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Alternating Chemo-immunotherapy and FGFR Inhibitor for FGFR-positive Biliary or Cholangiocarcinoma

ConditionsLocally Advanced Ampulla of Vater CarcinomaLocally Advanced Biliary Tract CarcinomaLocally Advanced Extrahepatic CholangiocarcinomaLocally Advanced Gallbladder CarcinomaLocally Advanced Intrahepatic CholangiocarcinomaMetastatic Ampulla of Vater CarcinomaMetastatic Biliary Tract CarcinomaMetastatic Extrahepatic CholangiocarcinomaMetastatic Gallbladder CarcinomaMetastatic Intrahepatic CholangiocarcinomaStage III Ampulla of Vater Cancer AJCC v8Stage III Distal Bile Duct Cancer AJCC v8Stage III Gallbladder Cancer AJCC v8Stage III Intrahepatic Cholangiocarcinoma AJCC v8Stage IV Ampulla of Vater Cancer AJCC v8Stage IV Distal Bile Duct Cancer AJCC v8Stage IV Gallbladder Cancer AJCC v8Stage IV Intrahepatic Cholangiocarcinoma AJCC v8Unresectable Ampulla of Vater CarcinomaUnresectable Biliary Tract CarcinomaUnresectable Extrahepatic CholangiocarcinomaUnresectable Gallbladder CarcinomaUnresectable Intrahepatic Cholangiocarcinoma
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorOhio State University Comprehensive Cancer Center

About this trial

This phase II trial tests how well giving gemcitabine, cisplatin and durvalumab alternating with pemigatinib for the treatment of biliary tract cancer with FGFR2 alterations that cannot be removed by surgery (unresectable), that has spread to nearby tissue or lymph nodes (locally advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic). Gemcitabine is a chemotherapy drug that blocks the cells from making DNA and may kill cancer cells. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of cancer cells. Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Pemigatinib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal FGFR protein that signals cancer cells to multiply. This may help keep cancer cells from growing and may kill them. Giving gemcitabine, cisplatin and durvalumab alternating with pemigatinib may work well for the treatment of unresectable, locally advanced or metastatic biliary tract cancer with FGFR2 alterations.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Adults 18 years of age or older with histologically or cytologically confirmed unresectable locally advanced or metastatic carcinoma of the biliary tract, including intrahepatic and extrahepatic cholangiocarcinoma, gallbladder, and ampulla of Vater, at the time of diagnosis

Patients must have tumors classified as having FGFR2 gene fusion/rearrangements or other gain-of function alterations involved in FGFR as detected by any analytically validated, Clinical Laboratory Improvement Act (CLIA)-certified molecular testing, including commercial tests (Foundation Medicine, Caris, Tempus, Guardant360, and others) or other platforms of next generation sequencing. Gene rearrangements are structural variants that can include inversions, translocations, duplications, and truncations. In addition, all patients will have tumor specimens sent and stored centrally

Patients are permitted to have received one 21-day or 28-day cycle of either gemcitabine/cisplatin or gemcitabine/cisplatin with immunotherapy (either durvalumab or pembrolizumab) prior to inclusion in trial, and this will count as the first cycle in the schematic

One or more measurable lesions per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v 1.1)

Disqualifiers

Received any definitive radiotherapy, targeted therapy, immunotherapy, or any investigational therapies within 13 days of the first study drug administration. Patients are permitted to have received one 21- or 28-day cycle of either gem/cis or gemcitabine/cisplatin/durvalumab prior to inclusion in trial, and this will count as the first cycle in the schematic. Localized palliative radiation therapy (should not include radiation to target lesions) and ongoing bisphosphonates and denosumab, are permitted

Patients who have not recovered from reversible toxicity of prior anti-tumor therapy (except toxicities which are not clinically significant such as alopecia, grade 0-2 neuropathy)

Patients who received prior FGFR-targeted therapy

Within 2 weeks before the first dose of study drug, the subject's calcium and phosphate level continuing to exceed the ULN despite medical treatment

Trial design

Design model

Single group

Treatments tested in this trial

  • Biospecimen Collection

    Procedure/Surgery

    Undergo blood sample collection

  • Cisplatin

    Drug

    Given IV

  • Computed Tomography

    Procedure/Surgery

    Undergo CT scan

  • Durvalumab

    Biological/Vaccine

    Given IV

  • Gemcitabine

    Drug

    Given IV

  • Magnetic Resonance Imaging

    Procedure/Surgery

    Undergo MRI

  • Pemigatinib

    Drug

    Given PO

  • Survey Administration

    Other intervention

    Ancillary studies

Treatment groups

29 Participants
are divided into 1 treatment group
Group A: Treatment (chemoimmunotherapy, FGFRi cycles)Experimental treatment 8 interventions

Trial outcomes

Primary outcomes

1

Overall survival (OS)

Defined as the date of start of treatment to the date of death due to any cause. Will be analyzed using the Kaplan Meier method. Survival rate at 12 months and median OS will be estimated along with 95% confidence intervals from the Kaplan Meier distribution.

Time frame
At 12 months

Secondary outcomes

1

Overall response rate (ORR)

Defined as complete response (CR) + partial response (PR). Assessed by investigator as per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. The estimated ORR will be presented along with the corresponding 95% confidence interval for each cohort, based on a binomial distribution.

Time frame
Up to 5 years
2

Disease control rate

Defined as CR + PR + stable disease. Assessed by investigator as per RECIST v 1.1.

Time frame
Up to 5 years
3

Duration of response

Time frame
Up to 5 years
4

Duration of therapy (DOT)

The median DOT will be presented along with the corresponding 95% confidence interval for each cohort, based on a binomial distribution.

Time frame
From start of cyclical therapy to termination of cyclical therapy, up to 5 years

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Ohio State University Comprehensive Cancer Center

Lead sponsor

Incyte Corporation

Collaborator

Source ClinicalTrials.gov
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