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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Given SC
Given PO
Correlative studies
Correlative studies
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
PFS (Phase IIb)
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.
Time frame: Up to 15 years
Immunological response
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).
Time frame: Up to 12 months
Toxicity rate, graded according to NCI CTCAE version 4.0
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.
Time frame: Up to 12 months
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.