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

NCT01685255 | Terminated Phase 2 DMC

• 1 other identifier: INCB 24360-210
• Study Type: interventional
• Target: 83
• Locations: 6 countries
• Sites: 49

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.

Conditions

Ovarian Cancer; Genitourinary (GU) Tumors

Keywords

FIGO Stage III or IV EOC; PPC FTC; increasing CA 125

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• 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.

Study Arms (2)

Epacadostat

ACTIVE COMPARATOR

Subjects randomized to Arm A (epacadostat) will take epacadostat tablets at a dose of 600 mg BID, beginning on Day 1.

Drug: Epacadostat

Tamoxifen

ACTIVE COMPARATOR

Subjects randomized to Arm B (tamoxifen) will take tamoxifen tablets at a dose of 20 mg BID, beginning on Day 1.

Drug: tamoxifen

Interventions

Epacadostat DRUG

Also known as: INCB024360

Epacadostat

tamoxifen DRUG

Tamoxifen

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Incyte Corporation: lead

Study Sites (49)

Unknown Facility

La Jolla, California, United States

Location

Unknown Facility

Los Angeles, California, United States

Location

Unknown Facility

San Francisco, California, United States

Location

Unknown Facility

Evanston, Illinois, United States

Location

Unknown Facility

Joliet, Illinois, United States

Location

Unknown Facility

Iowa City, Iowa, United States

Location

Unknown Facility

Covington, Louisiana, United States

Location

Unknown Facility

Baltimore, Maryland, United States

Location

Unknown Facility

Detroit, Michigan, United States

Location

Unknown Facility

Minneapolis, Minnesota, United States

Location

Unknown Facility

Bridgewater, New York, United States

Location

Unknown Facility

Buffalo, New York, United States

Location

Unknown Facility

Mineola, New York, United States

Location

Unknown Facility

Durham, North Carolina, United States

Location

Unknown Facility

Abington, Pennsylvania, United States

Location

Unknown Facility

Philadelphia, Pennsylvania, United States

Location

Unknown Facility

Greenville, South Carolina, United States

Location

Unknown Facility

Bendigo, Australia

Location

Unknown Facility

Heidelberg, Australia

Location

Unknown Facility

Herston, Australia

Location

Unknown Facility

Milton, Australia

Location

Unknown Facility

Randwick, Australia

Location

Unknown Facility

Calgary, Alberta, Canada

Location

Unknown Facility

Toronto, Ontario, Canada

Location

Unknown Facility

Montreal, Quebec, Canada

Location

Unknown Facility

Izhevsk, Russia

Location

Unknown Facility

Krasnodar, Russia

Location

Unknown Facility

Kursk, Russia

Location

Unknown Facility

Moscow, Russia

Location

Unknown Facility

Orenburg, Russia

Location

Unknown Facility

Saint Petersburg, Russia

Location

Unknown Facility

Ufa, Russia

Location

Unknown Facility

Yekaterinburg, Russia

Location

Unknown Facility

Chernivtsi, Ukraine

Location

Unknown Facility

Dnipro, Ukraine

Location

Unknown Facility

Kharkiv, Ukraine

Location

Unknown Facility

Lutsk, Ukraine

Location

Unknown Facility

Bebington, United Kingdom

Location

Unknown Facility

Cardiff, United Kingdom

Location

Unknown Facility

Edinburgh, United Kingdom

Location

Unknown Facility

Glasgow, United Kingdom

Location

Unknown Facility

Keighley, United Kingdom

Location

Unknown Facility

Leeds, United Kingdom

Location

Unknown Facility

Liverpool, United Kingdom

Location

Unknown Facility

London, United Kingdom

Location

Unknown Facility

Manchester, United Kingdom

Location

Unknown Facility

Nottingham, United Kingdom

Location

Unknown Facility

Oxford, United Kingdom

Location

Unknown Facility

West Midlands, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 28698009 DERIVED

MeSH Terms

Conditions

Ovarian Neoplasms; Neoplasms

Interventions

epacadostat; Tamoxifen

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Lance Leopold, M.D.

  Incyte Corporation

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 4, 2012
• First Posted: September 14, 2012
• Study Start: August 1, 2012
• Primary Completion: October 23, 2014
• Study Completion: October 23, 2014
• Last Updated: March 11, 2019

Record last verified: 2019-03

Locations

AU (5); CA (3); US (17); RU (8); UA (4); GB (12)