Study of AG-120 in Previously Treated Advanced Cholangiocarcinoma With IDH1 Mutations (ClarIDHy)
Condition: Advanced Cholangiocarcinoma; Metastatic Cholangiocarcinoma
MeSH terms: Cholangiocarcinoma
Intervention: AG-120; Placebo
Intervention description: Tablet administered orally; Tablet administered orally
Intervention MeSH terms: Ivosidenib
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Patients randomized in a 2:1 allocation (AG-120 vs Placebo)
Masking: Double (Participant, Investigator)
Enrollment: 187.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: IDH1

Summary:

      Study AG120-C-005 is a Phase 3, multicenter, randomized, double-blind, placebo-controlled
      study of orally administered AG-120. Participants, all personnel involved in the evaluation
      of participants' response to treatment (e.g., Investigators, study coordinators, study
      pharmacists), and designated Sponsor team members will be blinded to study treatment.
      Participants are required to have a histologically-confirmed diagnosis of isocitrate
      dehydrogenase-1 (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. Participants 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 participants must have received either a
      gemcitabine or a 5 fluorouracil (5-FU) based chemotherapy regimen.
    

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 Eastern Cooperative Oncology Group performance status (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 Response Evaluation
             Criteria in Solid Tumors (RECIST) v1.1. Participants 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). Participants
             must have received at least 1 gemcitabine- or 5-FU-containing regimen for advanced
             cholangiocarcinoma. Participants 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. Participants 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.