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Trial record 3 of 129 for:    1401

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Roswell Park Cancer Institute
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Roswell Park Cancer Institute
ClinicalTrials.gov Identifier:
NCT02166905
First received: April 21, 2014
Last updated: September 30, 2014
Last verified: September 2014
  Purpose

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.


Condition Intervention Phase
Stage IA Fallopian Tube Cancer
Stage IA Ovarian Epithelial Cancer
Stage IA Primary Peritoneal Cavity Cancer
Stage IB Fallopian Tube Cancer
Stage IB Ovarian Epithelial Cancer
Stage IB Primary Peritoneal Cavity Cancer
Stage IC Fallopian Tube Cancer
Stage IC Ovarian Epithelial Cancer
Stage IC Primary Peritoneal Cavity Cancer
Stage IIA Fallopian Tube Cancer
Stage IIA Ovarian Epithelial Cancer
Stage IIA Primary Peritoneal Cavity Cancer
Stage IIB Fallopian Tube Cancer
Stage IIB Ovarian Epithelial Cancer
Stage IIB Primary Peritoneal Cavity Cancer
Stage IIC Fallopian Tube Cancer
Stage IIC Ovarian Epithelial Cancer
Stage IIC Primary Peritoneal Cavity Cancer
Stage IIIA Fallopian Tube Cancer
Stage IIIA Ovarian Epithelial Cancer
Stage IIIA Primary Peritoneal Cavity Cancer
Stage IIIB Fallopian Tube Cancer
Stage IIIB Ovarian Epithelial Cancer
Stage IIIB Primary Peritoneal Cavity Cancer
Stage IIIC Fallopian Tube Cancer
Stage IIIC Ovarian Epithelial Cancer
Stage IIIC Primary Peritoneal Cavity Cancer
Stage IV Fallopian Tube Cancer
Stage IV Ovarian Epithelial Cancer
Stage IV Primary Peritoneal Cavity Cancer
Biological: DEC-205/NY-ESO-1 fusion protein CDX-1401
Drug: poly ICLC
Drug: IDO1 inhibitor INCB024360
Other: pharmacological study
Other: laboratory biomarker analysis
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Roswell Park Cancer Institute:

Primary Outcome Measures:
  • MTD determined by the incidence of dose limiting toxicities graded according to NCI CTCAE version 4.0 (Phase I) [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
  • Progression free survival using RECIST 1.1 (Phase II) [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]
    Analyzed using a Cox proportional hazards model.


Secondary Outcome Measures:
  • Incidence of toxicity assessed according to NCI CTCAE version 4.0 [ Time Frame: Up to 12 months ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 98
Study Start Date: August 2014
Estimated Primary Completion Date: February 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: Arm I (standard of care)
Patients receive no intervention (standard of care).
Experimental: Arm II (IDO1 inhibitor INCB024360)
Patients receive IDO1 inhibitor INCB024360 as in Phase I.
Drug: IDO1 inhibitor INCB024360
Given PO
Other Names:
  • INCB024360
  • indoleamine-2,3-dioxygenase inhibitor INCB024360
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies
Experimental: Arm III (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.
Biological: DEC-205/NY-ESO-1 fusion protein CDX-1401
Given via intracutaneous injection
Other Name: CDX-1401
Drug: poly ICLC
Given SC
Other Names:
  • Hiltonol
  • poly I:poly C with poly-1-lysine stabilizer
  • Polyinosinic-Polycytidylic Acid Stabilized with Polylysine and Carboxymethylcellulose
  • stabilized polyriboinosinic/polyribocytidylic acid
Drug: IDO1 inhibitor INCB024360
Given PO
Other Names:
  • INCB024360
  • indoleamine-2,3-dioxygenase inhibitor INCB024360
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies
Experimental: Arm IV (CDX-1401, poly ICLC)
Patients receive DEC-205/NY-ESO-1 fusion protein CDX-1401 and poly ICLC as in Phase I.
Biological: DEC-205/NY-ESO-1 fusion protein CDX-1401
Given via intracutaneous injection
Other Name: CDX-1401
Drug: poly ICLC
Given SC
Other Names:
  • Hiltonol
  • poly I:poly C with poly-1-lysine stabilizer
  • Polyinosinic-Polycytidylic Acid Stabilized with Polylysine and Carboxymethylcellulose
  • stabilized polyriboinosinic/polyribocytidylic acid
Other: laboratory biomarker analysis
Correlative studies

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 imaging response (Response Evaluation Criteria in Solid Tumors [RECIST] 1.1) 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. Peripheral blood NY-ESO-1 specific cluster of differentiation (CD)8+ and CD4+ T cells.

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

V. 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 4 treatment arms.

ARM I: No intervention (standard of care).

ARM II: Patients receive IDO1 inhibitor INCB024360 as in Phase I.

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

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

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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Eligible patients will be women with epithelial ovarian, fallopian tube, or primary peritoneal carcinoma with no evidence of disease or no measurable disease after 1st or 2nd line therapy; 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 transcription 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
  • Prothrombin time (PT)/international normalized ratio (INR) =< 1.5
  • 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
  • Use of UDP glucuronosyltransferase 1 family, polypeptide A9 (UGT1A9) inhibitor including: diclofenac, imipramine, ketoconazole, mefenamic acid, and probenecid
  • 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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02166905

Locations
United States, New York
Roswell Park Cancer Institute Recruiting
Buffalo, New York, United States, 14263
Contact: Roswell Park    877-275-7724    ASKRPCI@RoswellPark.org   
Principal Investigator: Kunle Odunsi         
Sponsors and Collaborators
Roswell Park Cancer Institute
Investigators
Principal Investigator: Kunle Odunsi Roswell Park Cancer Institute
  More Information

No publications provided

Responsible Party: Roswell Park Cancer Institute
ClinicalTrials.gov Identifier: NCT02166905     History of Changes
Other Study ID Numbers: I 248613, NCI-2014-00771, I 248613, P30CA016056
Study First Received: April 21, 2014
Last Updated: September 30, 2014
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Fallopian Tube Neoplasms
Neoplasms, Glandular and Epithelial
Ovarian Neoplasms
Peritoneal Neoplasms
Abdominal Neoplasms
Adnexal Diseases
Digestive System Diseases
Digestive System Neoplasms
Endocrine Gland Neoplasms
Endocrine System Diseases
Fallopian Tube Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Gonadal Disorders
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Ovarian Diseases
Peritoneal Diseases
Urogenital Neoplasms
Carboxymethylcellulose Sodium
Poly I-C
Poly ICLC
Anti-Infective Agents
Antiviral Agents
Gastrointestinal Agents
Immunologic Factors
Interferon Inducers
Laxatives
Pharmacologic Actions

ClinicalTrials.gov processed this record on November 20, 2014