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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
EU CTIS ID: 2024-514261-19-00
What this study is testing
Safety Lead-in Phase: To assess the safety and tolerability of ivosidenib in combination with durvalumab and gemcitabine/cisplatin as first-line therapy in participants with locally advanced, unresectable or metastatic CCA harboring on isocitrate deshydrogenase 1 (IDH1) mutation. To determine the recommended combination dose (RCD) of ivosidenib in combination with durvalumab and gemcitabine/cisplatin as first-line therapy. Expansion Phase: To assess the clinical activity of ivosidenib in combination with durvalumab and gemcitabine/cisplatin as first-line therapy using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
- Phase I and Phase II (Integrated)- Other
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- Have a histopathological confirmed diagnosis consistent with locally advanced unresectable or metastatic cholangiocarcinoma
- Have documented IDH1 gene-mutated CCA based on local testing (R132C/L/G/H/S mutation variants tested).
- Have at least one evaluable and measurable lesion as defined by RECIST v1.1.
- Have adequate bone marrow function as evidenced by: - Absolute neutrophil count ≥ 1,500/mm3 or 1.5 ×109/L - Hemoglobin ≥ 9 g/dL - Platelet count ≥ 100,000/mm3 or 100 × 109/L
- Have adequate hepatic function as evidenced by: - Serum bilirubin ≤ 1.5 × the upper limit of normal (ULN); this will not apply to participants with confirmed Gilbert’s syndrome. Any clinically significant biliary obstruction should be resolved before randomization - Aspartate aminotransferase (AST), and alanine aminotransferase (ALT) ≤ 2.5 × ULN; for participants with hepatic metastases, ALT and AST ≤ 5.0 × ULN
- Have adequate renal function, defined as: creatinine clearance > 50 mL/min as calculated by Cockcroft-Gault formula (using actual body weight): Creatine CL (mL/min)= (140 − Age) × (weight in kg) × (0.85 if female)/72 × serum creatinine (mg/dL)
You likely can't join if
- Received treatment for locally advanced, unresectable or metastatic disease with the following exceptions: - Treatment with up to one cycle of durvalumab plus gemcitabine/cisplatin treatment is permitted before initiation of study treatment (Cycle 1 Day 1) and if 1 cycle of durvalumab plus gemcitabine/cisplatin was given prior to C1D1, participants may receive up to 7 cycles of durvalumab/gemcitabine/cisplatin with ivosidenib on study. 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. - Participants 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).
- 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, or one prior cycle allowance in aforementioned criteria.
- Unresolved Grade ≥2 adverse events from a previous anticancer therapy (e.g. neuropathy), with the exception of alopecia and vitiligo and the laboratory values listed in the inclusion criteria. - Participants with irreversible toxicity not reasonably expected to be exacerbated by treatment with ivosidenib may be included only after consultation with the medical monitor
- Participation in another interventional study at the same time or within 14 days prior to the first study medication (triple combination treatment) administration.
- Active or prior documented autoimmune or inflammatory disorders including: - Inflammatory bowel disease (e.g., colitis or Crohn’s disease) - Diverticulitis (with the exception of diverticulosis) - Systemic lupus erythematosus - Sarcoidosis syndrome - Wegener syndrome (granulomatosis with polyangiitis, Graves’ disease, rheumatoid arthritis, hypophysitis, uveitis, etc.) Note: in cases with no active disease for ≥ 5 years, patients may be considered for inclusion if approved by the Medical Monitor.
- Participants with the following conditions are eligible for the study: - chronic skin condition that does not require systemic therapy - vitiligo - alopecia - hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement therapy - unmedicated celiac disease that is controlled by diet
See the full eligibility criteria
Who can join
- Have a histopathological confirmed diagnosis consistent with locally advanced unresectable or metastatic cholangiocarcinoma
- Have documented IDH1 gene-mutated CCA based on local testing (R132C/L/G/H/S mutation variants tested).
- Have at least one evaluable and measurable lesion as defined by RECIST v1.1.
- Have adequate bone marrow function as evidenced by: - Absolute neutrophil count ≥ 1,500/mm3 or 1.5 ×109/L - Hemoglobin ≥ 9 g/dL - Platelet count ≥ 100,000/mm3 or 100 × 109/L
- Have adequate hepatic function as evidenced by: - Serum bilirubin ≤ 1.5 × the upper limit of normal (ULN); this will not apply to participants with confirmed Gilbert’s syndrome. Any clinically significant biliary obstruction should be resolved before randomization - Aspartate aminotransferase (AST), and alanine aminotransferase (ALT) ≤ 2.5 × ULN; for participants with hepatic metastases, ALT and AST ≤ 5.0 × ULN
- Have adequate renal function, defined as: creatinine clearance > 50 mL/min as calculated by Cockcroft-Gault formula (using actual body weight): Creatine CL (mL/min)= (140 − Age) × (weight in kg) × (0.85 if female)/72 × serum creatinine (mg/dL)
What rules you out
- Received treatment for locally advanced, unresectable or metastatic disease with the following exceptions: - Treatment with up to one cycle of durvalumab plus gemcitabine/cisplatin treatment is permitted before initiation of study treatment (Cycle 1 Day 1) and if 1 cycle of durvalumab plus gemcitabine/cisplatin was given prior to C1D1, participants may receive up to 7 cycles of durvalumab/gemcitabine/cisplatin with ivosidenib on study. 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. - Participants 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).
- 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, or one prior cycle allowance in aforementioned criteria.
- Unresolved Grade ≥2 adverse events from a previous anticancer therapy (e.g. neuropathy), with the exception of alopecia and vitiligo and the laboratory values listed in the inclusion criteria. - Participants with irreversible toxicity not reasonably expected to be exacerbated by treatment with ivosidenib may be included only after consultation with the medical monitor
- Participation in another interventional study at the same time or within 14 days prior to the first study medication (triple combination treatment) administration.
- Active or prior documented autoimmune or inflammatory disorders including: - Inflammatory bowel disease (e.g., colitis or Crohn’s disease) - Diverticulitis (with the exception of diverticulosis) - Systemic lupus erythematosus - Sarcoidosis syndrome - Wegener syndrome (granulomatosis with polyangiitis, Graves’ disease, rheumatoid arthritis, hypophysitis, uveitis, etc.) Note: in cases with no active disease for ≥ 5 years, patients may be considered for inclusion if approved by the Medical Monitor.
- Participants with the following conditions are eligible for the study: - chronic skin condition that does not require systemic therapy - vitiligo - alopecia - hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement therapy - unmedicated celiac disease that is controlled by diet
- 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.
- Have an active , severe, or uncontrolled active, or acute or chronic infection, are not eligible : - Known co-infection with HBV and HCV, or co-infection with HBV and HDV. HBV, HCV, or HDV positivity is defined as: * HBV positive (presence of HBsAg and/or anti-HBcAb with detectable HBV DNA or HBV RNA) * HCV positive (presence of anti-HCV antibodies or HCV RNA) * HDV positive (presence of anti-HDV antibodies or HDV RNA) - Known Tuberculosis (clinical evaluation includes: clinical history, physical examination and/or radiographic findings, and tuberculosis testing as per local practice) - Known human immunodeficiency virus (clinical evaluation includes: positive HIV 1/2 antibodies)
The study team makes the final eligibility decision.
Where it's taking place
- United States
- Canada
- Japan
- Australia
- Brazil
- Korea, Republic of
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18-64 years, 65+ years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include United States; Canada; Japan; Australia; Brazil; Korea, Republic of. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.