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A Phase II, Single Arm Study of BGJ398 in Patients With Advanced Cholangiocarcinoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02150967
Recruitment Status : Completed
First Posted : May 30, 2014
Results First Posted : July 15, 2022
Last Update Posted : July 15, 2022
Sponsor:
Collaborator:
Helsinn Healthcare SA
Information provided by (Responsible Party):
QED Therapeutics, Inc.

Brief Summary:
This is a multi-center, open label, single arm phase II study evaluating BGJ398 (infigratinib) anti-tumor activity in advanced or metastatic cholangiocarcinoma patients with fibroblast growth factor receptor (FGFR) genetic alterations.

Condition or disease Intervention/treatment Phase
Advanced Cholangiocarcinoma FGFR2 Gene Mutation Drug: BGJ398 (infigratinib) Phase 2

Detailed Description:

Adult patients with histologically or cytologically confirmed advanced or metastatic cholangiocarcinoma with FGFR2 gene fusions or translocations or other FGFR genetic alterations have been enrolled. Subjects must have received at least one prior regimen containing gemcitabine with or without cisplatin for advanced/metastatic disease. Subjects should have had evidence of progressive disease following their prior regimen or if prior treatment was discontinued due to toxicity must have continued evidence of measurable disease. Up to approximately 160 adult patients over age 18, both male and female were planned for enrollment.

Three cohorts of subjects comprise the study population:

Cohort 1: subjects with FGFR2 gene fusions (ie, fusions or rearrangements [formerly translocations]) and those with other FGFR genetic alterations (ie, nonfusion; these subjects were enrolled before protocol amendment [PA] 2).

Cohort 2: subjects with FGFR genetic alterations other than FGFR2 gene fusions or rearrangements.

Cohort 3: subjects with FGFR2 gene fusions or rearrangements who have received a prior FGFR inhibitor.

Note: Cohorts 2 and 3 were added at PA 4 to support exploratory objectives of the study. These cohorts are not part of the primary efficacy analysis reported in this disclosure.

All subjects received oral BGJ398 (infigratinib), once-daily, on a three weeks on (21 days), one week off (7 days) schedule. One treatment cycle consists of 28 days.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 143 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Multicenter, Single Arm Study of Oral BGJ398 in Adult Patients With Advanced or Metastatic Cholangiocarcinoma With FGFR2 Gene Fusions or Other FGFR Genetic Alterations Who Failed or Are Intolerant to Platinum-based Chemotherapy
Actual Study Start Date : July 23, 2014
Actual Primary Completion Date : March 1, 2021
Actual Study Completion Date : February 7, 2022


Arm Intervention/treatment
Experimental: BGJ398 (infigratinib)
To estimate the anti-tumor activity of BGJ398 (infigratinib)
Drug: BGJ398 (infigratinib)
Capsule for oral use




Primary Outcome Measures :
  1. Overall Response Rate (ORR) as Assessed by Blinded Independent Central Imaging Review (BICR) [ Time Frame: Analysis was conducted when all subjects in Cohort 1 had the opportunity to be followed for at least 10 months after their initial exposure to infigratinib. Data cutoff 01 March 2021. ]

    ORR is defined as the percentage (%) of subjects with a best overall response of Complete Response (CR) or Partial Response (PR), as per Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1, evaluated by computed tomography (CT) or magnetic resonance imaging (MRI) scans every 28 days.

    RECIST (v1.1) response criteria were as follows:

    CR: disappearance of all target lesions. Any pathological lymph node (whether target or non-target) must have reduction in short axis to <10 mm.

    PR: at least a 30% decrease from baseline in the sum of diameters of all target lesions.

    Note: The primary efficacy outcome measures were prespecified only for Cohort 1 (FGFR fusions).

    Cohort 1 (Other FGFR alterations) was not the primary analysis population, thus efficacy results for this cohort are not reported.



