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

Sponsor

Incyte Corporation (Industry)

Overall Status

Terminated

CT.gov ID

NCT01685255

Collaborator

(none)

Enrollment

Locations

Arms

26.7

Duration (Months)

1.7

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Ovarian Cancer Genitourinary (GU) Tumors	Drug: Epacadostat Drug: tamoxifen	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

83 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Aug 1, 2012

Actual Primary Completion Date :

Oct 23, 2014

Actual Study Completion Date :

Oct 23, 2014

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Epacadostat Subjects randomized to Arm A (epacadostat) will take epacadostat tablets at a dose of 600 mg BID, beginning on Day 1.	Drug: Epacadostat Other Names: INCB024360
Active Comparator: Tamoxifen Subjects randomized to Arm B (tamoxifen) will take tamoxifen tablets at a dose of 20 mg BID, beginning on Day 1.	Drug: tamoxifen

Arm

Intervention/Treatment

Active Comparator: Epacadostat

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

Drug: Epacadostat

Other Names:

INCB024360

Active Comparator: Tamoxifen

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

Drug: tamoxifen

Outcome Measures

Primary Outcome Measures

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

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.]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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]).

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:

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.

Contacts and Locations

Locations

	City	State	Country
1	La Jolla	California	United States
2	Los Angeles	California	United States
3	San Francisco	California	United States
4	Evanston	Illinois	United States
5	Joliet	Illinois	United States
6	Iowa City	Iowa	United States
7	Covington	Louisiana	United States
8	Baltimore	Maryland	United States
9	Detroit	Michigan	United States
10	Minneapolis	Minnesota	United States
11	Bridgewater	New York	United States
12	Buffalo	New York	United States
13	Mineola	New York	United States
14	Durham	North Carolina	United States
15	Abington	Pennsylvania	United States
16	Philadelphia	Pennsylvania	United States
17	Greenville	South Carolina	United States
18	Bendigo		Australia
19	Heidelberg		Australia
20	Herston		Australia
21	Milton		Australia
22	Randwick		Australia
23	Calgary	Alberta	Canada
24	Toronto	Ontario	Canada
25	Montreal	Quebec	Canada
26	Ekaterinburg		Russian Federation
27	Izhevsk		Russian Federation
28	Krasnodar		Russian Federation
29	Kursk		Russian Federation
30	Moscow		Russian Federation
31	Orenburg		Russian Federation
32	St. Petersburg		Russian Federation
33	Ufa		Russian Federation
34	Chernivtsi		Ukraine
35	Dnepropetrovsk		Ukraine
36	Kharkiv		Ukraine
37	Lutsk		Ukraine
38	Bebington		United Kingdom
39	Cardiff		United Kingdom
40	Edinburgh		United Kingdom
41	Glasgow		United Kingdom
42	Keighley		United Kingdom
43	Leeds		United Kingdom
44	Liverpool		United Kingdom
45	London		United Kingdom
46	Manchester		United Kingdom
47	Nottingham		United Kingdom
48	Oxford		United Kingdom
49	West Midlands		United Kingdom