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Ivosidenib Plus Durvalumab and Gemcitabine/Cisplatin as First-Line Therapy in Participants With Locally Advanced or Metastatic Cholangiocarcinoma With an IDH1 Mutation

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Conditions

Locally Advanced, Unresectable or Metastatic Cholangiocarcinoma With an IDH1 Mutation

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

The objective of this study is to investigate the safety, tolerability and preliminary activity of ivosidenib in combination with durvalumab and gemcitabine/cisplatin as first-line therapy in participants with locally advanced, unresectable or metastatic cholangiocarcinoma with an IDH1 mutation. The study will begin with a safety lead-in phase (Phase 1b study) to determine the recommended combination dose (RDC) and then will transition to an expansion phase (Phase 2 study) to assess the clinical activity of ivosidenib in combination with durvalumab and gemcitabine/cisplatin at the RCD. During the treatment period participants will have study visits on days 1, 8, and 15 of Cycle 1, on days 1 and 8 of Cycle 2 to 8, and on day 1 of each additional cycle. Cycles 1 through 8 are 21 day cycles, and each following cycle is 28 days. Approximately 30 days and 90 days after treatment has ended, safety follow-up visits will occur and then participants will be followed for survival every 3 months. Study visits may include blood tests, ECG, vital signs, and a physical examination.

Official Title

A Phase 1b/2, Safety Lead-in and Dose-Expansion, Open Label, Multicenter Trial Investigating the Safety, Tolerability, and Preliminary Activity of Ivosidenib in Combination With Durvalumab and Gemcitabine/Cisplatin as First-line Therapy in Participants With Locally Advanced, Unresectable or Metastatic Cholangiocarcinoma With an IDH1 Mutation

Quick Facts

Study Start:2024-12-16
Study Completion:2027-09-13
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:RECRUITING

Study ID

NCT06501625

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years
Sexes Eligible for Study:ALL
Accepts Healthy Volunteers:No
Standard Ages:ADULT, OLDER_ADULT
Inclusion CriteriaExclusion Criteria
  1. * Have a histopathological confirmed diagnosis consistent with locally advanced unresectable or metastatic cholangiocarcinoma.
  2. * Have documented IDH1 gene-mutated cholangiocarcinoma based on local or central laboratory testing (R132C/L/G/H/S mutation variants tested).
  3. * Have at least one evaluable and measurable lesion as defined by RECIST v1.1.
  4. * Have adequate bone marrow function as evidenced by:
  5. * Absolute neutrophil count ≥ 1,500/mm3 or 1.5 ×109/L
  6. * Hemoglobin ≥ 9 g/dL
  7. * Platelet count ≥ 100,000/mm3 or 100 × 109/L
  8. * Have adequate hepatic function as evidenced by:
  9. * Serum bilirubin ≤ 2.0 × the upper limit of normal (ULN); this will not apply to patients with confirmed Gilbert's syndrome. Any clinically significant biliary obstruction should be resolved before randomization
  10. * Aspartate aminotransferase (AST), and alanine aminotransferase (ALT) ≤ 2.5 × ULN; for patients with hepatic metastases, ALT and AST ≤ 5.0 × ULN
  11. * Have adequate renal function, defined as: creatinine clearance \> 60 mL/min per 24 hour urine or as calculated on the Cockcroft-Gault formula (using actual body weight):
  1. * Received treatment for locally advanced, unresectable or metastatic disease with the following exceptions:
  2. * Treatment with up to one cycle of durvalumab plus gemcitabine/cisplatin treatment is permitted before study participation. Note: For the Safety Lead-In Phase, participants who received one prior cycle of durvalumab plus gemcitabine/cisplatin and required dose modifications for treatment-related toxicity are excluded.
  3. * Patients who developed recurrent disease \> 6 months after surgery with curative intent, and, if given, \> 6 months after the completion of adjuvant (chemotherapy and/or radiation).
  4. * Prior exposure to immune-mediated therapy, including, but not limited to, anti-PD-1or other anti-PD-L1, and anti-PD-L2, anti-CTLA-4 antibodies, excluding therapeutic anticancer vaccines.
  5. * Unresolved Grade ≥2 adverse events from a previous anticancer therapy, with the exception of alopecia and vitiligo and the laboratory values listed in the inclusion criteria.
  6. * Patients with Grade ≥2 neuropathy to be evaluated on a case-by-case basis after consultation with the medical monitor
  7. * Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with ivosidenib may be included only after consultation with the medical monitor
  8. * Participation in another interventional study at the same time or within 14 days prior to the first study medication (triple combination treatment) administration. For patients having participated to another prior interventional study, the first dose of ivosidenib should occur after a period greater than or equal to 5 half-lives or 28 days, whichever is shorter of the last dose of the prior investigational product.
  9. * Active or prior documented autoimmune or inflammatory disorders including:
  10. * inflammatory bowel disease (e.g., colitis or Crohn's disease)
  11. * diverticulitis (with the exception of diverticulosis)
  12. * systemic lupus erythematosus
  13. * Sarcoidosis syndrome
  14. * Wegener syndrome (granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.)
  15. * chronic skin condition that does not require systemic therapy
  16. * vitiligo
  17. * alopecia
  18. * hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement therapy
  19. * unmedicated celiac disease that is controlled by diet
  20. * Have heart rate-corrected QT interval using Fridericia's formula (QTcF) of ≥ 450 msec or with other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome/sudden death, polymorphic ventricular arrhythmia). The Sponsor should review participants with bundle branch block and prolonged QTcF for potential inclusion.
  21. * Have an active infection, including:
  22. * Hepatitis B (clinical evaluation includes: presence of hepatitis B surface antigen \[HBsAg\] and/or anti-HBcAb with detectable hepatitis B virus \[HBV\] DNA ≥ 10 IU/mL)
  23. * Hepatitis C
  24. * Tuberculosis (clinical evaluation includes: clinical history, physical examination and/or radiographic findings, and tuberculosis testing as per local practice)
  25. * Human immunodeficiency virus (clinical evaluation includes: positive HIV 1/2 antibodies) Note: Patients with a resolved or past HBV infection (i.e., presence of hepatitis B core antibody \[anti-HBc\] and absence of HBsAg) do not need to be excluded from the study. Patients positive for hepatitis C (HCV) antibody are eligible only if the polymerase chain reaction is negative for HCV RNA.

Contacts and Locations

Study Contact

Institut de Recherches Internationales Servier (I.R.I.S.) Clinical Studies Department
CONTACT
+33 1 55 72 60 00
scientificinformation@servier.com

Study Locations (Sites)

Usc Norris Comprehensive Cancer Center
Los Angeles, California, 90033
United States
Moffitt Cancer Center
Tampa, Florida, 33612
United States
Northwestern Medicine
Chicago, Illinois, 60611
United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
United States
Gibbs Cancer Center
Spartanburg, South Carolina, 29303
United States
Fred Hutchinson Cancer Center
Seattle, Washington, 98109
United States

Collaborators and Investigators

Sponsor: Institut de Recherches Internationales Servier

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-12-16
Study Completion Date2027-09-13

Study Record Updates

Study Start Date2024-12-16
Study Completion Date2027-09-13

Terms related to this study

Additional Relevant MeSH Terms

  • Locally Advanced, Unresectable or Metastatic Cholangiocarcinoma With an IDH1 Mutation