NCT04088188

Gemcitabine and Cisplatin With Ivosidenib or Pemigatinib for the Treatment of Unresectable or Metastatic Cholangiocarcinoma

A Phase I, Multi-Center, Open Label, Dose De-Escalation and Expansion Study of Gemcitabine and Cisplatin With AG120 or Pemigatinib for Advanced Cholangiocarcinoma

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 8 (actual)
• Sponsor: Academic and Community Cancer Research United · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I 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). Chemotherapy drugs, 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.

Detailed description

PRIMARY OBJECTIVE: I. To evaluate the safety, tolerability, maximum tolerated dose (MTD) and/or recommended phase 2 dose, gemcitabine and cisplatin in combination with either ivosidenib or pemigatinib. SECONDARY OBJECTIVES: I. To evaluate median and progression free survival (PFS) for 6 months per investigator assessment. II. To evaluate the rate of overall survival (OS) in patients treated with gemcitabine and cisplatin in combination with either ivosidenib or pemigatinib. III. To describe the overall toxicity and adverse events profile associated with gemcitabine and cisplatin in combination with either ivosidenib or pemigatinib. IV. To determine the best response profile per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria in patients treated with gemcitabine and cisplatin in combination with either ivosidenib or pemigatinib. CORRELATIVE RESEARCH OBJECTIVE: I. To measure plasma 2-hydroxglutarate (2-HG) levels =\< 21 days prior to registration and at cycle 4 day 1 (+/- 2 days). OUTLINE: This is a dose de-escalation study. Patients are assigned to 1 of 2 arms. ARM A (IDH1 GENE MUTATION): Patients receive ivosidenib orally (PO) on days 1-21, cisplatin intravenously (IV) on days 1 and 8, and gemcitabine IV on days 1 and 8. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. ARM B (FGFR2 GENE ALTERATION): Patients receive pemigatinib PO on days 1-21, cisplatin IV on days 1 and 8, and gemcitabine IV on days 1 and 8. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days and then every 6 months for up to 3 years.

Conditions

• Advanced Cholangiocarcinoma
• Metastatic Cholangiocarcinoma
• Unresectable Cholangiocarcinoma

Interventions

Type	Name	Description
DRUG	Cisplatin	Given IV
DRUG	Gemcitabine	Given IV
DRUG	Ivosidenib	Given PO
DRUG	Pemigatinib	Given PO

Timeline

• Start date: 2021-01-25
• Primary completion: 2023-12-01
• Completion: 2023-12-01
• First posted: 2019-09-12
• Last updated: 2024-05-06
• Results posted: 2024-05-02

Locations

7 sites across 1 country: United States

Regulatory

• FDA-regulated drug study