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Anaplastic AstrocytomaPhase 1NCT01522820

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

A Phase 1 study testing DEC-205/NY-ESO-1 Fusion Protein CDX-1401, Laboratory Biomarker Analysis and Pharmacological Study in people with Anaplastic Astrocytoma and Anaplastic Oligoastrocytoma, run by Roswell Park Cancer Institute at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
DEC-205/NY-ESO-1 Fusion Protein CDX-1401, Laboratory Biomarker Analysis and Pharmacological Study
Type of treatment
Vaccines
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
1 siteUnited States
Study dates
Mar 2012to Jul 2016
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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)

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

Other trials in United States

About this study

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

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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:

  1. 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.

Being tested
DEC-205/NY-ESO-1 Fusion Protein CDX-1401, Laboratory Biomarker Analysis, Pharmacological Study, Sirolimus
Medical subject headings
Astrocytoma, Oligodendroglioma, Glioblastoma, Prostatic Neoplasms, Carcinoma, Renal Cell, Brain Neoplasms, Urinary Bladder Neoplasms, Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DEC-205/NY-ESO-1 Fusion Protein CDX-1401Biological

    Also called CDX-1401

    Given intranodally

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Pharmacological StudyOther

    Correlative studies

  • SirolimusDrug

    Also called AY 22989, RAPA, Rapamune, RAPAMYCIN

    Given PO or PEG

Study groups in NCT01522820
Study groupRoleWhat they receive
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.
Receives: Biological: DEC-205/NY-ESO-1 Fusion Protein CDX-1401; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study
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.
Receives: Biological: DEC-205/NY-ESO-1 Fusion Protein CDX-1401; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Sirolimus
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.
Receives: Biological: DEC-205/NY-ESO-1 Fusion Protein CDX-1401; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Sirolimus
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.
Receives: Biological: DEC-205/NY-ESO-1 Fusion Protein CDX-1401; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Sirolimus
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.
Receives: Biological: DEC-205/NY-ESO-1 Fusion Protein CDX-1401; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Sirolimus

What is being measured

The primary outcome is the main question the study is designed to answer.

  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).

    Measured: Up to 12 months post-treatment

Secondary outcomes (2)

  1. 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.

    Measured: Up to 12 months post-treatment

  2. 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.

    Measured: Up to 12 months post-treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Feb 2012 (estimated)
  2. Study startMar 2012
  3. Primary completionJul 2016
  4. Study completionJul 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
18 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01522820
Sponsor's protocol ID
I 191511
Other IDs
NCI-2011-03568, 071614, I 191511, P30CA016056, R01CA158318
Status last verified
Oct 2016
First submitted
25 Jan 2012
Last updated
4 Oct 2016
Results posted
No
Data monitoring committee
No

Publications

  • 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.

    PubMed 40132910

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing DEC-205/NY-ESO-1 Fusion Protein CDX-1401, Laboratory Biomarker Analysis and Pharmacological Study in people with Anaplastic Astrocytoma and Anaplastic Oligoastrocytoma, run by Roswell Park Cancer Institute at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 33 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Oct 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 (time frame: Up to 12 months post-treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01522820, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Oct 2016.

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