on days 15-28, 43-56, and 71-84.	Other: Laboratory Biomarker Analysis; Correlative studies; Other: Pharmacological Study; Correlative studies; Biological: DEC-205/NY-ESO-1 Fusion Protein CDX-1401; Given intranodally; Other Names: CDX-1401; Drug: Sirolimus; Given PO or PEG; Other Names: Rapamune; AY 22989; RAPA; RAPAMYCIN; SILA 9268A; WY-090217
Experimental: Cohort 1d (vaccine therapy and immunotherapy); Patients receive DEC-205/NY-ESO-1 fusion protein CDX-1401 as in Cohort 1a and sirolimus PO or PEG on days 1-84.	Other: Laboratory Biomarker Analysis; Correlative studies; Other: Pharmacological Study; Correlative studies; Biological: DEC-205/NY-ESO-1 Fusion Protein CDX-1401; Given intranodally; Other Names: CDX-1401; Drug: Sirolimus; Given PO or PEG; Other Names: Rapamune; AY 22989; RAPA; RAPAMYCIN; SILA 9268A; WY-090217
Experimental: Cohort 2 (vaccine therapy with or without immunotherapy); Patients receive DEC-205/NY-ESO-1 fusion protein CDX-1401 as in the Cohort (1a-1d) that is determined to be safe and produces optimal immunological effects and sirolimus PO on days 1-14 as in Cohort 1b dose.	Other: Laboratory Biomarker Analysis; Correlative studies; Other: Pharmacological Study; Correlative studies; Biological: DEC-205/NY-ESO-1 Fusion Protein CDX-1401; Given intranodally; Other Names: CDX-1401; Drug: Sirolimus; Given PO or PEG; Other Names: Rapamune; AY 22989; RAPA; RAPAMYCIN; SILA 9268A; WY-090217

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events in patients receiving the DEC-205/NY-ESO-1 fusion protein CDX-1401 with and without sirolimus, as evaluated according to the NCI CTCAE scale version 4.0	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).	Up to 12 months post-treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
NY-ESO-1 specific cellular immunity	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.	Up to 12 months post-treatment
NY-ESO-1 specific humoral immunity	ANCOVA model with post-treatment levels modeled as a function pretreatment levels and main effects corresponding to the 3 + 3 design.	Up to 12 months post-treatment

Other Outcome Measures

Outcome Measure	Time Frame
Time to disease progression	Up to 12 months post treatment

Collaborators and Investigators

• Sponsor: Roswell Park Cancer Institute
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Kunle Odunsi, Roswell Park Cancer Institute

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (Actual): July 1, 2016
• Study Completion (Actual): July 1, 2016

Study Registration Dates

• First Submitted: January 25, 2012
• First Submitted That Met QC Criteria: January 30, 2012
• First Posted (Estimate): February 1, 2012

Study Record Updates

• Last Update Posted (Estimate): October 4, 2016
• Last Update Submitted That Met QC Criteria: October 3, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Skin Diseases; Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms; Lung Diseases; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Urinary Bladder Diseases; Genital Neoplasms, Female; Endocrine System Diseases; Disease Attributes; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Endocrine Gland Neoplasms; Genital Neoplasms, Male; Breast Diseases; Liver Diseases; Prostatic Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Head and Neck Neoplasms; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Kidney Neoplasms; Colonic Diseases; Intestinal Diseases; Liver Neoplasms; Intestinal Neoplasms; Rectal Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Esophageal Diseases; Neuroendocrine Tumors; Nevi and Melanomas; Carcinoma, Renal Cell; Stomach Neoplasms; Breast Neoplasms; Prostatic Neoplasms; Lung Neoplasms; Carcinoma; Glioblastoma; Carcinoma, Hepatocellular; Colorectal Neoplasms; Recurrence; Ovarian Neoplasms; Urinary Bladder Neoplasms; Brain Neoplasms; Melanoma; Carcinoma, Ovarian Epithelial; Skin Neoplasms; Astrocytoma; Esophageal Neoplasms; Oligodendroglioma; Physiological Effects of Drugs; Anti-Infective Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Sirolimus
• Other Study ID Numbers: I 191511 (Other Identifier: Roswell Park Cancer Institute); P30CA016056 (U.S. NIH Grant/Contract); R01CA158318 (U.S. NIH Grant/Contract); NCI-2011-03568 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); 071614