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
- Conditions
- Advanced solid tumorsMedDRA version: 21.1Level: LLTClassification code 10065147Term: Malignant solid tumorSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-004630-42-PL
- Lead Sponsor
- Taiho Oncology, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 216
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:
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 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 cell (WBC) count = 2000/mm3 (= 2.0 × 109/L)
• Absolute neutrophil count (ANC) = 1000/mm3 (ie, = 1.0 × 109/L)
• Platelet count = 100,000/mm3 (= 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 study medication. 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 3 months after the last dose of study therapy, or according to the local label for each study therapy (whichever is longer).
9. Willing and able to comply with scheduled visits and study procedures.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 162
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 54
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 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, selective internal radiotherapy, 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 whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen in the opinion of the Investigator.
9. Pregnant or breast-feeding female
10. The patient is unable to take oral medication.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: Progression-free survival (PFS) by independent central review (ICR), based on Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1);Secondary Objective: • Objective response rate (ORR)<br>• Disease control rate (DCR)<br>• Overall survival (OS)<br>• PFS according to Investigator assessment of radiologic images<br>• Safety and tolerability<br>;Primary end point(s): Progression Free Survival (PFS) per ICR central assessment;Timepoint(s) of evaluation of this end point: At the end of every 2 cycles (± 7 days) up to Cycle 4. Thereafter, every<br>3 cycles (± 7 days), or as clinically indicated, until radiologic progressive disease (PD) or initiation of new anticancer therapy (whichever occurs first).
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Secondary endpoints:<br>• Objective response rate (ORR)<br>• Disease control rate (DCR)<br>• Overall survival (OS)<br>• PFS according to Investigator assessment of radiologic images<br>• Treatment-emergent adverse events (TEAEs), including serious<br>adverse events (SAEs), clinical laboratory tests, vital signs, ophthalmological exams, and 12-lead electrocardiogram (ECG).;Timepoint(s) of evaluation of this end point: Bullet point 1-4: At the end of every 2 cycles (± 7 days) up to Cycle 4. Thereafter, every 3 cycles (± 7 days), or as clinically indicated, until radiologic progressive disease (PD) or initiation of new anticancer therapy (whichever occurs first).<br><br>Bullet point 5: All throughout the study, from the time main informed consent is signed through 30 days after administration of the last dose of study therapy or until the start of new anticancer therapy, whichever is earlier.