Phase 3 Study of BGJ398 (Oral Infigratinib) in First Line Cholangiocarcinoma With FGFR2 Gene Fusions/Translocations

Phase 1

• Conditions: Cholangiocarcinoma; MedDRA version: 20.0Level: PTClassification code 10008593Term: CholangiocarcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2018-004004-19-DE
• Lead Sponsor: QED Therapeutics, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-06-18
• Last Update Posted: 23 May 2022

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 300

Inclusion Criteria

1. Have histologically or cytologically confirmed unresectable locally advanced or metastatic cholangiocarcinoma. Subjects with gallbladder cancer or ampulla of Vater carcinoma are not eligible.
2. Have written documentation of local laboratory or central laboratory determination of known or likely activating FGFR2 fusions/rearrangement from a simple collected before randomization refer to Section 10.3.1 for the definition of a know or likely activating FGFR 2 fusion / rearrangement. Note: All subjects enrolled based on local molecular test results must have sufficient tumor tissue for confirmation of FGFR2 fusion/rearrangement by the central laboratory, but this central confirmation is not required prior to enrollment in the study.
3. Have an archival tumor tissue sample available with sufficient tumor for central FGFR2 fusion/rearrangement molecular testing by the Central Laboratory. However, if an archival tumor tissue sample is not available or does not meet requirements for central testing, a newly obtained (before randomization) tumor biopsy may be submitted instead. If a prestudy written documentation of FGFR2 fusion/rearrangement in tumor tissue is available from the central laboratory, an additional tumor sample does not need to be submitted for central FGFR2 fusion/translocation molecular testing. Note: All enrolled subject must have determination of FGFR2 gene fusions/translocations by the central laboratory as confirmation of local laboratory testing, but this central confirmation is not required prior to enrollment in the study.
4. Have full recovery from the following permitted prior treatments (as applicable) such that the subject is reasonably expected to tolerate study treatment (gemcitabine/cisplatin or infigratinib) according to the investigator’s assessment:
a. A non-curative operation (ie., R2 resection [with macroscopic residual disease] or palliative bypass surgery only)
b. Curative surgery with evidence of unresectable disease relapse requiring systemic chemotherapy
c. Adjuvant radiotherapy (with or without radio-sensitizing low-dose chemotherapy) for localized disease provided there has been clear evidence of disease progression before inclusion in this study
d. Adjuvant or neoadjuvant chemotherapy, provided recurrence occurred >6 months after the date of the last dose of adjuvant or neoadjuvant therapy and before randomization
e. Gemcitabine-based chemotherapy (specified in Appendix 5 [Section 17.5]) for advanced/unresectable or metastatic cholangiocarcinoma (=1 cycle)
i. Recovery from acute toxicities to the extent that would allow initiation of cisplatin-gemcitabine (absolute neutrophil count (ANC) =1,000/mm3 (=1.0 × 109/L); platelets =100,000/mm3 (=100× 109/L)
ii. Baseline tumor assessment at least 7 days after the last dose of chemotherapy and before randomization
iii. The window between the last dose of chemotherapy and the start of randomized study treatment must be =14 days and =5 weeks
f. Photodynamic treatment provided there is clear evidence of disease progression at the local site or at a new metastatic site.
5. Are = 18 years of age of either gender.
6. Have an Eastern Cooperative Oncology Group (ECOG) performance status = 1.
7. Have a life expectancy > 3 months.
8. Are able to read and/or understand the details of the study and provide written evidence of informed consent as approved by Institutional Review Board (IRB)/Independent Ethics Committee (IEC).
9. Are able to swallow and retain oral m

Exclusion Criteria

1. Have received treatment with any systemic anti-cancer therapy for unresectable locally, advanced or metastatic cholangiocarcinoma with the following exceptions:
a. Prior neoadjuvant or adjuvant therapy is permitted if documented disease recurrence occurred = 6 months after the last date of neoadjuvant or adjuvant therapy
b. One cycle of gemcitabine-based chemotherapy (specified in Appendix 5 [Section 17.5]) for locally advanced or metastatic cholangiocarcinoma is permitted before randomization
2. Have history of a liver transplant.
3. Have previously or currently is receiving treatment with a mitogen-activated protein kinase MEK or selective FGFR inhibitor.
4. Have neurological symptoms related to underlying disease requiring increasing doses of corticosteroids. Note: Steroid use for management of central nervous system tumors is allowed but must be at a stable or decreasing dose of corticosteroids for at least 2 weeks preceding
randomization.
5. Have a history of another primary malignancy within 3 years except adequately treated in situ carcinoma of the cervix or non-melanoma carcinoma of the skin or any other curatively treated malignancy that is not expected to require treatment for recurrence during the course of the study.
6. Have any other medical condition that would, in the investigator’s judgment, prevent the subject’s participation in the clinical study due to safety concerns or compliance with clinical study procedures.
7. Have current evidence of corneal or retinal disorder/keratopathy
including, but not limited to, bullous/band keratopathy, inflammation or ulceration, keratoconjunctivitis, confirmed by ophthalmic examination. Subjects with asymptomatic ophthalmic conditions assessed by the investigator to pose minimal risk for study participation may be enrolled in the study.
8. Have a history and/or current evidence of extensive tissue calcification including, but not limited to, the soft tissue, kidneys, intestine, myocardium, vascular system and lung with the exception of calcified lymph nodes, minor pulmonary parenchymal calcifications, and asymptomatic coronary calcification.
9. Have impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral infigratinib (eg., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection).
10. Have current evidence of endocrine alterations of calcium/phosphate homeostasis, eg., parathyroid disorders, history of parathyroidectomy, tumor lysis, tumoral calcinosis etc.
11. Are currently receiving or are planning to receive during participation in this study, treatment with agents that are known moderate or strong inducers or inhibitors of CYP3A4 and medications
which increase serum phosphorus and/or calcium concentration. Subjects are not permitted to receive enzyme-inducing anti-epileptic drugs, including carbamazepine, phenytoin, phenobarbital, and
primidone.
12. Have consumed grapefruit, grapefruit juice, grapefruit hybrids, pomegranates, star fruits, pomelos, Seville oranges or products containing juice of these fruits within 7 days prior to first dose of study drug.
13. Have insufficient bone marrow function.
14. Have insufficient bone marrow function.
15. Have amylase or lipase >2.0 × ULN
16. Have elevated phosphorus or abnormal serum calcium, or phosphorus, or calcium-phosphorus product =55 mg2/dL2;
a. Inorganic phosphorus >1.1xULN
b. Total corrected serum calcium >11mg/dL or <8

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified