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Futibatinib Vs Gemcitabine-Cisplatin Chemotherapy as 1st-Line Treatment of Patients With Advanced Cholangiocarcinoma (CCA) Harboring FGFR2 Gene Rearrangements

NCT04093362

Description:

The purpose is an open-label, multinational, parallel 2-arm, randomized Phase 3 study evaluating the efficacy and safety of futibatinib versus gemcitabine-cisplatin chemotherapy as first-line treatment of patients with advanced, metastatic, or recurrent unresectable iCCA harboring FGFR2 gene rearrangements

Related Conditions:
  • Intrahepatic Cholangiocarcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Futibatinib Vs Gem-Cis Chemo as 1st-Line Treatment of Patients With Advanced CCA Harboring FGFR2 Gene Rearrangements
  • Official Title: A Phase 3, Open-Label, Randomized Study of Futibatinib Versus Gemcitabine-Cisplatin Chemotherapy as First-Line Treatment of Patients With Advanced Cholangiocarcinoma Harboring FGFR2 Gene Rearrangements FOENIX-CCA3

Clinical Trial IDs

  • ORG STUDY ID: FOENIX-MCCA3 TAS-120-301
  • NCT ID: NCT04093362

Conditions

  • Advanced Cholangiocarcinoma
  • FGFR2 Gene Rearrangements

Interventions

DrugSynonymsArms
TAS-120FutibatinibTAS-120
Cisplatin/GemcitabineCisplatin/Gemcitabine

Purpose

The purpose is an open-label, multinational, parallel 2-arm, randomized Phase 3 study evaluating the efficacy and safety of futibatinib versus gemcitabine-cisplatin chemotherapy as first-line treatment of patients with advanced, metastatic, or recurrent unresectable iCCA harboring FGFR2 gene rearrangements

Detailed Description

      Study TAS-120-301 is an open-label, multinational, parallel 2-arm, randomized Phase 3 study
      evaluating the efficacy and safety of futibatinib versus gemcitabine-cisplatin chemotherapy
      as first-line treatment of patients with advanced, metastatic, or recurrent unresectable iCCA
      harboring FGFR2 gene rearrangements. Eligible patients will be randomized on a 1:1 basis to
      the following study arms:

        -  Experimental Arm: Patients will receive futibatinib at an oral dose of 20 mg,
           administered daily (QD) on every day of a 21-day cycle.

        -  Control Arm: On Days 1 and 8 of a 21-day cycle, patients will receive:

             -  Cisplatin 25 mg/m2 in 1000 mL 0.9% saline by intravenous (I.V.) infusion over 1
                hour, followed by 500 mL 0.9% saline over 30 minutes; and

             -  Gemcitabine 1000 mg/m2 in 250-500 mL 0.9% saline by I.V. infusion over 30 minutes,
                beginning after completion of the cisplatin and saline infusions.

      Patients in the Experimental Arm may continue to receive continuous futibatinib until
      documentation of progressive disease (PD) per RECIST 1.1, or until other withdrawal criteria
      are met, whichever comes first. However, treatment may continue following PD per RECIST 1.1
      if the patient is clinically stable and is considered by the Investigator to be deriving
      continued clinical benefit from futibatinib.

      Patients in the Control Arm may receive gemcitabine-cisplatin chemotherapy for up to 8 cycles
      or until PD or other withdrawal criteria are met, whichever comes first. Patients who
      discontinue gemcitabine-cisplatin due to documented disease progression (by ICR) may receive
      treatment with futibatinib ("crossover"), if medically appropriate in the opinion of the
      Investigator and if criteria for futibatinib treatment are met.
    

Trial Arms

NameTypeDescriptionInterventions
TAS-120ExperimentalTAS-120 tablets, oral; 28-day cycle
  • TAS-120
Cisplatin/GemcitabineActive Comparator• On Days 1 and 8 of a 21-day cycle, patients will receive: Cisplatin 25 mg/m2 in 1000 mL 0.9% saline by intravenous (I.V.) infusion over 1 hour, followed by 500 mL 0.9% saline over 30 minutes; and Gemcitabine 1000 mg/m2 in 250-500 mL 0.9% saline by I.V. infusion over 30 minutes, beginning after completion of the cisplatin and saline infusions.
  • Cisplatin/Gemcitabine

Eligibility Criteria

        Inclusion Criteria:

        A patient must meet all of the following inclusion criteria to be eligible for enrollment
        in this study:

          1. Provide written informed consent.

          2. Is >=18 years of age (or meets the country's regulatory definition for legal adult
             age).

          3. The patient has histologically confirmed, locally advanced, or metastatic, or
             recurrent unresectable iCCA harboring FGFR2 gene rearrangements based on testing
             performed by the designated central laboratory.

          4. Patient has radiographically measurable disease per RECIST 1.1.

          5. Patients who have received treatment for locally advanced disease (for example,
             trans-arterial chemoembolization, selective internal radiation therapy, external beam
             radiation) must have evidence of radiographic progression with measurable disease
             outside the previously-treated lesions.

          6. Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1.

          7. Adequate organ function as defined by the following criteria:

               -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 ×upper
                  limit of normal (ULN); if liver function abnormalities are due to underlying
                  liver metastasis, AST and ALT ≤ 5 × ULN.

               -  Total bilirubin ≤ 1.5 × ULN, or ≤ 3.0 × ULN for patients with Gilbert's syndrome.