Secondary Outcome Measures :
  1. Overall Response Rate (ORR) as Assessed by the Investigator [ Time Frame: Analysis conducted when all subjects in Cohort 1 had the opportunity to be followed for at least 10 months after their initial exposure to infigratinib. Data cutoff 01 March 2021. ]

    ORR is defined as the percentage (%) of subjects with a best overall response of CR or PR, evaluated by CT or MRI scans every 28 days.

    RECIST (v1.1) response criteria were as follows:

    CR: disappearance of all target lesions. Any pathological lymph node (whether target or non-target) must have reduction in short axis to <10 mm.

    PR: at least a 30% decrease from baseline in the sum of diameters of all target lesions.

    Note: The primary efficacy outcome measures were prespecified only for Cohort 1 (FGFR fusions).

    Cohort 1 (Other FGFR alterations) was not the primary analysis population, thus efficacy results for this cohort are not reported.


  2. Best Overall Response (BOR) [ Time Frame: Analysis conducted when all subjects in Cohort 1 had the opportunity to be followed for at least 10 months after their initial exposure to infigratinib. Data cutoff 01 March 2021. ]

    BOR is defined as the best overall response a subject achieved during the study before any subsequent antineoplastic therapy. The endpoint is summarized for the rate of BOR of CR, PR, progressive disease (PD), and stable disease (SD), evaluated by CT or MRI scans every 28 days.

    RECIST (v1.1) response criteria were as follows:

    CR: disappearance of all target lesions. Any pathological lymph node (whether target or non-target) must have reduction in short axis to <10 mm.

    PR: at least a 30% decrease from baseline in the sum of diameters of all target lesions.

    PD: at least a 20% increase in the sum of diameters of all target lesions from that of the smallest sum on study and an absolute increase in target lesion of at least 5mm.

    SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of diameters while on study.

    Note: Primary efficacy outcome measures were prespecified only for Cohort 1 (FGFR fusions).


  3. Disease Control Rate (DCR) [ Time Frame: Analysis conducted when all subjects in Cohort 1 had the opportunity to be followed for at least 10 months after their initial exposure to infigratinib. Data cutoff 01 March 2021. ]

    DCR is the percentage (%) of subjects with a BOR of CR, PR, or SD, evaluated by CT or MRI scans every 28 days.

    Results are based on both BICR and on Investigator assessment.

    RECIST (v1.1) response criteria were as follows:

    CR: disappearance of all target lesions. Any pathological lymph node (whether target or non-target) must have reduction in short axis to <10 mm.

    PR: at least a 30% decrease from baseline in the sum of diameters of all target lesions.

    SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of diameters while on study.

    Note: The primary efficacy outcome measures were prespecified only for Cohort 1 (FGFR fusions).

    Cohort 1 (Other FGFR alterations) was not the primary analysis population, thus efficacy results for this cohort are not reported.


  4. Progression-Free Survival (PFS) [ Time Frame: Analysis conducted when all subjects in Cohort 1 had the opportunity to be followed for at least 10 months after their initial exposure to infigratinib. Data cutoff 01 March 2021. ]

    PFS was calculated as the number of months from the first dose of study drug to the first documented progression or death due to any cause, whichever occurred earlier. Subjects without an assessment of progression or death were censored at the last adequate tumor assessment. For subjects who had an event after ≥2 missed visits, the subject was censored at the last adequate tumor assessment before the missing visit.

    Disease progression was assessed per RECIST (v1.1) and defined as at least a 20% increase in the sum of diameters of all target lesions from that of the smallest sum on study and an absolute increase in target lesion of at least 5mm.

    Results are based on both BICR and on Investigator assessment.

    Note: The primary efficacy outcome measures were prespecified only for Cohort 1 (FGFR fusions).

    Cohort 1 (Other FGFR alterations) was not the primary analysis population, thus efficacy results for this cohort are not reported.


  5. Overall Survival (OS) [ Time Frame: Analysis conducted when all subjects in Cohort 1 had the opportunity to be followed for at least 10 months after their initial exposure to infigratinib. Data cutoff 01 March 2021. ]

    OS was defined as the time (months) from the date of start of treatment to the date of death due to any cause.

