Primary end point• Progression-free survival (PFS) per ICR central assessmentSecondary end point• Objective response rate (ORR)• Disease control rate (DCR)• Overall survival (OS)• PFS according to Investigator assessment of radiologic images•…
ID
Source
Brief title
Condition
- Miscellaneous and site unspecified neoplasms benign
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
PFS per central assessment (primary): defined as the time from date of
randomization to the date of documentation of disease progression by ICR, or
date of death, whichever occurs first.
Secondary outcome
• ORR: 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.
• DCR: defined as the proportion of patients experiencing a best overall
response of stable disease (SD), PR, or CR (per RECIST 1.1), based on
central assessment of radiologic images.
• OS: measured from the date of randomization until the date of death due to
any cause.
• PFS per Investigator assessment: 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.
Background summary
Aberrations in fibroblast growth factor (FGF) or the FGF receptor (FGFR) are a
reported genetic modification in cholangiocarcinoma (CCA); in particular, FGFR2
gene rearrangements, including gene fusions, have been identified as an early
driver of oncogenic events in approximately 15% of CCA patients. Futibatinib
(TAS-120), an oral, highly selective, irreversible tyrosine kinase inhibitor
(TKI) that inhibits both mutant and wild-type FGFR1-4 isoforms, has shown
promising antitumor activity in preclinical studies against a variety of tumor
cell lines or tumor models harboring FGFR aberrations. In an ongoing Phase 1/2
clinical study (Study TAS-120-101), treatment with futibatinib resulted in
further evidence of efficacy.
The Phase 3 study described in this protocol will evaluate the efficacy and
safety of futibatinib against that of the current standard of care
(gemcitabine-cisplatin chemotherapy) in the first-line treatment of patients
with locally advanced, metastatic, or recurrent unresectable intrahepatic CCA
(iCCA) harboring FGFR2 gene rearrangements.
Study objective
Primary end point
• Progression-free survival (PFS) per ICR central assessment
Secondary end point
• Objective response rate (ORR)
• Disease control rate (DCR)
• Overall survival (OS)
• PFS according to Investigator assessment of radiologic images
• Treatment-emergent adverse events (TEAEs), including serious adverse events
(SAE's), clinical laboratory tests, vital signs, ophthalmological exams and
12-lead electrocardiogram (ECG)
Exploratory
• PFS on next-line therapy (PFS2)
• Duration of response (DOR)
• Patient-reported outcomes (PRO)
• To assess the population pharmacokinetics (Pop PK) of futibatinib and to
explore the relationship
between PK and efficacy or toxicity.
Study design
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:
o 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
o 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.
Intervention
• 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:
o 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
o 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.
Study burden and risks
TAS-120-301 study and the procedures are designed to ensure the safety of
participants. Patients with iCCA who harbor FGFR2 rearrangement as confirmed by
central lab will be randomized at 1:1 ratio to either experimental arm or
control arm. Additionally, an assessment was made of the immediate necessity of
patients eligible for recruitment into studies with futibatinib during the
Covid-19 pandemic. There is a marked evidence of absence of curative treatments
or viable alternative therapies for cancer patients overall. In particular,
patients with FGFR mutations have no approved targeted treatment available in
the EU and their condition is life-threatening and chronically debilitating.
For these reasons, the Sponsor believes that new studies with futibatinib can
be started during the Covid-19 pandemic as the benefits to patients largely
outweigh the risks associated with study procedures. The Sponsor has made plans
and allows minimise the risk of undue exposure to Taiho*s Trial patients
including drug shipment from Study Sites to patients, remote SDVs (where
feasible), protocol deviation tracking. The Sponsor performs a risk assessment
of the study on an ongoing basis and prioritizes patient*s safety.
Given the information above, the Sponsor concludes that the overall
benefit/risk supports the initiation of TAS-120-301 study. Taiho Oncology Inc.,
procedures are designed to primarily ensure the safety of participants,
especially during the COVID-19 pandemic.
101 Carnegie Center Suite 101
Princeton NJ 08540
US
101 Carnegie Center Suite 101
Princeton NJ 08540
US
Listed location countries
Age
Inclusion criteria
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.
Exclusion criteria
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.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2019-004630-42-NL |
| ClinicalTrials.gov | NCT04093362 |
| CCMO | NL73877.091.20 |