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DEC-205/NY-ESO-1 Fusion Protein CDX-1401, Poly ICLC, and IDO1 Inhibitor INCB024360 in Treating Patients With Ovarian, Fallopian Tube, or Primary Peritoneal Cancer in Remission

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ClinicalTrials.gov Identifier: NCT02166905
Recruitment Status : Active, not recruiting
First Posted : June 18, 2014
Last Update Posted : May 14, 2020
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Celldex Therapeutics
Incyte Corporation
Information provided by (Responsible Party):
Roswell Park Cancer Institute

Tracking Information
First Submitted Date  ICMJE April 21, 2014
First Posted Date  ICMJE June 18, 2014
Last Update Posted Date May 14, 2020
Study Start Date  ICMJE August 1, 2014
Estimated Primary Completion Date February 12, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 22, 2016)
  • Maximum tolerated dose determined by the incidence of dose limiting toxicities graded according to NCI CTCAE version 4.0 (Phase I) [ Time Frame: 28 days ]
  • Progression free survival using standard irRC (Phase II) [ Time Frame: Up to 12 months ]
    Analyzed using a Cox proportional hazards model.
Original Primary Outcome Measures  ICMJE
 (submitted: June 16, 2014)
  • MTD of determined by the incidence of dose limiting toxicities graded according to NCI CTCAE version 4.0 (Phase I) [ Time Frame: 28 days ]
  • Progression free survival (Phase II) [ Time Frame: Up to 12 months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 22, 2016)
  • Antibody titers [ Time Frame: Up to 12 months ]
    Antibody titers will be analyzed via an analysis-of-covariance (ANCOVA) model with post-treatment levels modeled as a function pre-treatment levels and main effects to the parallel design.
  • Frequency of memory T cell populations [ Time Frame: Up to 12 months ]
    The frequency of memory T cell population will be analyzed via an ANCOVA model with post-treatment levels modeled as a function pre-treatment levels and main effects to the parallel design.
  • Incidence of toxicity assessed according to NCI CTCAE version 4.0 [ Time Frame: Up to 12 months ]
    The toxicity rate will be estimated using a one-sided, 95%, exact binomial confidence interval (Clopper-Pearson). The lower one sided limit will be used.
  • NY-ESO-1 specific CD8+ and CD4+ frequency and function [ Time Frame: Up to 12 months ]
    NY-ESO-1 specific CD8+ and CD4+ frequency and function will be analyzed via an ANCOVA model with post-treatment levels modeled as a function pre-treatment levels and main effects to the parallel design.
  • T cell receptor (TCR) avidity [ Time Frame: Up to 12 months ]
    TCR avidity will be analyzed via an ANCOVA model with post-treatment levels modeled as a function pre-treatment levels and main effects to the parallel design.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 16, 2014)
  • Incidence of toxicity assessed according to NCI CTCAE version 4.0 [ Time Frame: Up to 12 months ]
    The toxicity rate will be estimated using a one-sided, 95%, exact binomial confidence interval (Clopper-Pearson). The lower one sided limit will be used.
  • Antibody titers [ Time Frame: Up to 12 months ]
    Antibody titers will be analyzed via an analysis-of-covariance (ANCOVA) model with post-treatment levels modeled as a function pre-treatment levels and main effects corresponding to the 3 x 3 design.
  • NY-ESO-1 specific CD8+ and CD4+ frequency and function [ Time Frame: Up to 12 months ]
    NY-ESO-1 specific CD8+ and CD4+ frequency and function will be analyzed via an ANCOVA model with post-treatment levels modeled as a function pre-treatment levels and main effects corresponding to the 3 x 3 design.
  • Frequency of memory T cell populations [ Time Frame: Up to 12 months ]
    The frequency of memory T cell population will be analyzed via an ANCOVA model with post-treatment levels modeled as a function pre-treatment levels and main effects corresponding to the 3 x 3 design.
  • T cell receptor (TCR) avidity [ Time Frame: Up to 12 months ]
    TCR avidity will be analyzed via an ANCOVA model with post-treatment levels modeled as a function pre-treatment levels and main effects corresponding to the 3 x 3 design.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE DEC-205/NY-ESO-1 Fusion Protein CDX-1401, Poly ICLC, and IDO1 Inhibitor INCB024360 in Treating Patients With Ovarian, Fallopian Tube, or Primary Peritoneal Cancer in Remission
Official Title  ICMJE A Phase I/IIb Study of DEC205mAb-NY-ESO-1 Fusion Protein (CDX-1401) Given With Adjuvant Poly-ICLC in Combination With INCB024360 for Patients in Remission With Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Carcinoma Whose Tumors Express NY-ESO-1 or LAGE-1 Antigen
Brief Summary This partially randomized phase I/IIb trial studies the side effects and best dose of IDO1 inhibitor INCB024360 in combination with DEC-205/NY-ESO-1 fusion protein CDX-1401 and poly ICLC and to see how well they work in treating patients with ovarian, fallopian tube, or primary peritoneal cancer who no longer have evidence of disease. Antigens (such as cancer/testis antigen [NY-ESO-1] protein) are found on many cancer cells. Vaccines made from NY-ESO-1 protein may cause the immune system to produce immune cells and antibodies that may help locate the NY-ESO-1 and/or cancer/testis antigen 2 (LAGE-1) antigens on cancer cells. By finding them, the immune system may then work to control or eliminate the remaining cancer cells. INCB024360 is an inhibitor of an enzyme called indoleamine 2,3 dioxygenase (IDO). This enzyme is produced by tumor cells to disable immune cells, and limit the efficacy of immune attack. Giving DEC-205/NY-ESO-1 fusion protein CDX-1401 with poly ICLC and IDO1 inhibitor INCB024360 may generate stronger and more long lasting anti-cancer immune responses in patients with ovarian, fallopian tube, and primary peritoneal cancer in remission.
Detailed Description

