Vaccine Therapy and IDO1 Inhibitor INCB024360 in Treating Patients With Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Who Are in Remission

This study has been withdrawn prior to enrollment.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Roswell Park Cancer Institute
ClinicalTrials.gov Identifier:
NCT01982487
First received: November 6, 2013
Last updated: December 17, 2013
Last verified: December 2013
  Purpose

This partially randomized phase I/IIb trial studies the side effects vaccine therapy and indoleamine 2,3-dioxygenase (IDO1) inhibitor 4-amino-1,2,5-oxadizaole-3-carboximidamide (INCB024360) and to see how well they work in treating patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in remission. Vaccines made from gene-modified virus may help the body build an effective immune response to kill tumor cells. IDO1 inhibitor INCB024360 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving vaccine therapy with IDO1 inhibitor INCB024360 may be an effective treatment for epithelial ovarian, fallopian tube, or primary peritoneal cancer.


Condition Intervention Phase
Recurrent Fallopian Tube Cancer
Recurrent Ovarian Epithelial Cancer
Recurrent Primary Peritoneal Cavity Cancer
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: ALVAC(2)-NY-ESO-1 (M)/TRICOM vaccine
Drug: IDO1 inhibitor INCB024360
Other: laboratory biomarker analysis
Other: pharmacological study
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/IIb Study of Recombinant ALVAC(2)-NY-ESO-1 (M)/TRICOM 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:
  • Maximum tolerated dose of IDO1 inhibitor INCB024360, determined by incidence of dose limiting toxicities graded according to the NCI CTCAE version 4.0 (Phase I) [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
  • PFS (Phase IIb) [ Time Frame: Up to 15 years ] [ Designated as safety issue: No ]
    The primary analysis will be carried forth using a Cox proportional hazards model with factors corresponding to treatment combination, IDO1 inhibitor INCB024360 (yes/no) and ALVAC(2)-NY-ESO-1 (M)/TRICOM vaccine (yes/no), a continuous covariate adjustment for the length of the treatment free interval and a blocking factor.


Secondary Outcome Measures:
  • Immunological response [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]
    Immunological parameters (antibody titres, NY-ESO-1 specific CD8+ and CD4+ frequency and function, frequency of memory T cell populations, TCR avidity, secondary recall response) will be analyzed in a straightforward analysis-of-covariance (ANCOVA) fashion modeling post-treatment levels as a function of pre-treatment levels with factors corresponding to IDO1 inhibitor INCB024360 (yes/no) and ALVAC(2)-NY-ESO-1 (M)/TRICOM vaccine (yes/no).

  • Toxicity rate, graded 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.


Enrollment: 0
Study Start Date: December 2013
Estimated Primary Completion Date: September 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: Arm A (no treatment)
Patients receive no treatment.
Experimental: Arm B (IDO1 inhibitor INCB024360)
Patients receive IDO1 inhibitor INCB024360 PO BID on days 1-28.
Drug: IDO1 inhibitor INCB024360
Given PO
Other Names:
  • INCB024360
  • indoleamine-2,3-dioxygenase inhibitor INCB024360
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Experimental: Arm C (vaccine, IDO1 inhibitor INCB024360)
Patients receive ALVAC(2)-NY-ESO-1 (M)/TRICOM vaccine SC on day 1 and IDO1 inhibitor INCB024360 PO BID on days 1-28.
Biological: ALVAC(2)-NY-ESO-1 (M)/TRICOM vaccine
Given SC
Other Name: vCP2292
Drug: IDO1 inhibitor INCB024360
Given PO
Other Names:
  • INCB024360
  • indoleamine-2,3-dioxygenase inhibitor INCB024360
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Experimental: Arm D (vaccine)
Patients receive ALVAC(2)-NY-ESO-1 (M)/TRICOM vaccine SC on day 1.
Biological: ALVAC(2)-NY-ESO-1 (M)/TRICOM vaccine
Given SC
Other Name: vCP2292
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the safety of fixed doses of the modified canarypox vector (ALVAC[2])-cancer/testis antigen 1B (NY-ESO-1) (M)/triad of costimulatory molecules (TRICOM) 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) 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 NY-ESO-1 specific cellular and humoral immunity in peripheral blood NY-ESO-1 specific CD8+ and CD4+ T cells.