               -  White Blood Count (WBC) ≥ 2000/mm3 (≥ 2.0 × 109/L)

               -  Absolute neutrophil count (ANC) ≥ 1000/mm3 (ie, ≥ 1.0 × 109/L by International
                  Units [IU])

               -  Platelet count ≥ 100,000/mm3 (IU: ≥ 100 × 109/L)

               -  Hemoglobin ≥ 9.0 g/dL

               -  Phosphorus ≤ 1.5 × ULN

               -  Creatinine clearance: ≥ 60 mL/min

          8. Women of child-bearing potential (WOCBP) must have a negative serum pregnancy test
             within 7 days prior to administration of the first dose of futibatinib. Female
             patients are not considered to be of child bearing potential if they have a history of
             hysterectomy or are post menopausal defined as no menses for 12 months without an
             alternative medical cause. Both males and females of reproductive potential must agree
             to use effective birth control during the study prior to the first dose and for 6
             months after the last dose.

          9. Willing and able to comply with scheduled visits and study procedures.

        Exclusion Criteria:

        A patient will be excluded from this study if any of the following criteria are met:

          1. Patient has received previous systemic anticancer therapy.

             • Patients receiving adjuvant or neoadjuvant treatment and completed ≥6 months prior
             to randomization are eligible.

          2. Patient has mixed hepatocellular carcinoma - iCCA disease.

          3. History and/or current evidence of any of the following disorders:

               -  Non-tumor related alteration of calcium-phosphorus homeostasis that is clinically
                  significant in the opinion of the Investigator.

               -  Ectopic mineralization/calcification, including but not limited to soft tissue,
                  kidneys, intestine, or myocardia and lung, considered clinically significant in
                  the opinion of the Investigator.

               -  Retinal disorder confirmed by retinal examination and considered clinically
                  significant in the opinion of the ophthalmologist.

          4. History or current evidence of uncontrolled ventricular arrhythmias

          5. Fridericia's corrected QT interval (QTcF) > 470 ms on electrocardiogram (ECG)
             conducted during Screening.

          6. Treatment with any of the following within the specified time frame prior to the first
             dose of study therapy, or failure to recover from side effects of these prior
             therapies:

               -  Major surgery within the previous 4 weeks (the surgical incision should be fully
                  healed prior to the first dose of study therapy).

               -  Radiotherapy (any dose) for extended field within 4 weeks or limited field
                  radiotherapy within 2 weeks, and/or has not recovered from acute impact of
                  radiotherapy.

               -  Patients with locoregional therapy, e.g. transarterial chemoembolization (TACE),
                  selective internal radiotherapy (SIRT) or ablation within 4 weeks.

               -  Any history of liver transplant.

          7. A serious illness or medical condition(s) including, but not limited to, the
             following:

               -  Brain metastases that are untreated or clinically or radiologically unstable
                  (that is, have been stable for <1 month).

               -  Known acute systemic infection.

               -  Myocardial infarction, severe/unstable angina, or symptomatic congestive heart
                  failure within the previous 6 months.

               -  Chronic nausea, vomiting, or diarrhea considered to be clinically significant in
                  the opinion of the Investigator.

               -  Congenital long QT syndrome, or any known history of torsade de pointes, or
                  family history of unexplained sudden death.

               -  Other severe acute or chronic medical or psychiatric condition or laboratory
                  abnormality that in the judgment of the Investigator would make the patient
                  inappropriate for entry into this study.

          8. Patients with a history of another primary malignancy that is currently clinically
             significant, and has potential for metastases or currently requires active
             intervention.

          9. Pregnant or breast-feeding female.

         10. The patient is unable to take oral medication.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Measurements of disease will be performed using RECIST guidelines. Tumor assessments CT or MRI will be performed at baseline and at the end of every 2 cycles up to Cycle 4 and every 3 cycles beyond cycle 4 (or as clinically indicated).
Time Frame:10 months
Safety Issue:
Description:Response assessments will be made based on RECIST guidelines (version 1.1, 2009) for solid tumors

Secondary Outcome Measures

Measure:ORR
Time Frame:10 months
Safety Issue:
Description:defined as the proportion of patients experiencing a best overall response of partial response (PR) or complete response (CR) (per RECIST 1.1), based on ICR.
Measure:DCR
Time Frame:10 months
Safety Issue:
Description:defined as the proportion of patients experiencing a best overall response of partial response (PR) or complete response (CR) (per RECIST 1.1), based on ICR.
Measure:PFS per Investigator assessment
Time Frame:10 months
Safety Issue:
Description:defined as the time from date of randomization to the date of disease progression based on Investigator assessment of radiographic images or death, whichever occurs first.
Measure:DOR
Time Frame:10 months
Safety Issue:
Description:defined as the time from the first documentation of response (per RECIST 1.1 and based on central assessment of radiologic images) to the first documentation of objective tumor progression or death due to any cause, whichever occurs first.
Measure:PFS2
Time Frame:10 months
Safety Issue:
Description:defined as the time from randomization to subsequent disease progression per Investigator assessment after initiation of next-line therapy or death from any cause (whichever occurs first).

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Taiho Oncology, Inc.

Trial Keywords

  • Futibatinib
  • Advanced Cholangiocarcinoma
  • FGFR2
  • Fusion
  • Rearrangement
  • TAS-120

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