A Phase 3 study to test for efficacy of an oral investigational drug, AG-120, in patients with nonresectable or metastatic cholangiocarcinoma with an IDH1 mutatio
- Conditions
- onresectable or Metastatic CholangiocarcinomaMedDRA version: 20.0Level: LLTClassification code 10008594Term: Cholangiocarcinoma non-resectableSystem Organ Class: 100000054936MedDRA version: 20.0Level: LLTClassification code 10077846Term: Cholangiocarcinoma metastaticSystem Organ Class: 100000054936Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2015-005117-72-FR
- Lead Sponsor
- Agios Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 186
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.
8. Have recovered from toxicities associated with prior anticancer therapy to baseline unless stabilized under medical management.
9. Have adequate bone marrow function as evidenced by:
a. Absolute neutrophil count =1,500/mm^3 or 1.5 ×109/L
b. Hemoglobin =8 g/dL
c. Platelets =100,000/mm^3 or 100 × 109/L
10. Have adequate hepatic function as evidenced by:
a. Serum total bilirubin =2 × upper limit of normal (ULN), unless considered due to Gilbert’s disease
b. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =5 × ULN
11. Have adequate renal 11. function as evidenced by:
a. Serum creatinine <1.5 × ULN
OR
b. Creatinine clearance =50 mL/min based on the Cockroft-Gault glomerular filtration rate (GFR) estimation: (140 - Age) × (weight in kg) × (0.85 if female)/72 × serum creatinine
12. Be able to understand and willing and able to sign the informed consent and comply with scheduled visits, treatment plans, procedures and laboratory tests including serial peripheral blood sampling and urine sampling, during the study.
13. Female subjects with reproductive potential must have a negative serum pregnancy test prior to the start of therapy, or a confirmation from an obstetrician in case of equivocal serum pregnancy results. Females of reproductive potential are defined as sexually mature women who have not undergone a hysterectomy, bilateral oophorectomy, or tubal occlusion or who have not been naturally postmenopausal (i.e., who have not menstruated) for at least 24 consecutive months (i.e., have not had menses at any time in the preceding 24 consecutive months). Women of reproductive potential, as well as fertile men and their partners who are female with reproductive potential, must agree to abstain from sexual intercourse or to use a highly effective form of contraception from the time of giving informed consent, during the study, and for 90 days (females and males) following the last dose of study drug. A highly effective form of contraception is defined as hormonal oral contraceptives, injectables, patches, intrauterine devic
1. Received a prior IDH inhibitor.
2. Received systemic anticancer therapy or 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, havediscontinued 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.
6. Have a history of another primary cancer, with the exception 6. of: a) curatively resected non-melanoma skin cancer; b) curatively treated cervical carcinoma in situ; or c) other primary solid or liquid tumor with no known active disease present that, in the opinion of the Investigator, will not affect subject outcome in the setting of current cholangiocarcinoma diagnosis.
7. Underwent major surgery within 4 weeks of Day 1 or have not recovered from postsurgery toxicities.
8. Are pregnant or breastfeeding.
9. Are taking known strong CYP3A4 inducers or inhibitors, or sensitive CYP3A4 substrate medications, unless they can be transferred to other medications within =5 half-lives prior to dosing, or unless the medications can be properly monitored during the study.
10. Are taking P-gp transporter-sensitive substrate medications or inhibitors unless they can be transferred to other medications within =5 half-lives prior to administration of study treatment, or unless the medications can be properly monitored during the study.
11. Have an active infection requiring systemic anti-infective therapy or with an unexplained fever >38.5°C within 7 days of Day 1 (at the discretion of the Investigator, subjects with tumor fever may be enrolled).
12. Have any known hypersensitivity to any of the components of AG-120 or the matched placebo.
13. Have significant active cardiac disease within 6 months prior to the start of study treatment, including New York Heart Association (NYHA) Class III or IV congestive heart failure; myocardial infarction; unstable angina; and/or stroke.
14. Have LVEF <40% by ECHO and/or MUGA scan obtained within 28 days prior to the start of study treatment.
15. Have a heart-rate corrected QT interval (using Fredericia’s formula) (QTcF) =450 msec or other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome). Bundle branch block and prolonged QTcF interval are permitted with approval of the Medical Monitor.
16. Are taking medications that are known to prolong the QT interval, unless they can be transferred to other medications within =5 half-lives prior to dosing or unless the medications can be properly monitored during the study. (If equivalent medication is not available, QTcF should be closely monitored.)
17. Have known active hepatitis B (HBV) or hepatitis C (HCV) infections, known positive human immunodeficiency virus
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method