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
- Bile duct cancercholangiocarcinoma10027656
- Registration Number
- NL-OMON52381
- Lead Sponsor
- Taiho Oncology Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 3
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 3 months after the last dose.
9. Willing and able to comply with scheduled visits and study procedures.
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, eg, 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 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
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>PFS per central assessment (primary): defined as the time from date of<br /><br>randomization to the date of documentation of disease progression by ICR, or<br /><br>date of death, whichever occurs first.</p><br>
- Secondary Outcome Measures
Name Time Method <p>• ORR: defined as the proportion of patients experiencing a best overall<br /><br>response of partial response (PR) or complete response (CR) (per RECIST<br /><br>1.1), based on ICR.<br /><br>• DCR: defined as the proportion of patients experiencing a best overall<br /><br>response of stable disease (SD), PR, or CR (per RECIST 1.1), based on<br /><br>central assessment of radiologic images.<br /><br>• OS: measured from the date of randomization until the date of death due to<br /><br>any cause.<br /><br>• PFS per Investigator assessment: defined as the time from date of<br /><br>randomization to the date of disease progression based on Investigator<br /><br>assessment of radiographic images or death, whichever occurs first.</p><br>