Clinical Trials /

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

NCT04149691

Description:

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.

Related Conditions:
  • Bladder Carcinoma
  • Cholangiocarcinoma
  • Endometrial Carcinoma
  • Gastric Carcinoma
  • Non-Small Cell Lung Carcinoma
  • Sarcoma
  • Squamous Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: 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

Clinical Trial IDs

  • ORG STUDY ID: 01FGFR2018
  • NCT ID: NCT04149691

Conditions

  • Gastric Cancer
  • Bladder Cancer
  • Squamous Non-small Cell Lung Cancer
  • Cholangiocarcinoma
  • Sarcoma
  • Endometrial Cancer

Interventions

DrugSynonymsArms
CPL304110PG19CPL304110

Purpose

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).
    

Trial Arms

NameTypeDescriptionInterventions
CPL304110ExperimentalCPL304110 will be administered once daily to adults with advanced solid malignancies in 28-day cycles.
  • CPL304110

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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:25 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

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

Secondary Outcome Measures

Measure:Recommended Phase 2 Dose (RP2D) determined on the base of the MTD.
Time Frame:Approximately up to 12 months
Safety Issue:
Description: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.
Measure:ORR, objective rate response
Time Frame:Approximately up to 12 months
Safety Issue:
Description:ORR, objective rate response defined as the rate of confirmed complete response (CR) or partial response (PR) by RECIST 1.1.
Measure:Maximum plasma concentration (Cmax)
Time Frame:up to 24 hours after CPL304110 administration
Safety Issue:
Description:Cmax defines the maximum concentration of the product in plasma during observation period.
Measure:Time to maximum plasma concentration (tmax)
Time Frame:up to 24 hours after CPL304110 administration
Safety Issue:
Description:tmax defines Time to reach maximum plasma concentration
Measure: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
Safety Issue:
Description: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
Measure:Area under the plasma concentration versus time curve AUC from 0 to infinity (AUC0-inf)
Time Frame:up to 24 hours after CPL304110 administration
Safety Issue:
Description:AUC0-inf defines the area under the curve of plasma concentration vs time, from time point zero extrapolated to infinity
Measure:Terminal half-life (t½)
Time Frame:up to 24 hours after CPL304110 administration
Safety Issue:
Description:Plasma elimination half-life
Measure:Kel: Terminal elimination rate constant
Time Frame:up to 24 hours after CPL304110 administration
Safety Issue:
Description:Terminal elimination rate constant

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Celon Pharma SA

Trial Keywords

  • FGFR
  • kinase inhibitor
  • advanced solid tumors
  • carcinoma
  • neoplasms
  • gastric cancer
  • bladder cancer
  • squamous non-small cell lung cancer
  • squamous immunophenotype

Last Updated

June 8, 2020