Pemigatinib After Curative Local Therapy in Advanced iCCA With FGFR2 Fusion/Rearrangements

NCT05565794 | Terminated Phase 2

• 3 other identifiers: PEARLDIFER2021-006232-50IKF-t055
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 10

Brief Summary

The aim of this phase II study is to determine whether pemigatinib is clinically efficious after curative local therapy such as surgery/ SBRT or ablation in iCCA patients harboring FGFR2 fusion/rearrangement and to assess the safety profile to support the continuation of the concept in a large, randomized trial for further development.

Conditions

Intrahepatic Cholangiocarcinoma; FGFR2 Gene Mutation; FGFR2 Gene Rearrangement; FGFR2 Gene Translocation

Keywords

intrahepatic cholangiocarcinoma; iCCA; FGFR2 fusion; FGRF2 rearrangement; FGFR2 alteration; FGFR2 mutation

Outcome Measures

Primary Outcomes (1)

• Objective response rate at time of progression

  Objective response rate according to investigator-based RECIST 1.1 assessment, defined as the proportion of allocated subjects with best response of complete or partial response within 12 months after the date of first administration of study treatment. Patients who receive anti-cancer treatment other than the study medication for any reason before reaching a complete or partial response will be identified as nonresponders in the assessment of ORR.

  through study completion, approx. 3 years

Secondary Outcomes (3)

• Overall survival

  up to 3 years

• Quality of Life asssed by EORTC-QLQ-C30 with additional appendix BIL21

  from screening until end of study, approx. 3 years

• Incidence of treatment-related adverse events

  from screening until end of study, approx. 3 years

Study Arms (1)

Pemigatinib

EXPERIMENTAL

Intake of 13.5 mg pemigatinib once daily per oral

Drug: Pemigatinib

Interventions

Pemigatinib DRUG

Intake of up to 3 tablets of pemigatinib (4,5 mg each) daily per oral for 14 days in a 21-day cycle (maximum of 18 cycles in total)

Also known as: Pemazyre

Pemigatinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients who meet all of the following criteria are eligible for trial participation:
• Signed informed consent form (ICF).
• Patients\*, age ≥ 18 years at the time of signing the informed consent form.
• Histologically proven and curatively treatable localized intrahepatic biliary tract cancer (iCCA only) with a previous maximum of 5 cm in diameter, without signs of metastatic disease, and proven FGRF2- fusions/ rearrangements, identified by routine FISH or by NGS testing.
• Note: Only CE-IVD marked NGS-tests are applicable which cover FGFR2 fusions and rearrangements
• Patients previously received SBRT or another minimally invasive technique (e.g., laparoscopic liver resection) up to 12 weeks prior to enrolment
• Female patients who are considered as woman of childbearing potential (WOCBP) as well as male patients who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year during the treatment as well as up to 1 week after the last dose of pemigatinib. Female patients who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile, see section 13.5) as well as azoospermic male patients do not require contraception. Female patients considered as WOCBP must have a negative pregnancy test within the last 7 days prior to the start of study therapy.
• ECOG performance status 0-1.
• Appropriate hematological, hepatic and renal function:
• Absolute number of neutrophils ≥ 1.5 x 109/L
• Platelets ≥ 100 x 109/L
• Hemoglobin ≥ 9 g/dL (5.58 mmol/L)
• Total bilirubin ≤ 1.5 times the upper limit of normal (ULN)
• AST (SGOT) and ALT (SGPT) ≤ 2.5 x ULN without existing liver metastases, or ≤ 5 x ULN in the presence of liver metastases; AP ≤ 5 x ULN.
• Serum creatinine ≤ 1.5 x ULN or creatinine clearance (measured by 24h urine) ≥ 40 mL/min (i.e., if the serum creatinine level is \> 1.5 x ULN, then a 24-h urine test must be performed to check the creatinine clearance to be determined).

You may not qualify if:

• Patients who meet at least one of the following criteria are not eligible for trial participation:
• Presence of tumors other than biliary tract cancer or a secondary tumor other than squamous or basal cell carcinomas of the skin or in situ carcinomas of the cervix which have been effectively treated. The Sponsor decides to include patients who have received curative treatment and have been disease-free for at least 3 years.
• Metastatic biliary tract cancer (intrahepatic, hilar, or distal CCA as well as gallbladder carcinoma) disease.
• Pretreatment with any systemic anti-cancer therapy.
• Simultaneous, ongoing systemic immunotherapy, chemotherapy, or hormone therapy not described in the study protocol.
• Simultaneous treatment with a different anti-cancer therapy other than that provided in the study (excluding palliative radiotherapy only for symptom control).
• Previous therapy with an FGFR- inhibitor.
• Stage B cirrhosis according to Child-Pugh criteria (or worse) or cirrhosis (of any grade) with a history of hepatic encephalopathy or clinically significant ascites resulting from cirrhosis. Clinically significant ascites is defined as ascites resulting from cirrhosis requiring diuretics or paracentesis.
• Known allergic / hypersensitive reactions to at least one of the treatment components.
• Other serious illnesses or medical ailments within the last 12 months prior to the start of the study.
• 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.
• 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).
• History of hypovitaminosis D requiring supraphysiologic doses (eg, 50,000 UI/weekly) to replenish the deficiency. NOTE: Participants receiving vitamin D supplements are eligible .
• 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 (refer to section Fehler! Verweisquelle konnte nicht gefunden werden. Appendix 3 for a list of CYP3A4 inhibitors and inducers).
• Presence of an active, uncontrollable infection.

Sponsors & Collaborators

• Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest: lead
• Incyte Biosciences International Sàrl: collaborator

Study Sites (10)

Universitätsklinikum Augsburg III. Medizinische Klinik

Augsburg, 86156, Germany

Location

Charité - Universitätsmedizin Berlin

Berlin, 13353, Germany

Location

Universitätsklinikum Köln AöR Klinik für Gastroenterologie und Hepatologie

Cologne, 50937, Germany

Location

Medizinische Klinik und Poliklinik I Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden

Dresden, 01307, Germany

Location

Universitätsklinikum Düsseldorf Klinik für Gastroenterologie, Hepatologie und Infektiologie

Düsseldorf, 40225, Germany

Location

Klinikum Esslingen GmbH Klinik für Allgemeine Innere Medizin Onkologie / Hämatologie, Gastroenterologie und Infektiologie

Esslingen am Neckar, 73730, Germany

Location

Klinikum Esslingen

Esslingen am Neckar, 73730, Germany

Location

Krankenhaus Nordwest

Frankfurt, 60488, Germany

Location

Universitätsklinikum Jena Klinik für Innere Medizin II

Jena, 07747, Germany

Location

TUM Universitätsklinikum Klinikum rechts der Isar Technische Universität München Klinik für Poliklinik und für Innere Medizin

München, 81675, Germany

Location

MeSH Terms

Conditions

Cholangiocarcinoma

Interventions

pemigatinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Study Officials

• Thorsten Goetze, Prof. Dr.

  Krankenhaus Nordwest, Frankfurt

  PRINCIPAL INVESTIGATOR

• Salah-Eddin Al-Batran, Prof. Dr.

  Institut für Klinische Krebsforschung IKF GmbH

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 28, 2022
• First Posted: October 4, 2022
• Study Start: November 11, 2022
• Primary Completion: March 27, 2025
• Study Completion: March 27, 2025
• Last Updated: April 13, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

DE (10)