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

February 6, 2024 updated by: Celon Pharma SA

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

42

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Poland
      • Gdańsk, Poland
        • Recruiting
        • Uniwersyteckie Centrum Kliniczne w Gdańsku
      • Nadarzyn, Poland
        • Recruiting
        • BioResearch Group sp. z o.o.
      • Olsztyn, Poland
        • Recruiting
        • SP ZOZ MSWiA z Warmińsko-Mazurskim Centrum Onkologii w Olsztynie
      • Otwock, Poland
        • Not yet recruiting
        • Klinika Onkologii, Europejskie Centrum Zdrowia
      • Warsaw, Poland
        • Recruiting
        • Centrum Onkologii - Instytut im. Marii Skłodowskiej-Curie
      • Warsaw, Poland
        • Recruiting
        • Instytut Gruźlicy i Chorób Płuc
      • Warsaw, Poland
        • Not yet recruiting
        • Wojskowy Instytut Medyczny

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

25 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum tolerated dose (MTD)
Time Frame: 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.
First cycle of 28 days
Safety profile
Time Frame: 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.
First cycle of 28 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Recommended Phase 2 Dose (RP2D) determined on the base of the MTD.
Time Frame: 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.
Approximately up to 12 months
ORR, objective rate response
Time Frame: 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.
Approximately up to 12 months
Maximum plasma concentration (Cmax)
Time Frame: up to 24 hours after CPL304110 administration
Cmax defines the maximum concentration of the product in plasma during observation period.
up to 24 hours after CPL304110 administration
Time to maximum plasma concentration (tmax)
Time Frame: up to 24 hours after CPL304110 administration
tmax defines Time to reach maximum plasma concentration
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)
Time Frame: 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
up to the time of last quantifiable concentration after CPL304110 administration
Area under the plasma concentration versus time curve AUC from 0 to infinity (AUC0-inf)
Time Frame: 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
up to 24 hours after CPL304110 administration
Terminal half-life (t½)
Time Frame: up to 24 hours after CPL304110 administration
Plasma elimination half-life
up to 24 hours after CPL304110 administration
Kel: Terminal elimination rate constant
Time Frame: up to 24 hours after CPL304110 administration
Terminal elimination rate constant
up to 24 hours after CPL304110 administration

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Celon Pharma SA

Collaborators

National Center for Research and Development, Poland

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 19, 2019

Primary Completion (Estimated)

June 1, 2024

Study Completion (Estimated)

June 1, 2024

Study Registration Dates

First Submitted

October 31, 2019

First Submitted That Met QC Criteria

October 31, 2019

First Posted (Actual)

November 4, 2019

Study Record Updates

Last Update Posted (Actual)

February 7, 2024

Last Update Submitted That Met QC Criteria

February 6, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 01FGFR2018

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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