Ivosidenib + Durvalumab + Chemotherapy for Cholangiocarcinoma

Recruiting in Palo Alto (17 mi)

+25 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Institut de Recherches Internationales Servier

Must not be taking: Immune therapy

Disqualifiers: Autoimmune disorders, Active infection, others

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?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.

Eligibility Criteria

This trial is for adults with advanced or metastatic cholangiocarcinoma (bile duct cancer) that has an IDH1 mutation. They must have a confirmed diagnosis, at least one measurable lesion, and meet specific blood count and liver function criteria. People with significant biliary obstruction not resolved before the study or other conditions affecting eligibility are excluded.

Inclusion Criteria

I have a tumor that can be measured by standard health scans.

My diagnosis is advanced or spread bile duct cancer that cannot be surgically removed.

My liver functions are within the required range.

+3 more

Exclusion Criteria

I may have significant nerve pain or damage that needs special approval.

My cancer returned more than 6 months after surgery and any follow-up treatment.

I've had one round of durvalumab plus gemcitabine/cisplatin for my advanced cancer, without needing dose changes for side effects.

+7 more

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Lead-In

Safety lead-in phase to determine the recommended combination dose (RDC) of ivosidenib in combination with durvalumab and gemcitabine/cisplatin

Approximately 8 weeks

Visits on days 1, 8, and 15 of Cycle 1, and days 1 and 8 of Cycle 2

Expansion

Expansion phase to assess the clinical activity of ivosidenib in combination with durvalumab and gemcitabine/cisplatin at the RDC

Approximately 5 years

Visits on day 1 of each 28-day cycle after Cycle 8

Follow-up

Participants are monitored for safety and effectiveness after treatment

Approximately 3 months

Safety follow-up visits approximately 30 days and 90 days after treatment ends, followed by survival follow-up every 3 months

Participant Groups

The trial tests Ivosidenib combined with Durvalumab and Gemcitabine/Cisplatin as first-line therapy for this type of cancer. It starts with a safety phase to find the best dose combination, followed by an expansion phase to assess clinical activity over cycles lasting 21-28 days each.

2Treatment groups

Experimental Treatment

Group I: Safety Lead-In PhaseExperimental Treatment5 Interventions

Group II: Expansion PhaseExperimental Treatment5 Interventions