PRIMARY OBJECTIVES:

I. To determine the safety of fixed doses of DEC205mAb-NY-ESO-1 fusion protein (DEC-205/NY-ESO-1 fusion protein CDX-1401) with adjuvant poly-ICLC given as a vaccine in combination with INCB024360 (IDO1 inhibitor INCB024360). (Phase I) II. To evaluate toxicity as defined by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. (Phase I) III. To determine the progression free survival (PFS) (primary endpoint) using standard immune-related response criteria (irRC) criteria. (Phase IIb)

SECONDARY OBJECTIVES:

I. To determine the effectiveness of INCB024360 on enhancing vaccine efficacy by assessing cancer-testis antigen (NY-ESO-1) specific cellular and humoral immunity.

II. To determine the effectiveness of Sirolimus on enhancing vaccine efficacy by assessing NY-ESO-1 specific cellular and humoral immunity (Exploratory Cohort ONLY) III. Peripheral blood NY-ESO-1 specific cluster of differentiation (CD)8+ and CD4+ T cells.

IV. Peripheral blood NY-ESO-1 specific antibodies. V. Peripheral blood frequency of CD4+CD25+forkhead box P3 (FOXP3)+ regulatory T cells.

VI. Pharmacokinetics of INCB02360 in relation to T cell frequency and function in correlation with PFS.

OUTLINE:

PHASE I:

Patients receive DEC-205/NY-ESO-1 fusion protein CDX-1401 via intracutaneous injection on day 1, poly ICLC subcutaneously (SC) on days 1 and 2, and IDO1 inhibitor INCB024360 orally (PO) twice daily (BID) on days 1-28. Treatment repeats every 28 days for up to 5 courses in the absence of disease progression or unacceptable toxicity. Patients receive IDO1 inhibitor INCB024360 for up to 7 courses.

PHASE IIb: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive DEC-205/NY-ESO-1 fusion protein CDX-1401 and poly ICLC as in Phase I.

ARM II: Patients receive DEC-205/NY-ESO-1 fusion protein CDX-1401, poly ICLC, and IDO1 inhibitor INCB024360 as in Phase I.

