Clinical trial NCT01685255: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Ovarian Cancer
Genitourinary (GU) Tumors
Keywords: FIGO Stage III or IV EOC
PPC FTC
increasing CA 125
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2012-09-14
Enrollment: 83
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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
  1. If CA 125 is ≥ 2 × ULN the confirmatory value only needs to be 1 week apart.
  2. 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.

Primary outcomes:
measure: Progression free survival (PFS) using Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 definition of progression as determined by the investigator.
timeFrame: PFS is defined as the number of days from randomization to the earlier of death or disease progression for up to 36 months.
Secondary outcomes:
measure: Safety and tolerability of epacadostat by adverse event assessment.
timeFrame: 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.
measure: Cancer Antigen (CA) 125 response rate, using Gynaecologic Cancer Intergroup (GCIG) criteria.
timeFrame: 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.
measure: Duration of overall survival.
timeFrame: 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.
measure: Progression-free survival using RECIST 1.1 definition of objective progression as determined by the central imaging laboratory.
timeFrame: 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.
Other outcomes:
Locations:
city: La Jolla
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: San Francisco
country: United States
state: California
city: Evanston
country: United States
state: Illinois
city: Joliet
country: United States
state: Illinois
city: Iowa City
country: United States
state: Iowa
city: Covington
country: United States
state: Louisiana
city: Baltimore
country: United States
state: Maryland
city: Detroit
country: United States
state: Michigan
city: Minneapolis
country: United States
state: Minnesota
city: Bridgewater
country: United States
state: New York
city: Buffalo
country: United States
state: New York
city: Mineola
country: United States
state: New York
city: Durham
country: United States
state: North Carolina
city: Abington
country: United States
state: Pennsylvania
city: Philadelphia
country: United States
state: Pennsylvania
city: Greenville
country: United States
state: South Carolina
city: Bendigo
country: Australia
city: Heidelberg
country: Australia
city: Herston
country: Australia
city: Milton
country: Australia
city: Randwick
country: Australia
city: Calgary
country: Canada
state: Alberta
city: Toronto
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Ekaterinburg
country: Russian Federation
city: Izhevsk
country: Russian Federation
city: Krasnodar
country: Russian Federation
city: Kursk
country: Russian Federation
city: Moscow
country: Russian Federation
city: Orenburg
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: Ufa
country: Russian Federation
city: Chernivtsi
country: Ukraine
city: Dnepropetrovsk
country: Ukraine
city: Kharkiv
country: Ukraine
city: Lutsk
country: Ukraine
city: Bebington
country: United Kingdom
city: Cardiff
country: United Kingdom
city: Edinburgh
country: United Kingdom
city: Glasgow
country: United Kingdom
city: Keighley
country: United Kingdom
city: Leeds
country: United Kingdom
city: Liverpool
country: United Kingdom
city: London
country: United Kingdom
city: Manchester
country: United Kingdom
city: Nottingham
country: United Kingdom
city: Oxford
country: United Kingdom
city: West Midlands
country: United Kingdom
Study officials:
affiliation: Incyte Corporation
name: Lance Leopold, M.D.
role: STUDY_DIRECTOR
References:
citation: Kristeleit R, Davidenko I, Shirinkin V, El-Khouly F, Bondarenko I, Goodheart MJ, Gorbunova V, Penning CA, Shi JG, Liu X, Newton RC, Zhao Y, Maleski J, Leopold L, Schilder RJ. A randomised, open-label, phase 2 study of the IDO1 inhibitor epacadostat (INCB024360) versus tamoxifen as therapy for biochemically recurrent (CA-125 relapse)-only epithelial ovarian cancer, primary peritoneal carcinoma, or fallopian tube cancer. Gynecol Oncol. 2017 Sep;146(3):484-490. doi: 10.1016/j.ygyno.2017.07.005. Epub 2017 Jul 8.