Clinical trial NCT04149691: Safety, Tolerability and Pharmacokinetics of Oral CPL304110, in Adult Subjects With Advanced Solid Malignancies
Official title: A Phase I, Open-label, Multicentre, Dose Escalation Study to Assess Safety, Tolerability and Pharmacokinetics of Oral CPL304110, in Adult Subjects With Advanced Solid Malignancies
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Gastric Cancer
Bladder Cancer
Squamous Non-small Cell Lung Cancer
Cholangiocarcinoma
Sarcoma
Endometrial Cancer
Other Solid Tumours
Keywords: FGFR
kinase inhibitor
advanced solid tumors
carcinoma
neoplasms
gastric cancer
bladder cancer
squamous non-small cell lung cancer
squamous immunophenotype
Lead sponsor: Celon Pharma SA
Sponsor class: INDUSTRY
Collaborators: name: National Center for Research and Development, Poland
First posted: 2019-11-04
Enrollment: 42
Sex: ALL
Minimum age (years): 25
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to determine to evaluate safety and tolerability of CPL304110 when administered once daily to adults with advanced solid malignancies.

Detailed description: 01FGFR2018 is an Open-label, Multicentre, Dose Escalation Study to Assess Safety, Tolerability and Pharmacokinetics of Oral CPL304110, in Adult Subjects with Advanced Solid Malignancies. The study consists of 3 parts: initial dose escalation (Part 1 - without FGFR, fibroblast growth factor receptor, molecular aberrations), dose escalation (Part 2 - with FGFR molecular aberrations) and dose extension (Part 3 - with FGFR molecular aberrations).

Eligibility criteria: Inclusion Criteria:

* Patient or legal guardian, if permitted by local regulatory authorities, provides informed consent to participate in the study must be performed before any procedure's protocol related
* age of ≥25 years old
* Performance Score ≥70 in accordance with the Karnofsky Performance Score (KPS),
* life expectancy period of at least 3 months on the screening day,
* Have measurable disease according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
* subject (or his/her partner) of childbearing potential willingness to use acceptable forms of contraception
* adequate blood, liver, renal and urine parameters
* phosphate levels within normal range
* HIV, HCV (hepatitis C virus) and HBV negative (hepatitis B virus),
* adequate cardiac function

Inclusion Criteria Specific for parts:

Part 1

* Patients with histologically confirmed advanced gastric cancer, bladder cancer, squamous lung cancer or non-small cell lung cancer with squamous immunophenotype, cholangiocarcinoma, sarcoma or endometrial cancer, be refractory to prior therapies and without effective further treatment options.

Part 2 and 3

* Patients with histologically confirmed advanced gastric cancer, bladder cancer, squamous lung cancer or non-small cell lung cancer with squamous immunophenotype, be refractory to prior therapies and without effective further treatment options.
* Subject's archival formalin-fixed paraffin-embedded (FFPE) tumour sample available for molecular alteration diagnostics, and/or a possibility to collect a new biopsy.
* Present molecular alteration within FGFR 1, 2 or 3

Exclusion Criteria:

* Any other current malignancy or malignancy diagnosed within the past five (5) years.
* Active brain metastases or leptomeningeal metastases.
* concurrent anticancer treatment within 28 days before the start of trial treatment; major surgery within 28 days before the start of trial treatment); use of blood transfusion within 7 days before the start of trial treatment,
* prior therapy with an agent directed to another FGFR inhibitor,
* pregnancy and/or breastfeeding,
* phosphate levels above the upper limit of normal,
* ectopic calcification/mineralization,
* endocrine alteration related to calcium/phosphate homeostasis e.g. parathyroid disorders, history of parathyroidectomy,
* concomitant therapies increasing calcium/phosphate serum levels,
* inability to take oral medicines,
* corneal disorder and/or keratopathy,
* persisting toxicity related to prior therapy Grade \> 1 CTCAE v5.0, except polyneuropathy and alopecia,
* clinically significant (i.e., active) cardiovascular disease. History of abdominal fistula, bowel obstruction (Grade IV), gastrointestinal perforation, intra-abdominal abscess within 6 months of enrollment. Other significant diseases, which, in the opinion of the investigator, might impair the subject's tolerance of trial treatment.
* Receipt of any organ transplantation including allogeneic stem-cell transplantation.

Exclusion Criteria Specific for parts:

Part 2 and 3

* No FFPE tumour sample available to conduct FGFR alteration eligibility tests and no biopsy option.

Primary outcomes:
measure: Maximum tolerated dose (MTD)
timeFrame: First cycle of 28 days
measure: Safety profile
timeFrame: First cycle of 28 days
Secondary outcomes:
measure: Recommended Phase 2 Dose (RP2D) determined on the base of the MTD.
timeFrame: Approximately up to 12 months
measure: ORR, objective rate response
timeFrame: Approximately up to 12 months
measure: Maximum plasma concentration (Cmax)
timeFrame: up to 24 hours after CPL304110 administration
measure: Time to maximum plasma concentration (tmax)
timeFrame: up to 24 hours after CPL304110 administration
measure: Area under the plasma concentration versus time curve (AUC) from 0 up to the time of last quantifiable concentration (AUC0-t)
timeFrame: up to the time of last quantifiable concentration after CPL304110 administration
measure: Area under the plasma concentration versus time curve AUC from 0 to infinity (AUC0-inf)
timeFrame: up to 24 hours after CPL304110 administration
measure: Terminal half-life (t½)
timeFrame: up to 24 hours after CPL304110 administration
measure: Kel: Terminal elimination rate constant
timeFrame: up to 24 hours after CPL304110 administration
Other outcomes:
Locations:
city: Gdańsk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne w Gdańsku
city: Nadarzyn
country: Poland
facility: BioResearch Group sp. z o.o.
city: Olsztyn
country: Poland
facility: SP ZOZ MSWiA z Warmińsko-Mazurskim Centrum Onkologii w Olsztynie
city: Otwock
country: Poland
facility: Klinika Onkologii, Europejskie Centrum Zdrowia
city: Warsaw
country: Poland
facility: Centrum Onkologii - Instytut im. Marii Skłodowskiej-Curie
city: Warsaw
country: Poland
facility: Instytut Gruźlicy i Chorób Płuc
city: Warsaw
country: Poland
facility: Wojskowy Instytut Medyczny
Study officials:
References:
citation: Yamani A, Zdzalik-Bielecka D, Lipner J, Stanczak A, Piorkowska N, Stanczak PS, Olejkowska P, Hucz-Kalitowska J, Magdycz M, Dzwonek K, Dubiel K, Lamparska-Przybysz M, Popiel D, Pieczykolan J, Wieczorek M. Discovery and optimization of novel pyrazole-benzimidazole CPL304110, as a potent and selective inhibitor of fibroblast growth factor receptors FGFR (1-3). Eur J Med Chem. 2021 Jan 15;210:112990. doi: 10.1016/j.ejmech.2020.112990. Epub 2020 Nov 7.