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

Overview

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.

Full Title of Study: “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”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Double (Participant, Investigator)
  • Study Primary Completion Date: January 2019

Interventions

  • Drug: AG-120
  • Drug: AG-120 matched placebo

Arms, Groups and Cohorts

  • Active Comparator: AG-120 experimental study drug
    • AG-120, 500mg daily continuous dosing
  • 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

Clinical Trial Outcome Measures

Primary Measures

  • Progression Free Survival (PFS)
    • Time Frame: Up to 26 weeks, on average

Secondary Measures

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

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Agios Pharmaceuticals, Inc.
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Medical Affairs Agios Pharmaceuticals, Inc., Study Chair, Agios Pharmaceuticals, Inc.

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