Ivosidenib for Bile Duct Cancer

(ProvIDHe Trial)

Recruiting at 21 trial locations

Overseen By Institut de Recherches Internationales Servier, Clinical Studies Department

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Servier

Must not be taking: IDH1 inhibitors, Steroids

Disqualifiers: Transplant, Brain metastases, Hepatitis, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: 28 days per cycle

220 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests ivosidenib for safety and effectiveness in people with bile duct cancer that cannot be removed or has spread. It focuses on patients with a specific gene mutation (IDH1) who have already tried other treatments. Participants will take ivosidenib tablets daily and visit the study site regularly. It suits those diagnosed with non-operable bile duct cancer who have undergone one type of systemic treatment and recovered from side effects. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have received systemic cancer treatment or radiotherapy within 2 weeks before starting the trial, and certain other treatments within 4 weeks.

Is there any evidence suggesting that ivosidenib is likely to be safe for humans?

Studies have shown that ivosidenib is generally well-tolerated by patients with advanced bile duct cancer. More than 15% of patients experience common side effects like tiredness, nausea, stomach pain, diarrhea, and cough, which are usually manageable and not severe. The FDA has already approved ivosidenib for other conditions, such as acute myeloid leukemia, indicating it has undergone thorough safety testing. Although serious side effects can occur, they are less common. Overall, previous research supports the safety of ivosidenib for treating bile duct cancer. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for bile duct cancer?

Ivosidenib is unique because it specifically targets a genetic mutation known as IDH1, which is found in some bile duct cancers. Unlike traditional chemotherapy treatments that attack rapidly dividing cells in general, Ivosidenib zeroes in on this mutation, potentially offering a more targeted and less harmful approach. Researchers are excited about Ivosidenib because it offers a new way to tackle cancer by interfering with the tumor's metabolism, potentially leading to better outcomes for patients who have few effective treatment options.

What evidence suggests that ivosidenib might be an effective treatment for bile duct cancer?

Research has shown that ivosidenib, the treatment under study in this trial, effectively treats cholangiocarcinoma, particularly in patients with the IDH1 gene mutation. One study found that patients taking ivosidenib lived without cancer progression for an average of 4.7 months and had an overall survival of 15.5 months on average. Another study reported an average of 5.1 months before cancer progression. Ivosidenib also significantly reduced the risk of cancer worsening or causing death. The FDA has approved ivosidenib for advanced or metastatic cholangiocarcinoma, underscoring its effectiveness. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for adults with advanced or metastatic cholangiocarcinoma (bile duct cancer) that can't be removed by surgery. Participants must have tried at least one systemic therapy, carry a specific IDH1 gene mutation, and have recovered from previous treatment side effects. Women of childbearing age and men with partners of childbearing potential must agree to use two forms of contraception.

Inclusion Criteria

I agree to use two forms of birth control during and for 1 month after the study.

I have had one treatment for bile duct cancer and recovered from side effects.

My disease has a specific IDH1 gene mutation.

Exclusion Criteria

I haven't had cancer treatment or radiotherapy in the last 2 weeks.

I have been treated with an IDH1 inhibitor before.

I have had an organ or tissue transplant.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive ivosidenib tablets orally once daily for 28-day cycles, continuing as long as clinical benefit and consent are maintained

28 days per cycle

1 visit per cycle (in-person)

Withdrawal

A withdrawal visit occurs within 42 days of stopping treatment

6 weeks

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up visits every 6 months for up to 18 months

18 months

3 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Ivosidenib

Trial Overview

The study tests the safety and effectiveness of Ivosidenib oral tablets in treating bile duct cancer. Patients take the medication daily in 28-day cycles, continuing if beneficial. The study includes a minimum of six visits over an initial cycle plus follow-up visits on day one of each additional cycle up to 18 months.

How Is the Trial Designed?

Group I: Ivosidenib Experimental Treatment 1 Intervention

Ivosidenib 500 mg, taken orally as two 250 mg tablets once daily for an unlimited amount of continuous 28-day cycles

Ivosidenib is already approved in United States, European Union for the following indications:

Approved in United States as Tibsovo for:

• Acute myeloid leukemia (AML) with IDH1 mutation

Approved in European Union as Tibsovo for:

• Acute myeloid leukemia (AML) with IDH1 mutation

Who Is Running the Clinical Trial?

Servier

Lead Sponsor

Trials

55

Recruited

45,600+

Servier Affaires Médicales

Lead Sponsor

Trials

14

Recruited

15,100+

Published Research Related to This Trial

Ivosidenib, a reversible inhibitor of mutant IDH1, has shown improved progression-free survival in patients with advanced cholangiocarcinoma, with a median of 2.7 months compared to 1.4 months for placebo, indicating its efficacy as a treatment option.

The drug is well tolerated with good oral exposure and a long half-life, suggesting it could be a safe and effective choice for patients who have not responded to prior chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ivosidenib: an investigational drug for the treatment of biliary tract cancers. Angelakas, A., Lamarca, A., Hubner, RA., et al.[2021]

Ivosidenib, an IDH1 inhibitor, significantly improves progression-free survival (2.7 months) and overall survival (10.3 months) in patients with chemorefractory IDH1-mutated cholangiocarcinoma compared to placebo, indicating its efficacy as a targeted therapy.

The treatment with ivosidenib is associated with a very low incidence of severe adverse events and less decline in health-related quality of life, enhancing patient adherence and clinician confidence in its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ivosidenib in IDH1-mutated cholangiocarcinoma: Clinical evaluation and future directions. Lavacchi, D., Caliman, E., Rossi, G., et al.[2022]

Ivosidenib significantly improves overall survival in patients with advanced cholangiocarcinoma who have IDH1 mutations, with a median survival of 10.3 months compared to 7.5 months for those receiving a placebo.

