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

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

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).

Study Phase

Phase 1

Study Type

Interventional

Primary Outcome

Maximum tolerated dose (MTD)

Secondary Outcome

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

Condition

Gastric Cancer

Intervention

CPL304110

Study Arms / Comparison Groups

 CPL304110

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

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status

Drug

Estimated Enrollment

Start Date

July 19, 2019

Completion Date

July 2021

Primary Completion Date

July 2021

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.

Gender

All

Ages

25 Years - N/A

Accepts Healthy Volunteers

No

Contacts

, +48 791 690 990, [email protected]

Location Countries

Poland

Location Countries

Poland

Administrative Informations

NCT ID

NCT04149691

Organization ID

01FGFR2018

Responsible Party

Sponsor

Study Sponsor

Celon Pharma SA

Collaborators

 National Center for Research and Development, Poland

Study Sponsor

, ,

Verification Date

October 2020