An open-label, randomized, actively controlled, multicenter phase III study to evaluate the efficacy and safety of Pemigatinib versus Gemcitabine plus chemotherapy with Cisplatin as first-line treatment in patients with unresectable or metastatic cholangiocarcinoma with FGFR2 rearrangement (FIGHT-302)
Résumé de l'étude
In the planned study, the efficacy and safety of Pemigatinib as first-line therapy in participants with inoperable and/or metastatic bile duct cancer will be investigated. Current practice guidelines for this population suggest that Gemcitabine plus Cisplatin is the preferred first-line treatment. The proposed study design is a randomized and actively controlled study of Pemigatinib versus Gemcitabine plus Cisplatin. Classification factors for region and disease stage will be used to ensure appropriate distribution of similar populations across treatment groups. The region was chosen due to differences in diagnosis and initial treatment; tumor burden (locally advanced vs. distant metastasis) is the second classification factor. Advanced disease (locally or metastatic) may contribute to a more complicated disease status. The study will be open due to the clear pharmacodynamic effect of the study drug on the participant (increase in serum phosphate/hyperphosphatemia). Even with a double-dummy design, it is difficult to effectively blind the study, as the serum phosphate increase occurs in most participants treated with Pemigatinib. An independent central reviewer will be engaged to assess tumor response to support the primary and secondary endpoints and thus minimize bias. Participants must have a documented gene rearrangement (FGFR2 translocation) from the sponsor's central laboratory to confirm eligibility. Approximately 432 participants will be randomized in a 1:1 ratio into 2 treatment groups, stratified by geographic region (Western regions [North America and EU] vs. Asia-Pacific region vs. rest of the world) and by tumor burden (locally advanced vs. distant metastases)
(BASEC)
Intervention étudiée
• Treatment Group A: Pemigatinib (13.5 mg once daily) with continuous administration (one cycle consists of 3 weeks)
• Treatment Group B: Gemcitabine (1,000 mg/m2) plus Cisplatin (25 mg/m2) as intravenous infusion on days 1 and 8 of each 3-week cycle for up to 8 cycles
(BASEC)
Maladie en cours d'investigation
unresectable or metastatic cholangiocarcinoma (bile duct cancer)
(BASEC)
• Ability to understand a written patient information and informed consent form for the study and willingness to sign them. • Men and women who are at least 18 years old at the time of signing the patient information and informed consent form. • A previously untreated, histologically confirmed, inoperable and/or metastatic bile duct cancer (stage IV). • A measurable disease by X-ray or assessable by computed tomography (CT) or magnetic resonance imaging (MRI). (BASEC)
Critères d'exclusion
• Prior systemic cancer therapy due to unresectable and/or metastatic disease. • Concurrent cancer therapy except for the therapies being tested in this study. • The participant must not be suitable for a potential curative surgery. • Current evidence of clinically significant corneal or retinal disease, confirmed by ophthalmological examination. (BASEC)
Lieu de l’étude
Berne, Zurich
(BASEC)
Sponsor
Incyte Corporation, US IQVIA AG, Branch Basel
(BASEC)
Contact pour plus d'informations sur l'étude
Personne de contact en Suisse
Dr. Joachim Mertens
+41 44 255 91 67
joachim.mertens@clutterusz.chUniversitaetsspital Zuerich
(BASEC)
Informations générales
Incyte Corporation
(ICTRP)
Informations scientifiques
Incyte Corporation
(ICTRP)
Nom du comité d'éthique approbateur (pour les études multicentriques, uniquement le comité principal)
Commission cantonale de Zurich
(BASEC)
Date d'approbation du comité d'éthique
13.11.2019
(BASEC)
Identifiant de l'essai ICTRP
NCT03656536 (ICTRP)
Titre officiel (approuvé par le comité d'éthique)
A Phase 3, Open-Label, Randomized, Active-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Pemigatinib Versus Gemcitabine Plus Cisplatin Chemotherapy in First-Line Treatment of Participants With Unresectable or Metastatic Cholangiocarcinoma With FGFR2 Rearrangement (FIGHT-302) (BASEC)
Titre académique
A Phase 3, Open-Label, Randomized, Active-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Pemigatinib Versus Gemcitabine Plus Cisplatin Chemotherapy in First-Line Treatment of Participants With Unresectable or Metastatic Cholangiocarcinoma With FGFR2 Rearrangement (FIGHT-302) (ICTRP)
Titre public
A Study to Evaluate the Efficacy and Safety of Pemigatinib Versus Chemotherapy in Unresectable or Metastatic Cholangiocarcinoma (ICTRP)
Maladie en cours d'investigation
Unresectable CholangiocarcinomaMetastatic Cholangiocarcinoma (ICTRP)
Intervention étudiée
Drug: PemigatinibDrug: GemcitabineDrug: Cisplatin (ICTRP)
Type d'essai
Interventional (ICTRP)
Plan de l'étude
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label). (ICTRP)
Critères d'inclusion/exclusion
Inclusion Criteria:
- Male and female participants at least 18 years of age at the time of signing the
informed consent form (ICF).
