A Phase 2 Study of the IDO Inhibitor Epacadostat Versus Tamoxifen for Subjects With Biochemical-recurrent-only EOC, PPC or FTC Following Complete Remission With First-line Chemotherapy

Study Overview
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Brief Summary
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This is an open-label, randomized, phase 2 study of an IDO inhibitor, INCB024360 (epacadostat) versus tamoxifen in biochemical recurrent only ovarian cancer patients following complete remission with first-line chemotherapy.

Official Title
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A Randomized, Open-Label, Phase 2 Study of the IDO Inhibitor Epacadostat Versus Tamoxifen for Subjects With Biochemical-Recurrent-Only Epithelial Ovarian Cancer, Primary Peritoneal Carcinoma, or Fallopian Tube Cancer Following Complete Remission With First-Line Chemotherapy

Conditions
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Ovarian Cancer, Genitourinary (GU) Tumors

Intervention / Treatment
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* Drug: Epacadostat
* Drug: tamoxifen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who have received first-line chemotherapy, which must have been a platinum-containing regimen. Subjects who received maintenance paclitaxel or, bevacizumab, or alternative maintenance therapy (e.g. vaccines) are eligible for enrollment provided they have discontinued therapy at least 4 weeks for prior taxane and, at least 8 weeks for bevacizumab, or received medical monitor approval for time lapse from alternative maintenance therapy prior to randomization and recovered from toxicities to less than Grade 2. Subject must be currently in remission by clinical and radiological criteria (Response Evaluation Criteria for Solid Tumors [RECIST 1.1]). a. If a PET scan or high-resolution CT scan is performed and demonstrates new disease </= 1 cm, these subjects would be eligible. Clinical remission is defined as: asymptomatic and a negative physical examination. Scans are required post completion of platinum-containing therapy to document disease remission. Prior to the first-line regimen, CA 125 must have been elevated at first diagnosis, must have normalized with the first-line therapy/regimen, and is currently elevated: a. CA 125 elevation is defined as 2 consecutive measurements that are both above the Upper Limit of Normal (ULN) at least 42 weeks apart, with the second measure showing further increases from the first measurement If CA 125 is ≥ 2 × ULN the confirmatory value only needs to be 1 week apart. CA 125 elevation is defined as a value that is at least 2 × ULN on 2 occasions at least 1 week apart (UK ONLY REQUIREMENT). CA 125 elevation must be at least 3 months from completion of first-line platinum-containing regimen. Documentation of at least 1 normal CA 125 level at approximately 3 months during or following first line therapy is required. Subjects must have available archived tumor tissue. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Adequate renal, hepatic, and bone marrow function based on screening laboratory assessments. Exclusion Criteria: Subjects with any evidence of new disease (> 1 cm) including new ascites as confirmed by imaging. Any other prior antitumor systemic therapy except for first-line chemotherapy associated with previous CA 125 normalization or maintenance paclitaxel, bevacizumab, or alternative maintenance therapy as approved by the medical monitor. Subjects with prior radiotherapy within 3 months of randomization and have not recovered from all radiotherapy-related toxicities, who have received radiation therapy to the chest within 3 months of randomization, or who have a history or radiation pneumonitis. Subjects with protocol-specified active autoimmune processes except vitiligo or thyroiditis. Subjects receiving investigational study drug for any indication, immunological-based treatment for any reason (except completed adjuvant therapy with medical monitor approval), or potent CYP3A4 inducers or inhibitors. Subjects receiving monoamine oxidase inhibitors (MAOIs) within the 21 days prior to screening; subjects who have ever had Serotonin Syndrome (SS) after receiving 1 or more serotonergic drugs. Subjects for whom tamoxifen therapy is contraindicated.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Epacadostat<br>Subjects randomized to Arm A (epacadostat) will take epacadostat tablets at a dose of 600 mg BID, beginning on Day 1. | Drug: Epacadostat<br> <br> * Other names: INCB024360;|
| Active Comparator: Tamoxifen<br>Subjects randomized to Arm B (tamoxifen) will take tamoxifen tablets at a dose of 20 mg BID, beginning on Day 1. | Drug: tamoxifen<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival (PFS) using Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 definition of progression as determined by the investigator. |  | PFS is defined as the number of days from randomization to the earlier of death or disease progression for up to 36 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of epacadostat by adverse event assessment. |  | Adverse events assessed every 2 weeks during cycle 1, then every 28 days thereafter until each subject's death or disease progression or for up to 36 months, whichever is longest. | 
| Cancer Antigen (CA) 125 response rate, using Gynaecologic Cancer Intergroup (GCIG) criteria. |  | CA 125 response rate defined as at least 50% reduction on study as compared to pretreatment sample; pre-treatment sample must be at least 2x ULN and response must be sustained for at least 28 days. | 
| Duration of overall survival. |  | Overall survival followed every 12 weeks until last date known to be alive, until subjects withdraw consent or up to 36 months, whichever is longest. | 
| Progression-free survival using RECIST 1.1 definition of objective progression as determined by the central imaging laboratory. |  | Progression free survival defined by central imaging lab using RECIST 1.1 assessed at 8 week intervals, retrospectively, until disease progression, death, subject withdraw of consent or up to 36 months, whichever is longest. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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FIGO Stage III or IV EOC, PPC FTC, increasing CA 125