Safety, Tolerability and Pharmacokinetics of Oral CPL304110, in Adult Subjects With Advanced Solid Malignancies

Sponsor

Celon Pharma SA (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04149691

Collaborator

National Center for Research and Development, Poland (Other)

Enrollment

Locations

Arm

40.4

Anticipated Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Gastric Cancer Bladder Cancer Squamous Non-small Cell Lung Cancer Cholangiocarcinoma Sarcoma Endometrial Cancer Other Solid Tumours	Drug: CPL304110	Phase 1

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).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

42 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jul 19, 2019

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

Dec 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CPL304110 CPL304110 will be administered once daily to adults with advanced solid malignancies in 28-day cycles.	Drug: CPL304110 CPL304110 is to be administered orally as hard gelatine capsules once daily in 28-day cycles. Other Names: PG19

Arm

Intervention/Treatment

Experimental: CPL304110

CPL304110 will be administered once daily to adults with advanced solid malignancies in 28-day cycles.

Drug: CPL304110

CPL304110 is to be administered orally as hard gelatine capsules once daily in 28-day cycles.

Other Names:

PG19

Outcome Measures

Primary Outcome Measures

Maximum tolerated dose (MTD) [First cycle of 28 days]
Maximum tolerated dose (MTD) of CPL304110 when administered orally once daily to adults with advanced solid malignancies. The MTD is the highest dose associated with the occurrence of dose-limiting toxicities (DLTs) in <33% of patients.
Safety profile [First cycle of 28 days]
Overall safety profile of CPL304110, as assessed by the type, frequency, severity, timing, and relationship to study drug of any adverse events (AEs), serious adverse events (SAEs), and changes in vital signs, ECGs, and safety laboratory test.

Secondary Outcome Measures

Recommended Phase 2 Dose (RP2D) determined on the base of the MTD. [Approximately up to 12 months]
The RP2D will be determined after review and discussion of the pharmacokinetics (PK) profile, type and severity of drug related toxicity and clinical suitability for long-term administration.
ORR, objective rate response [Approximately up to 12 months]
ORR, objective rate response defined as the rate of confirmed complete response (CR) or partial response (PR) by RECIST 1.1.
Maximum plasma concentration (Cmax) [up to 24 hours after CPL304110 administration]
Cmax defines the maximum concentration of the product in plasma during observation period.
Time to maximum plasma concentration (tmax) [up to 24 hours after CPL304110 administration]
tmax defines Time to reach maximum plasma concentration
Area under the plasma concentration versus time curve (AUC) from 0 up to the time of last quantifiable concentration (AUC0-t) [up to the time of last quantifiable concentration after CPL304110 administration]
AUC(0-t) defines the area under the curve of plasma concentration vs time, from time point zero up to the time of last quantifiable concentration
Area under the plasma concentration versus time curve AUC from 0 to infinity (AUC0-inf) [up to 24 hours after CPL304110 administration]
AUC0-inf defines the area under the curve of plasma concentration vs time, from time point zero extrapolated to infinity
Terminal half-life (t½) [up to 24 hours after CPL304110 administration]
Plasma elimination half-life
Kel: Terminal elimination rate constant [up to 24 hours after CPL304110 administration]
Terminal elimination rate constant

Eligibility Criteria

Criteria

Ages Eligible for Study:

25 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	Country
1	Uniwersyteckie Centrum Kliniczne w Gdańsku	Gdańsk	Poland
2	BioResearch Group sp. z o.o.	Nadarzyn	Poland
3	SP ZOZ MSWiA z Warmińsko-Mazurskim Centrum Onkologii w Olsztynie	Olsztyn	Poland
4	Klinika Onkologii, Europejskie Centrum Zdrowia	Otwock	Poland
5	Centrum Onkologii - Instytut im. Marii Skłodowskiej-Curie	Warsaw	Poland
6	Instytut Gruźlicy i Chorób Płuc	Warsaw	Poland
7	Wojskowy Instytut Medyczny	Warsaw	Poland