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.
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
Drug | Synonyms | Arms |
---|
AG-120 | | AG-120 experimental study drug |
AG-120 matched placebo | | AG-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
Name | Type | Description | Interventions |
---|
AG-120 experimental study drug | Active Comparator | AG-120, 500mg daily continuous dosing | |
AG-120 matched placebo | Placebo Comparator | 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 | |
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: | Active, not recruiting |
Lead Sponsor: | Agios Pharmaceuticals, Inc. |
Trial Keywords
Last Updated
May 21, 2021