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

NCT04149691 | Recruiting Phase 1

• 1 other identifier: 01FGFR2018
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 7

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.

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

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose (MTD)

  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.

  First cycle of 28 days

• Safety profile

  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.

  First cycle of 28 days

Secondary Outcomes (8)

• Recommended Phase 2 Dose (RP2D) determined on the base of the MTD.

  Approximately up to 12 months

• ORR, objective rate response

  Approximately up to 12 months

• Maximum plasma concentration (Cmax)

  up to 24 hours after CPL304110 administration

• Time to maximum plasma concentration (tmax)

  up to 24 hours after CPL304110 administration

• 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

Study Arms (1)

CPL304110

EXPERIMENTAL

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

Drug: CPL304110

Interventions

CPL304110 DRUG

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

Also known as: PG19

CPL304110

Eligibility Criteria

• Age: 25 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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.
• Part 2 and 3

Sponsors & Collaborators

• Celon Pharma SA: lead
• National Center for Research and Development, Poland: collaborator

Study Sites (7)

Uniwersyteckie Centrum Kliniczne w Gdańsku

Gdansk, Poland

RECRUITING

BioResearch Group sp. z o.o.

Nadarzyn, Poland

RECRUITING

SP ZOZ MSWiA z Warmińsko-Mazurskim Centrum Onkologii w Olsztynie

Olsztyn, Poland

RECRUITING

Klinika Onkologii, Europejskie Centrum Zdrowia

Otwock, Poland

NOT YET RECRUITING

Centrum Onkologii - Instytut im. Marii Skłodowskiej-Curie

Warsaw, Poland

RECRUITING

Instytut Gruźlicy i Chorób Płuc

Warsaw, Poland

RECRUITING

Wojskowy Instytut Medyczny

Warsaw, Poland

NOT YET RECRUITING

Related Publications (1)

• 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.

  PMID: 33199155 DERIVED

MeSH Terms

Conditions

Stomach Neoplasms; Urinary Bladder Neoplasms; Cholangiocarcinoma; Sarcoma; Endometrial Neoplasms; Carcinoma; Neoplasms

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Connective and Soft Tissue; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Diseases; Genital Diseases, Female; Genital Diseases

Central Study Contacts

CROS CRO

CONTACT

+48 791 690 990; clinicaltrials@cros-cro.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 31, 2019
• First Posted: November 4, 2019
• Study Start: July 19, 2019
• Primary Completion: June 1, 2024
• Study Completion: June 1, 2024
• Last Updated: February 7, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

PL (7)