After completion of study treatment, patients are followed up for 30 days and then at 3, 6, and 12 months.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Fallopian Tube Carcinoma
  • Ovarian Carcinoma
  • Primary Peritoneal Carcinoma
Intervention  ICMJE
  • Biological: DEC-205/NY-ESO-1 Fusion Protein CDX-1401
    Given via intracutaneous injection
    Other Name: CDX-1401
  • Drug: Epacadostat
    Given PO
    Other Names:
    • INCB 024360
    • INCB024360
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Other: Pharmacological Study
    Correlative studies
  • Drug: Poly ICLC
    Given SC
    Other Names:
    • Hiltonol
    • Poly I:Poly C with Poly-L-Lysine Stabilizer
    • poly-ICLC
    • PolyI:PolyC with Poly-L-Lysine Stabilizer
    • Polyinosinic-Polycytidylic Acid Stabilized with Polylysine and Carboxymethylcellulose
    • Polyriboinosinic-Polyribocytidylic Acid-Polylysine Carboxymethylcellulose
    • Stabilized Polyriboinosinic/Polyribocytidylic Acid
Study Arms  ICMJE
  • Experimental: Arm I (CDX-1401, poly ICLC)
    Patients receive DEC-205/NY-ESO-1 fusion protein CDX-1401 and poly ICLC as in Phase I.
    Interventions:
    • Biological: DEC-205/NY-ESO-1 Fusion Protein CDX-1401
    • Other: Laboratory Biomarker Analysis
    • Other: Pharmacological Study
    • Drug: Poly ICLC
  • Experimental: Arm II (CDX-1401, poly ICLC, IDO1 inhibitor INCB024360)
    Patients receive DEC-205/NY-ESO-1 fusion protein CDX-1401, poly ICLC, and IDO1 inhibitor INCB024360 as in Phase I.
    Interventions:
    • Biological: DEC-205/NY-ESO-1 Fusion Protein CDX-1401
    • Drug: Epacadostat
    • Other: Laboratory Biomarker Analysis
    • Other: Pharmacological Study
    • Drug: Poly ICLC
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: May 13, 2020)
40
Original Estimated Enrollment  ICMJE
 (submitted: June 16, 2014)
98
Estimated Study Completion Date  ICMJE February 12, 2023
Estimated Primary Completion Date February 12, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Eligible patients will be women with epithelial ovarian, fallopian tube, or primary peritoneal carcinoma after chemotherapy with no evidence of disease or minimal residual disease for primary or recurrent disease; this may or may not be measurable; these patients would normally enter a period of observation after standard management
  • 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 transcriptase polymerase chain reaction (RTPCR)
  • Life expectancy > 6 months
  • Absolute neutrophil count (ANC) >= 1,000/uL
  • Platelets (PLT) >= 100,000/uL
  • Hemoglobin (Hgb) >= 8 g/dL
  • Total bilirubin =< 1.5 x upper limit of normal (ULN)
  • Serum aspartate aminotransferase (serum glutamic oxaloacetic transaminase [SGOT]/AST) or serum alanine aminotransferase (serum glutamate pyruvate transaminase [SGPT]/ALT) =< 3 x ULN
  • Serum creatinine =< 2 x ULN
  • 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
  • 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
  • Patients may have received previous NY-ESO-1 vaccine therapy; patients who received maintenance paclitaxel or bevacizumab are eligible for enrollment provided they have discontinued therapy (at least 4 weeks for prior taxane or prior bevacizumab) prior to randomization and recovered from toxicities to less than grade 2

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 chronic use (based on the investigator's judgment) of corticosteroids, anti-histamine or non-steroidal anti-inflammatory drugs, and other platelet inhibitory agents
  • Chemotherapy, radiation therapy, or immunotherapy within 4 weeks prior to first dosing of study drug (6 weeks for nitrosoureas); concomitant hormonal therapies for breast cancers are allowed
  • Subjects being treated with a monoamine oxidase inhibitor (MAOI), or drug which has significant MAOI activity (e.g., Meperidine, linezolid, methylene blue) within 3 weeks prior to screening
  • Subjects who are currently receiving therapy with a potent cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inducer or inhibitor (e.g. clarithromycin, telithromycin, nefazodone, itraconazole, ketoconazole, atazanavir)
  • Use of UDP glucuronosyltransferase 1 family, polypeptide A9 (UGT1A9) inhibitor including: diclofenac, imipramine, and ketoconazole
  • Participation in any other clinical trial involving another investigational agent within 4 weeks prior to first dosing of study drug
  • Known hepatitis B, hepatitis C, or human immunodeficiency virus (HIV)
  • 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
  • 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 patient's risk by participating in this study)
  • Known hypersensitivity to any of the study drugs that will be given to the participant
  • Additional exclusion criteria for exploratory cohort ONLY: Known pulmonary hypertension
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02166905
Other Study ID Numbers  ICMJE I 248613
NCI-2014-00771 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
I 248613 ( Other Identifier: Roswell Park Cancer Institute )
P30CA016056 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Roswell Park Cancer Institute
Study Sponsor  ICMJE Roswell Park Cancer Institute
Collaborators  ICMJE
  • National Cancer Institute (NCI)
  • Celldex Therapeutics
  • Incyte Corporation
Investigators  ICMJE
Principal Investigator: Kunle Odunsi Roswell Park Cancer Institute
PRS Account Roswell Park Cancer Institute
Verification Date May 2020

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