This trial studies the side effects and best dose of gemcitabine and cisplatin when given together with ivosidenib or pemigatinib in treating patients with cholangiocarcinoma that cannot be removed with surgery (unresectable) or has spread to other places in the body (metastatic). Drugs used in chemotherapy, such as gemcitabine and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Ivosidenib and pemigatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving gemcitabine and cisplatin with ivosidenib or pemigatinib may work better in treating patients with cholangiocarcinoma compared to gemcitabine and cisplatin alone.
Name: Cisplatin
Name: Gemcitabine
Name: Gemcitabine Hydrochloride
Name: Ivosidenib
Name: Pemigatinib
Description: A significant toxicity is defined as a dose limiting toxicity that is possibly, probably, or definitely related to treatment (ivosidenib or pemigatinib in combination with cisplatin and gemcitabine). Toxicities will be assessed using Common Terminology Criteria for Adverse Events.
Measure: Incidence of significant toxicities Time: At 27 weeksDescription: Overall survival is defined as the length of time from start of study therapy to death due to any cause. The distribution of overall survival for both arms of the study will be estimated separately using the Kaplan-Meier method.
Measure: Overall survival Time: From start of study therapy to death due to any cause, assessed up to 3 yearsDescription: Progression free survival time is defined as the time from the start of study therapy to documentation of disease progression. Patients who die without documentation of progression will be considered to have had tumor progression at the time of death. Patients who are still alive and have not progressed will be censored for progression at the time of the last disease evaluation. The time-to-progression distribution will be estimated separately for both arms, using the Kaplan-Meier method.
Measure: Progression free survival Time: From the start of study therapy to documentation of disease progression, assessed up to 3 yearsDescription: The number and severity of all adverse events (overall, by dose-level, and by tumor group) will be tabulated and summarized in this patient population. The grade 3+ adverse events will also be described and summarized in a similar fashion.
Measure: Incidence of adverse events Time: Up to 3 yearsDescription: The term toxicity is defined as adverse events that are classified as either possibly, probably, or definitely related to study treatment. Non-hematologic toxicities will be evaluated via the ordinal Common Terminology Criteria (CTC) standard toxicity grading. Hematologic toxicity measures of thrombocytopenia, neutropenia, and leukopenia will be assessed using continuous variables as the outcome measures (primarily nadir) as well as categorization via CTC standard toxicity grading. Overall toxicity incidence as well as toxicity profiles by dose level, patient and tumor site will be explored and summarized. Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.
Measure: Incidence of toxicities Time: Up to 3 yearsDescription: Best Response is defined to be the best objective status recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The patient?s best response assignment will depend on the achievement of both measurement and confirmation criteria. Response Evaluation Criteria in Solid Tumors 1.1 criteria will be used for tumor evaluation and patients will be re-evaluated every prior to treatment in cycle 3 and then in odd subsequent cycles. Responses will be summarized by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease in this patient population (overall and by tumor group).
Measure: Best response Time: From the start of the treatment until disease progression/recurrence, assessed up to 3 yearsAllocation: Non-Randomized
Parallel Assignment
There is one SNP
Prior systemic adjuvant chemotherapy is allowed as long as there was no evidence of recurrence within 6 months of completing the adjuvant therapy - Molecular testing result from Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory (using fresh tumor biopsy or most recent banked tumor tissue available) confirming that the tumor tissue has at least one of the following: - IDH1 gene mutation (R132C/L/G/H/S mutation) - FGFR1, FGFR2, or FGFR3 gene alteration - Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 - Life expectancy >= 3 months - At least one evaluable and measurable lesion by RECIST criteria prior to beginning chemotherapy with gemcitabine and cisplatin - NOTE: Subjects who have received prior local therapy (including but not limited to embolization, chemoembolization, radiofrequency ablation, hepatic arterial infusion, or radiation therapy) are eligible provided measurable disease falls outside of the treatment - Recovered from toxicities associated with prior anticancer therapy to baseline unless stabilized under medical management - Absolute neutrophil count >= 1,500/mm^3 (obtained =< 21 days prior to registration) - Platelet count >= 100,000/mm^3 (obtained =< 21 days prior to registration) - Hemoglobin >= 8 g/dL (obtained =< 21 days prior to registration) - Serum total bilirubin =< 2.0 x upper limit of normal (ULN), unless considered due to Gilbert's disease. --- R132C ---