The survival benefit is even more pronounced, with a difference of 5.1 months when considering patients who crossed over to the treatment group after initially receiving placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ivosidenib Boosts OS in Cholangiocarcinoma. [2022]

Ivosidenib, an IDH1 inhibitor, significantly improved progression-free survival in patients with IDH1 mutated cholangiocarcinoma, with a median of 2.7 months compared to 1.4 months for placebo (p < 0.0001).

While overall survival showed a trend towards improvement with 10.8 months for ivosidenib versus 9.7 months for placebo (p = 0.06), the results suggest that ivosidenib is a promising treatment option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Utility of Ivosidenib in the Treatment of IDH1-Mutant Cholangiocarcinoma: Evidence To Date. Uson Junior, PLS., Borad, MJ.[2023]

In a real-world study of 8 patients with IDH1-mutated cholangiocarcinoma treated with ivosidenib, the median progression-free survival was 4.4 months, aligning with results from the phase III ClarIDHy trial.

The treatment was generally well-tolerated, with only 12.5% of patients experiencing treatment-related adverse events, and no severe (grade 3 or higher) adverse events reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Data on Ivosidenib in Patients with Previously Treated Isocitrate Dehydrogenase 1-Mutated Intrahepatic Cholangiocarcinomas: An Early Exploratory Analysis. Rimini, M., Burgio, V., Antonuzzo, L., et al.[2022]

Ivosidenib is an effective treatment for adults with pretreated, advanced cholangiocarcinoma harboring mutant IDH1, significantly prolonging progression-free survival and improving disease control rates compared to placebo in the phase 3 ClarIDHy study.

The treatment is generally well tolerated, with common side effects being low-grade diarrhea, nausea, and fatigue, while also preserving health-related quality of life in areas such as physical function and appetite.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ivosidenib: A Review in Advanced Cholangiocarcinoma. Frampton, JE.[2023]

Comprehensive genomic profiling has revealed that biliary tract cancers, previously considered difficult to treat, contain many actionable genetic mutations, particularly in IDH1/2 and fibroblast growth factor receptor genes.

The IDH1 inhibitor ivosidenib has shown a survival benefit in cholangiocarcinoma patients with IDH1 mutations in a phase III trial, marking a significant advancement in targeted therapy for these cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IDH Signalling Pathway in Cholangiocarcinoma: From Biological Rationale to Therapeutic Targeting. Salati, M., Caputo, F., Baldessari, C., et al.[2020]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8461552/

Final Overall Survival Efficacy Results of Ivosidenib for ...

The median survival among patients with advanced disease is approximately less than 12 months, with 5-year survival rates of 10% or less. Most ...

2.

tibsovo.com

tibsovo.com/cca/results

tibsovo results: cholangiocarcinoma (cca) clinical trial

The TIBSOVO clinical trial was designed to determine if once-daily TIBSOVO could reduce the risk of disease progression or death in patients with advanced ...

3.

onclive.com

onclive.com/view/ivosidenib-has-preliminary-real-world-activity-in-idh1-mutated-cholangiocarcinoma

Ivosidenib Has Preliminary Real-World Activity in IDH1 ...

Ivosidenib showed promising efficacy in IDH1-mutated cholangiocarcinoma, with a median PFS of 4.7 months and OS of 15.5 months in the ProvIDHe ...

4.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e16227

Real-world survival outcomes with ivosidenib in Chinese ...

The median progression-free survival (PFS) from initiation of treatment with ivosidenib was 5.1 months (range: 2.0-28.5), and the median overall ...

5.

fda.gov

fda.gov/drugs/resources-information-approved-drugs/fda-approves-ivosidenib-advanced-or-metastatic-cholangiocarcinoma

FDA approves ivosidenib for advanced or metastatic ...

The trial demonstrated a statistically significant improvement in PFS for patients randomized to ivosidenib (HR 0.37; 95% CI: 0.25, 0.54; p<0. ...

6.

tibsovo.com

tibsovo.com/

TIBSOVO® (ivosidenib tablets)

#1 Prescribed FDA-Approved · Acute myeloid leukemia (AML) · MYELODYSPLASTIC SYNDROMES (MDS) · Cholangiocarcinoma (bile duct cancer) · IMPORTANT SAFETY INFORMATION.

7.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/31300360/

Safety and activity of ivosidenib in patients with IDH1-mutant ...

Ivosidenib is under clinical evaluation in a phase 1 study that aims to assess its safety and tolerability in patients with mIDH1 solid tumours.

8.

tibsovopro.com

tibsovopro.com/cca/faqs

FAQs | CCA - TIBSOVO® (ivosidenib tablets)

The most common adverse reactions (≥15%) in patients with advanced mIDH1 cholangiocarcinoma were fatigue, nausea, abdominal pain, diarrhea, cough, decreased ...

9.

tibsovo.com

tibsovo.com/cca

Bile Duct Cancer Treatment | TIBSOVO® (ivosidenib tablets)

It is not known if TIBSOVO is safe and effective in children. IMPORTANT SAFETY INFORMATION. TIBSOVO may cause serious side effects, including: Changes in the ...

10.

jamanetwork.com

jamanetwork.com/journals/jamaoncology/fullarticle/2784216

Final Overall Survival Efficacy Results of Ivosidenib for ...

Ivosidenib treatment resulted in numerically improved overall survival benefits vs placebo, despite a high rate of crossover.