Ivosidenib + Durvalumab + Chemotherapy for Cholangiocarcinoma

Recruiting at 43 trial locations

Overseen By Institut de Recherches Internationales Servier (I.R.I.S.) Clinical Studies Department

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Institut de Recherches Internationales Servier

Must not be taking: Immune therapy

Disqualifiers: Autoimmune disorders, Active infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 32

52 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combination for individuals with advanced cholangiocarcinoma, a type of bile duct cancer, who have a specific gene mutation called IDH1. Researchers are testing the safety and effectiveness of combining ivosidenib (a targeted therapy) with durvalumab (an immunotherapy) and the chemotherapy drugs gemcitabine and cisplatin. The trial begins by determining a safe dose and then assesses the treatment's effectiveness. Suitable candidates for this trial have cholangiocarcinoma that cannot be surgically removed and possess the IDH1 gene mutation. As a Phase 1, Phase 2 trial, it aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group.

Do I have to stop taking my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss your specific medications with the study team to get a clear answer.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the treatments in this trial have been studied for safety in various settings.

For ivosidenib, studies suggest a tolerable safety profile. While some side effects may occur, they are usually manageable. Patients have taken ivosidenib and found it beneficial without causing significant problems.

Durvalumab, when combined with chemotherapy, has improved patient outcomes. Most side effects were blood-related but similar to those seen with chemotherapy alone.

The combination of gemcitabine and cisplatin is a standard treatment for certain cancers. It has generally been safe, with manageable side effects.

In summary, research indicates that the treatments in this trial are generally well-tolerated. Evidence suggests they can be used safely, though side effects may occur. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Ivosidenib, Durvalumab, and chemotherapy for cholangiocarcinoma because it introduces a novel approach to treating this cancer. Ivosidenib is unique because it specifically targets and inhibits the mutated IDH1 enzyme, which is present in some cholangiocarcinoma tumors, potentially halting cancer growth. Durvalumab, an immune checkpoint inhibitor, helps the immune system recognize and attack cancer cells more effectively. Unlike the standard gemcitabine and cisplatin chemotherapy regimen, this combination aims to both directly target cancer cell mutations and enhance the body's immune response, offering a potentially more effective treatment for patients with specific genetic profiles.

What evidence suggests that this trial's treatments could be effective for cholangiocarcinoma?

Research has shown that the drug ivosidenib can extend the lives of people with IDH1-mutated cholangiocarcinoma, a specific type of liver cancer. One study found that patients lived for an average of 15.5 months. In this trial, participants will receive ivosidenib combined with other treatments. Another option in this trial is durvalumab, which, when paired with chemotherapy, has shown promise for advanced biliary tract cancers, with patients living an average of 12.8 months. Additionally, the combination of gemcitabine and cisplatin, also included in this trial, has proven effective, with survival times ranging from 4.6 to 11.7 months. Using these treatments together may offer a hopeful option for those with advanced cholangiocarcinoma. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

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.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Durvalumab
• Gemcitabine/Cisplatin
• Ivosidenib

Trial Overview 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.

How Is the Trial Designed?

Group I: Safety Lead-In Phase Experimental Treatment 5 Interventions

Group II: Expansion Phase Experimental Treatment 5 Interventions

Who Is Running the Clinical Trial?

Institut de Recherches Internationales Servier

Lead Sponsor

Trials

91

Recruited

67,100+

Citations

1. academic.oup.com academic.oup.com/oncolo/article/30/8/oyae306/7905746

Real-world effectiveness and prognostic factors of durvalumab ... Most patients are diagnosed at an advanced stage when treatment options are limited, contributing to an extremely poor prognosis with 5-year ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11377375/

Efficacy of durvalumab plus chemotherapy in advanced ... Durvalumab plus chemotherapy demonstrated significant improvements in PFS (6.77 vs. 4.99 months; hazard ratio 0.65 [95% CI 0.48–0.88]; P = 0.005) ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0168827825022019

3-year overall survival update from the phase III TOPAZ-1 ... At this DCO, the median (95% CI) follow-up time was 41.3 (39.3–44.1) months in all participants (durvalumab, 42.9 [39.8–44.3] months; placebo, 41.8 [36.7–46.2] ...

4. evidence.nejm.org evidence.nejm.org/doi/full/10.1056/EVIDoa2200015

Durvalumab plus Gemcitabine and Cisplatin in Advanced ... A phase 2 trial of durvalumab in combination with gemcitabine and cisplatin demonstrated promising efficacy, with an objective response rate of 72% and a ...

5. frontiersin.org frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1497415/full

Durvalumab and pembrolizumab in advanced biliary tract ... Patients treated with durvalumab (anti-PD-L1 therapy) plus gemcitabine and cisplatin achieved a median OS of 12.8 months and a median PFS of 7.2 ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40381735/

3-year overall survival update from the phase III TOPAZ-1 ... After a median 41.3 (95% CI 39.3-44.1) months' follow-up in all participants, median OS (95% CI) for durvalumab+GemCis vs. placebo+GemCis was 12.9 (11.6-14.1) ...

7. ejhp.bmj.com ejhp.bmj.com/content/32/Suppl_1/A193.2

5PSQ-093 Effectiveness and safety of durvalumab in ... Regarding toxicity, 92% had AEs of any grade with PtGem, 100% with PtGemDur and 99.4% in TOPAZ-1. The most frequent AEs were haematologic, 31% in historical ...