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
5 other identifiers
interventional
18
1 country
1
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Mar 2012
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 25, 2012
CompletedFirst Posted
Study publicly available on registry
February 1, 2012
CompletedStudy Start
First participant enrolled
March 1, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 1, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
July 1, 2016
CompletedOctober 4, 2016
October 1, 2016
4.3 years
January 25, 2012
October 3, 2016
Conditions
Outcome Measures
Primary Outcomes (1)
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 Outcomes (2)
NY-ESO-1 specific cellular immunity
Up to 12 months post-treatment
NY-ESO-1 specific humoral immunity
Up to 12 months post-treatment
Other Outcomes (1)
Time to disease progression
Up to 12 months post treatment
Study Arms (5)
Cohort 1a (vaccine therapy)
EXPERIMENTALPatients receive DEC-205/NY-ESO-1 fusion protein CDX-1401 protein vaccine intranodally on days 1, 29, 57, and 113.
Cohort 1b (vaccine therapy and immunotherapy)
EXPERIMENTALPatients 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.
Cohort 1c (vaccine therapy and immunotherapy)
EXPERIMENTALPatients 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.
Cohort 1d (vaccine therapy and immunotherapy)
EXPERIMENTALPatients 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 (vaccine therapy with or without immunotherapy)
EXPERIMENTALPatients 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.
Interventions
Given intranodally
Correlative studies
Correlative studies
Given PO or PEG
Eligibility Criteria
You may qualify if:
- 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
- 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
- +17 more criteria
You may not qualify if:
- 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
- +1 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Roswell Park Cancer Institutelead
- National Cancer Institute (NCI)collaborator
Study Sites (1)
Roswell Park Cancer Institute
Buffalo, New York, 14263, United States
Related Publications (1)
Withers HG, Matsuzaki J, Long M, Rosario SR, Chodon T, Tsuji T, Koya R, Yan L, Wang J, Keler T, Lele SB, Zsiros E, Lugade A, Hutson A, Blank S, Bhardwaj N, Shrikant P, Liu S, Odunsi K. mTOR inhibition modulates vaccine-induced immune responses to generate memory T cells in patients with solid tumors. J Immunother Cancer. 2025 Mar 25;13(3):e010408. doi: 10.1136/jitc-2024-010408.
PMID: 40132910DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Kunle Odunsi
Roswell Park Cancer Institute
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 25, 2012
First Posted
February 1, 2012
Study Start
March 1, 2012
Primary Completion
July 1, 2016
Study Completion
July 1, 2016
Last Updated
October 4, 2016
Record last verified: 2016-10