II. To determine the effectiveness of INCB024360 on enhancing vaccine efficacy by assessing NY-ESO-1 specific cellular and humoral immunity in peripheral blood NY-ESO-1 specific antibodies.

III. To determine the effectiveness of INCB024360 on enhancing vaccine efficacy by assessing NY-ESO-1 specific cellular and humoral immunity in peripheral blood frequency of CD4+CD25+FOXP3+ regulatory T cells.

IV. To determine the effectiveness of INCB024360 on enhancing vaccine efficacy by assessing NY-ESO-1 specific cellular and humoral immunity in pharmacokinetics (PK) of IDO in relation to T cell frequency and function in correlation with PFS.

OUTLINE: This is a Phase I study followed by a randomized Phase IIb study.

PHASE I: Patients receive ALVAC(2)-NY-ESO-1 (M)/TRICOM vaccine subcutaneously (SC) on day 1 and IDO1 inhibitor INCB024360 orally (PO) twice daily (BID) on days 1-28. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

PHASE IIb: Patients are randomized to 1 of 4 arms.

ARM A: Patients receive no treatment.

ARM B: Patients receive IDO1 inhibitor INCB024360 PO BID on days 1-28.

ARM C: Patients receive ALVAC(2)-NY-ESO-1 (M)/TRICOM vaccine SC on day 1 and IDO1 inhibitor INCB024360 PO BID on days 1-28.

ARM D: Patients receive ALVAC(2)-NY-ESO-1 (M)/TRICOM vaccine SC on day 1.

In all arms, treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 6 weeks; at 3, 6, and 12 months; and then annually for up to 15 years.

  Eligibility

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

Inclusion Criteria:

  • Women with epithelial ovarian, fallopian tube, or primary peritoneal carcinoma and 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 cancer/testis antigen 2 (LAGE-1) by immunohistochemistry (IHC) and/or reverse transcription-polymerase chain reaction (RTPCR)
  • No allergy to eggs
  • Life expectancy > 6 months
  • Hematology and biochemistry laboratory results within the limits normally expected for the patient population, without evidence of major organ failure
  • Absolute neutrophil count (ANC) >= 1,000/uL
  • Platelet count (PLT) >= 75,000/uL
  • Hemoglobin (Hgb) >= 8g/dL
  • Total bilirubin =< 1.5 x upper limit of normal (ULN)
  • Serum aspartate aminotransferase (serum glutamic oxalacetic 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
  • 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) 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 autoimmune disease (e.g. thyroiditis, lupus) except vitiligo
  • Concomitant systemic treatment with 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
  • Clinically significant heart disease (New York Heart Association [NYHA] class III or class IV) within 6 months
  • 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 judgement, 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: NCT01982487

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: NCT01982487     History of Changes
Other Study ID Numbers: I 243013, NCI-2013-02080, 080913, SRC1 082013, IRB 100313, SRC2 082713, I 243013, P30CA016056
Study First Received: November 6, 2013
Last Updated: December 17, 2013
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Peritoneal Neoplasms
Fallopian Tube Neoplasms
Neoplasms, Glandular and Epithelial
Ovarian Neoplasms
Abdominal Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Peritoneal Diseases
Genital Neoplasms, Female
Urogenital Neoplasms
Fallopian Tube Diseases
Adnexal Diseases
Genital Diseases, Female
Neoplasms by Histologic Type
Endocrine Gland Neoplasms
Ovarian Diseases
Endocrine System Diseases
Gonadal Disorders

ClinicalTrials.gov processed this record on September 16, 2014