Ivosidenib for Bile Duct Cancer

(ProvIDHe Trial)

Recruiting at 22 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

Trial Summary

What is the purpose of this trial?

A Phase 3b research study to consolidate the data that ivosidenib is safe and effective in adult patients with previously treated, locally advanced, or metastatic cholangiocarcinoma (CCA). All patients who meet inclusion criteria will be enrolled to receive ivosidenib tablets orally once daily for 28 day cycles, continuing as long as clinical benefit and consent for participation is maintained. There will be a minimum of 6 study visits from screening until the final follow-up, if one cycle of treatment is completed and consent is maintained through 18 months of follow-up. Each additional cycle completed will add one study visit, on the first day of each cycle.

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.

What data supports the effectiveness of the drug Ivosidenib for bile duct cancer?

Ivosidenib has been shown to improve progression-free survival and overall survival in patients with advanced cholangiocarcinoma (a type of bile duct cancer) that have IDH1 mutations. In a phase III study, patients taking Ivosidenib lived longer without their cancer getting worse compared to those who took a placebo. ^{1 2 3 4 5}

Is ivosidenib safe for humans?

Ivosidenib is generally well tolerated in humans, with most side effects being mild, such as diarrhea, nausea, and fatigue. Serious side effects are rare, and the treatment is associated with a low rate of discontinuation due to toxicity, making it a safe option for patients with certain conditions. ^{1 2 5 6 7}

How is the drug Ivosidenib unique in treating bile duct cancer?

Ivosidenib is unique because it specifically targets and inhibits mutant IDH1, a genetic mutation found in some bile duct cancers, which helps slow down cancer progression and improve survival. Unlike standard chemotherapy, it is an oral medication and is particularly beneficial for patients whose cancer has progressed after initial treatments. ^{1 2 3 5 6}

Eligibility Criteria

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 have been treated with an IDH1 inhibitor before.

I have had an organ or tissue transplant.

I've had liver treatments like radiation or ablation within the last 4 weeks.

Timeline

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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 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]

References

1. England pubmed.ncbi.nlm.nih.gov

Ivosidenib in IDH1-mutated cholangiocarcinoma: Clinical evaluation and future directions. [2022]

2. France pubmed.ncbi.nlm.nih.gov

Ivosidenib: A Review in Advanced Cholangiocarcinoma. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Ivosidenib Boosts OS in Cholangiocarcinoma. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

IDH Signalling Pathway in Cholangiocarcinoma: From Biological Rationale to Therapeutic Targeting. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Ivosidenib: an investigational drug for the treatment of biliary tract cancers. [2021]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Clinical Utility of Ivosidenib in the Treatment of IDH1-Mutant Cholangiocarcinoma: Evidence To Date. [2023]

7. France 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. [2022]