    Note: The primary efficacy outcome measures were prespecified only for Cohort 1 (FGFR fusions).

    Cohort 1 (Other FGFR alterations) was not the primary analysis population, thus efficacy results for this cohort are not reported.


  6. Duration of Response (DOR) [ Time Frame: Analysis conducted when all subjects in Cohort 1 had the opportunity to be followed for at least 10 months after their initial exposure to infigratinib. Data cutoff 01 March 2021. ]

    DOR is defined as the time (months) from the initial response to the time of the event; defined as the first documented progression or death due to any cause, whichever was earlier.

    Note that results are based on a subgroup of subjects with confirmed responses (CR or PR) as assessed by BICR or by the Investigator.

    RECIST (v1.1) response criteria was as follows:

    CR: disappearance of all target lesions. Any pathological lymph node (whether target or non-target) must have reduction in short axis to <10 mm.

    PR: at least a 30% decrease from baseline in the sum of diameters of all target lesions.

    Note: The primary efficacy outcome measures were prespecified only for Cohort 1 (FGFR fusions).

    Cohort 1 (Other FGFR alterations) was not the primary analysis population, thus efficacy results for this cohort are not reported.


  7. Response Onset [ Time Frame: Analysis conducted when all subjects in Cohort 1 had the opportunity to be followed for at least 10 months after their initial exposure to infigratinib. Data cutoff 01 March 2021. ]

    Response onset was defined as the time (months) from the first study treatment administration date to the initial response.

    Note that results are based on a subgroup of subjects with confirmed responses (CR or PR) as assessed by BICR or by the Investigator.

    RECIST (v1.1) response criteria was as follows:

    CR: disappearance of all target lesions. Any pathological lymph node (whether target or non-target) must have reduction in short axis to <10 mm.

    PR: at least a 30% decrease from baseline in the sum of diameters of all target lesions.

    Note: The primary efficacy outcome measures were prespecified only for Cohort 1 (FGFR fusions).

    Cohort 1 (Other FGFR alterations) was not the primary analysis population, thus efficacy results for this cohort are not reported.



Other Outcome Measures:
  1. Growth Modulation Index (GMI) [ Time Frame: Analysis conducted when all subjects in Cohort 1 had the opportunity to be followed for at least 10 months after their initial exposure to infigratinib. Data cutoff 01 March 2021. ]

    The GMI is defined as the ratio of PFS (months) during treatment with infigratinib relative to the time (months) to progression (TTP) during treatment with last prior line of therapy.

    Subjects served as their own control.

    Results are provided for both BICR and Investigator assessment.

    Note: The primary efficacy outcome measures were prespecified only for Cohort 1 (FGFR fusions).

    Cohort 1 (Other FGFR alterations) was not the primary analysis population, thus efficacy results for this cohort are not reported.




Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

- Adult patients with histologically or cytologically confirmed cholangiocarcinoma at the time of diagnosis.

Patients with cancers of the gallbladder or ampulla of Vater are not eligible.

- Patients must have received at least one prior regimen containing gemcitabine with or without cisplatin for advanced/ metastatic disease. Patient should have evidence of progressive disease following prior regimen, or if prior treatment discontinued due to toxicity must have continued evidence of measurable or evaluable disease.

Exclusion criteria:

  • Prior or current treatment with a MEK inhibitor (all Cohorts), BGJ398 (infigratinib) (all Cohorts), or selective FGFR inhibitor (Cohorts 1 and 2 only).
  • insufficient organ function

    • Absolute Neutrophil Count (ANC) < 1,000/mm3 [1.0 x 10^9/L]
    • Platelets < 75,000/mm3 [75 x 10^9/L]
    • Hemoglobin < 109.0 g/dL
    • Total bilirubin > 1.5x upper limit of normal (ULN)
    • Aspartate aminotransferase/glutamic oxaloacetic transaminase (AST/SGOT) and alanine aminotransferase/glutamic pyruvic transaminase (ALT/SGPT) > 2.5x ULN (AST and ALT > 5x ULN in the presence of liver metastases)
    • Serum creatinine > 1.5x ULN and a calculated or measured creatinine clearance < 45 mL/min
    • Inorganic phosphorus outside of normal limits
    • Total and ionized serum calcium outside of normal limits