- Histologically or cytologically confirmed cholangiocarcinoma that is previously
untreated and considered unresectable and/or metastatic (Stage IV per the American
Joint Committee on Cancer (AJCC) Cancer Staging Manual).
- Radiographically measurable or evaluable disease by CT or MRI per RECIST v1.1
criteria.
- Eastern Cooperative Oncology Group performance status 0 to 1.
- Documented FGFR2 rearrangement.
- Willingness to avoid pregnancy or fathering children.
Exclusion Criteria:
- Received prior anticancer systemic therapy for unresectable and/or metastatic
disease (not including adjuvant/neo-adjuvant treatment completed at least 6 months
prior to enrollment, and participants that have received treatment for locally
advanced disease with trans-arterial chemoembolization or selective internal
radiation therapy, if clear evidence of radiological progression is observed before
enrollment, or enrolled as of Amendment 6 (or Amendment 5-JP2) and the participant
received 1 cycle of gemcitabine plus cisplatin [the start of study drug {Cycle 1 Day
1} must be at least 14 days and = 4 weeks {28 days} from the last dose of
gemcitabine plus cisplatin]).
- Child-Pugh B and C.
- Toxicities related to prior therapy(ies) must be Common Terminology Criteria for
Adverse Events (CTCAE) v5.0 = Grade 1 at the time of screening.
- Concurrent anticancer therapy, other than the therapies being tested in this study.
- Participant is a candidate for potentially curative surgery.
- Current evidence of clinically significant corneal (including but not limited to
bullous/band keratopathy, corneal abrasion, inflammation/ulceration, and
keratoconjunctivitis) or retinal disorder (including but not limited to central
serous retinopathy, macular/retinal degeneration, diabetic retinopathy, retinal
detachment) as confirmed by ophthalmologic examination.
- Radiation therapy administered within 4 weeks of enrollment/randomization/first dose
of study treatment.
- Known central nervous system (CNS) metastases or history of uncontrolled seizures.
- Known additional malignancy that is progressing or requires active treatment
(exceptions: basal cell carcinoma of the skin, squamous cell carcinoma of the skin,
or in situ cervical cancer that has undergone potentially curative therapy).
- Laboratory values at screening outside the protocol-defined range.
- History of calcium and phosphate hemostasis disorder or systemic mineral imbalance
with ectopic calcification of soft tissues (exception: commonly observed
calcifications in soft tissues, such as the skin, kidney, tendons or vessels due to
injury, disease, and aging, in the absence of systemic mineral imbalance).
- Significant gastrointestinal disorders that could interfere with absorption,
metabolism, or excretion of pemigatinib.
- Clinically significant or uncontrolled cardiac disease.
- History or presence of an abnormal ECG, which, in the investigator's opinion, is
clinically meaningful.
- Chronic or current active infectious disease requiring systemic antibiotics or
antifungal or antiviral treatment within 2 weeks prior to enrollment (participants
with asymptomatic chronic infections on prophylactic treatment are allowed). Note:
HIV-positive participants are allowed if all of the following criteria are met: CD4+
count = 300/L, undetectable viral load, receiving antiretroviral therapy that does
not interact with study drug, and no HIV/AIDS-associated opportunistic infection in
the last 12 months.
- Use of any potent CYP3A4 inhibitors or inducers or moderate CYP3A4 inducers within
14 days or 5 half-lives (whichever is longer) before the first dose of study
treatment. Note: Moderate CYP3A4 inhibitors are not prohibited
- Known hypersensitivity or severe reaction to pemigatinib, gemcitabine, cisplatin, or
their excipients.
- Inadequate recovery from toxicity and/or complications from a major surgery before
starting therapy. (ICTRP)
non disponible
Critères d'évaluation principaux et secondaires
Progression-free survival (ICTRP)
Overall response rate;Overall survival;Duration of response;Disease control rate;Number of treatment-emergent adverse events;Quality of Life impact as assessed by the EQ-5D-3L questionnaire;Quality of Life impact as assessed by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-30 questionnaire;Quality of Life impact as assessed by the EORTC QLQ-BIL21 questionnaire (ICTRP)
Date d'enregistrement
non disponible
Inclusion du premier participant
non disponible
Sponsors secondaires
non disponible
Contacts supplémentaires
Peter Langmuir, MD, Incyte Corporation (ICTRP)
ID secondaires
2024-513513-12-00, 2018-002894-23, INCB 54828-302 (ICTRP)
Résultats-Données individuelles des participants
non disponible
Informations complémentaires sur l'essai
https://clinicaltrials.gov/study/NCT03656536 (ICTRP)
Résultats de l'essai
Résumé des résultats
non disponible
Lien vers les résultats dans le registre primaire
non disponible