Study of AG-120 in Previously Treated Advanced Cholangiocarcinoma With

Study of AG-120 in Previously Treated Advanced Cholangiocarcinoma With IDH1 Mutations (ClarIDHy) (ClarIDHy)

Study AG120-C-005 is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study of orally administered AG-120. Subjects, all personnel involved in the evaluation of subjects’ response to treatment (e.g., Investigators, study coordinators, study pharmacists), and designated Sponsor team members will be blinded to study treatment. Subjects are required to have a histologically-confirmed diagnosis of IDH1 gene-mutated cholangiocarcinoma that is not eligible for curative resection, transplantation, or ablative therapies prior to enrollment.IDH1 mutation testing will be performed at participating investigative sites. Subjects must have progression of disease and have received at least 1 but not more than 2 prior treatment regimens for advanced disease (nonresectable or metastatic). All subjects must have received either a gemcitabine or a 5 fluorouracil (5-FU) based chemotherapy regimen.

Condition Intervention Phase
Advanced Cholangiocarcinoma
Metastatic Cholangiocarcinoma
Drug: AG-120
Drug: AG-120 matched placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-controlled Study of AG-120 in Previously-treated Subjects With Nonresectable or Metastatic Cholangiocarcinoma With an IDH1 Mutation

Resource links provided by NLM:

Genetics Home Reference related topics: cholangiocarcinoma
U.S. FDA Resources

Further study details as provided by Agios Pharmaceuticals, Inc.:

Primary Outcome Measures:
Progression Free Survival (PFS) [ Time Frame: Up to 26 weeks, on average ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
Adverse Event (AE) and Serious Adverse Event (SAE) analysis [ Time Frame: Up to 26 weeks, on average ] [ Designated as safety issue: Yes ]
Overall Survival (OS) [ Time Frame: Up to 52 weeks, on average ] [ Designated as safety issue: No ]
Overall Response Rate (ORR) [ Time Frame: Up to 26 weeks, on average ] [ Designated as safety issue: No ]
Quality of Life (QOL) [ Time Frame: Up to 52 weeks, on average ] [ Designated as safety issue: No ]
Method of assessment will be questionnaires. Questionnaire: EORTC QLQ-C30

Quality of Life (QOL) [ Time Frame: Up to 52 weeks, on average ] [ Designated as safety issue: No ]
Method of assessment will be questionnaires. Questionnaire: EORTC QLQ-Bil21

Quality of Life (QOL) [ Time Frame: Up to 26 weeks, on average ] [ Designated as safety issue: No ]
Method of assessment will be questionnaires. Questionnaire: EuroQOL EQ-5D-5L

Estimated Enrollment: 186
Study Start Date: December 2016
Estimated Study Completion Date: August 2020
Estimated Primary Completion Date: November 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: AG-120 experimental study drug
AG-120, 500mg daily continuous dosing
Drug: AG-120
Placebo Comparator: AG-120 matched placebo
AG-120 matched placebo, daily continuous dosing. Subjects who experience disease progression and were receiving placebo, will be allowed to cross-over and receive AG-120
Drug: AG-120 matched placebo

Eligibility

Ages Eligible for Study: 18 Years and older (Adult, Senior)
Genders Eligible for Study: Both
Accepts Healthy Volunteers: No
Criteria
Inclusion Criteria:

Be ≥18 years of age.
Have a histopathological diagnosis (fresh or banked tumor biopsy sample, preferably collected within the last 3 years) of nonresectable or metastatic cholangiocarcinoma and are not eligible for curative resection, transplantation, or ablative therapies.
Have documented IDH1 gene-mutated disease (from a fresh tumor biopsy or the most recent banked tumor tissue available) based on central laboratory testing (R132C/L/G/H/S mutation variants tested).
Have an ECOG PS score of 0 or 1
Have an expected survival of ≥3 months.
Have at least one evaluable and measurable lesion as defined by RECIST v1.1. Subjects who have received prior local therapy (including but not limited to embolization, chemoembolization, radiofrequency ablation, or radiation therapy) are eligible provided measurable disease falls outside of the treatment field or within the field and has shown ≥20% growth in size since post-treatment assessment.
Have documented disease progression following at least 1 and no more than 2 prior systemic regimens for advanced disease (nonresectable or metastatic). Subjects must have received at least 1 gemcitabine- or 5-FU-containing regimen for advanced cholangiocarcinoma. Subjects who have received systemic adjuvant chemotherapy will be permitted provided there is documented disease progression during or within 6 months of completing the therapy.
Exclusion criteria:

Received a prior IDH inhibitor.
Received systemic anticancer therapy or an investigational agent <2 weeks prior to Day 1 (washout from prior immune based anticancer therapy is 4 weeks). In addition, the first dose of study treatment should not occur before a period ≥5 half-lives of the investigational agent has elapsed.
Received radiotherapy to metastatic sites of disease <2 weeks prior to Day 1.
Underwent hepatic radiation, chemoembolization, and radiofrequency ablation <4 weeks prior to Day 1.
Have known symptomatic brain metastases requiring steroids. Subjects with previously diagnosed brain metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to study entry, have discontinued corticosteroid treatment for these metastases for at least 4 weeks and have radiographically stable disease for at least 3 months prior to study entry. Note: up to 10 mg per day of prednisone equivalent will be allowed.
Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02989857

Contacts
Contact: Medical Affairs Agios Pharmaceuticals, Inc. 844-633-2332 MedAffairs.Requests@agios.com

Locations
United States, Tennessee
Sarah Cannon Research Institute Not yet recruiting
Nashville, Tennessee, United States
Sponsors and Collaborators
Agios Pharmaceuticals, Inc.
Investigators
Study Chair: Medical Affairs Agios Pharmaceuticals, Inc. Agios Pharmaceuticals, Inc.
More Information

Responsible Party: Agios Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT02989857 History of Changes
Other Study ID Numbers: AG120-C-005
Study First Received: December 5, 2016
Last Updated: December 9, 2016
Health Authority: United States: Food and Drug Administration
Individual Participant Data
Plan to Share IPD: No

Keywords provided by Agios Pharmaceuticals, Inc.:
IDH1

Additional relevant MeSH terms:
Cholangiocarcinoma
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms

ClinicalTrials.gov processed this record on December 13, 2016

https://clinicaltrials.gov/ct2/show/NCT02989857