Other protocol-defined inclusion/exclusion criteria may apply.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02150967


Locations
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United States, Arizona
QED Investigative Site
Phoenix, Arizona, United States, 85054
United States, California
QED Investigative Site
Los Angeles, California, United States, 90033
QED Investigative Site
Los Angeles, California, United States, 90095
QED Investigative Site
San Francisco, California, United States, 94158
United States, Massachusetts
QED Investigative Site
Boston, Massachusetts, United States, 02114
United States, Michigan
QED Investigative Site
Detroit, Michigan, United States, 48201
United States, New York
QED Investigative Site
New York, New York, United States, 10016
QED Investigative Site
New York, New York, United States, 10029
QED Investigative Site
New York, New York, United States, 10065
United States, Ohio
QED Investigative Site
Columbus, Ohio, United States, 43221
United States, Texas
QED Investigative Site
Houston, Texas, United States, 77030-4009
Belgium
QED Investigative Site
Brussels, Belgium, 1200
QED Investigative Site
Leuven, Belgium, 3000
Germany
QED Investigative Site
Koeln, Nordrhein-Westfalen, Germany, 50937
QED Investigative Site
Heidelberg, Germany, 69120
QED Investigative Site
Tuebingen, Germany
Italy
QED Investigative Site
Ancona, AN, Italy, 60126
QED Investigative Site
Milano, MI, Italy, 20132
QED Investigative Site
Roma, RM, Italy, 00168
Korea, Republic of
QED Investigative Site
Seoul, Korea, Korea, Republic of, 03080
QED Investigative Site
Seoul, Korea, Korea, Republic of, 06351
Russian Federation
QED Investigative Site
Moscow, Russian Federation, 125367
QED Investigative Site
Volzhskiy, Russian Federation, 404133
Singapore
QED Investigative Site
Singapore, Singapore, 119228
QED Investigative Site
Singapore, Singapore, 169610
Spain
QED Investigative Site
Barcelona, Spain, 8035
QED Investigative Site
Barcelona, Spain, 8908
QED Investigative Site
Madrid, Spain, 28050
Taiwan
QED Investigative Site
Taipei, Taiwan ROC, Taiwan, 10041
QED Investigative Site
Zhunan, Taiwan, 35053
Thailand
QED Investigative Site
Khon Kaen, THA, Thailand, 40002
QED Investigative Site
Bangkok, Thailand, 10330
QED Investigative Site
Bangkok, Thailand, 10400
United Kingdom
QED Investigative Site
Bebington, United Kingdom, CH63 4JY
QED Investigative Site
Birmingham, United Kingdom, B15 2TH
QED Investigative Site
Manchester, United Kingdom, M20 4BX
QED Investigative Site
Nottingham, United Kingdom, NG5 1PB
Sponsors and Collaborators
QED Therapeutics, Inc.
Helsinn Healthcare SA
Investigators
Layout table for investigator information
Study Director: QED Therapeutics QED Therapeutics
  Study Documents (Full-Text)

Documents provided by QED Therapeutics, Inc.:
Study Protocol  [PDF] January 15, 2020
Statistical Analysis Plan  [PDF] May 13, 2020

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: QED Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT02150967    
Other Study ID Numbers: CBGJ398X2204
2013-005085-19 ( EudraCT Number )
First Posted: May 30, 2014    Key Record Dates
Results First Posted: July 15, 2022
Last Update Posted: July 15, 2022
Last Verified: June 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by QED Therapeutics, Inc.:
cholangiocarcinoma,
FGFR2 gene fusion,
FGFR genetic alteration
Additional relevant MeSH terms:
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Cholangiocarcinoma
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Infigratinib
Antineoplastic Agents