Clinical Trials /

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

NCT02989857

Description:

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.

Related Conditions:
  • Cholangiocarcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: AG120-C-005
  • NCT ID: NCT02989857

Conditions

  • Advanced Cholangiocarcinoma
  • Metastatic Cholangiocarcinoma

Interventions

DrugSynonymsArms
AG-120AG-120 experimental study drug
AG-120 matched placeboAG-120 matched placebo

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
AG-120 experimental study drugActive ComparatorAG-120, 500mg daily continuous dosing
  • AG-120
AG-120 matched placeboPlacebo ComparatorAG-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
  • AG-120 matched placebo

Eligibility Criteria

        Inclusion Criteria:

          1. Be ≥18 years of age.

          2. 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.

          3. 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).

          4. Have an ECOG PS score of 0 or 1

          5. Have an expected survival of ≥3 months.

          6. 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.

          7. 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:

          1. Received a prior IDH inhibitor.

          2. 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.

          3. Received radiotherapy to metastatic sites of disease <2 weeks prior to Day 1.

          4. Underwent hepatic radiation, chemoembolization, and radiofrequency ablation <4 weeks
             prior to Day 1.

          5. 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression Free Survival (PFS)
Time Frame:Up to 26 weeks, on average
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Adverse Event (AE) and Serious Adverse Event (SAE) analysis
Time Frame:Up to 26 weeks, on average
Safety Issue:
Description:
Measure:Overall Survival (OS)
Time Frame:Up to 52 weeks, on average
Safety Issue:
Description:
Measure:Overall Response Rate (ORR)
Time Frame:Up to 26 weeks, on average
Safety Issue:
Description:
Measure:Quality of Life (QOL)
Time Frame:Up to 52 weeks, on average
Safety Issue:
Description:Method of assessment will be questionnaires. Questionnaire: EORTC QLQ-C30
Measure:Quality of Life (QOL)
Time Frame:Up to 52 weeks, on average
Safety Issue:
Description:Method of assessment will be questionnaires. Questionnaire: EORTC QLQ-Bil21
Measure:Quality of Life (QOL)
Time Frame:Up to 52 weeks, on average
Safety Issue:
Description:Method of assessment will be questionnaires. Questionnaire: PGI-C/PGI-S
Measure:Health Economic Outcomes
Time Frame:Up to 26 weeks, on average
Safety Issue:
Description:Method of assessment will be questionnaires. Questionnaire: EuroQOL EQ-5D-5L

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Agios Pharmaceuticals, Inc.

Trial Keywords

  • IDH1

Last Updated

February 22, 2018