A Multicenter, Open, Single-arm Phase I Dose Exploration and Phase II Extended Study Was Conducted to Evaluate the Safety, Tolerability, Pharmacokinetic Characteristics, and Primary Antitumor Activity of FCN-011 in Patients With Advanced Solid Tumor (Phase I) and NTRK Fusion Positive Advanced Solid Tumor (Phase II)

Fochon Pharmaceuticals, Ltd.1 site in 1 country82 target enrollmentApril 13, 2021

ConditionsAdvanced Solid Tumor

InterventionsFCN-011

DrugsFCN-011

Overview

Phase: Phase 1
Intervention: FCN-011
Conditions: Advanced Solid Tumor
Sponsor: Fochon Pharmaceuticals, Ltd.
Enrollment: 82
Locations: 1
Primary Endpoint: To determine the occurrence of treatment-related adverse events meeting the criteria for dose limiting toxicities (DLTs)
Last Updated: 4 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

A multicenter, open, single-arm phase I dose exploration and phase II extended study was conducted to evaluate the safety, tolerability, pharmacokinetic characteristics, and primary antitumor activity of FCN-011 in patients with advanced solid tumor (phase I) and NTRK fusion positive advanced solid tumor (phase II)

Detailed Description

This study is a multicenter, open, single-arm Phase I/II clinical study, which is divided into two research parts, namely phase I dose exploration study and phase II dose extension study. In the phase I dose exploration study, the safety, tolerance and PK characteristics of FCN-011 in patients with advanced solid tumors were determined, the MTD of oral fCN-011 was determined, and the RP2D of FCN-011 in the phase II clinical study was determined, and the efficacy of FCN-011 was preliminarily evaluated. The phase II dose extension study evaluated the efficacy, safety, and tolerability of continuous oral ADMINISTRATION of FCN-011 in patients with inoperable NTRK fusion and advanced stage III or IV solid tumors, as well as the characteristics of population pharmacokinetics (PopPK). A total of 35-82 patients were enrolled in this study, 15-24 patients were expected to be enrolled in the phase I study, and 20-58 patients were expected to be enrolled in the phase II study.

Registry

clinicaltrials.gov

Start Date

April 13, 2021

End Date

March 31, 2024

Last Updated

4 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Fochon Pharmaceuticals, Ltd.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Age ≥ 16 years，no gender limitation；
•Patients with inoperable solid tumors, stage III or IV, confirmed histologically or cytologically by standard treatment failure or no standard treatment;
•Sufficient tumor tissue samples from clinical phase I patients shall be sent to the central laboratory for NTRK fusion gene test, and the results of the central laboratory will not affect the inclusion of subjects (if multiple patients are screened, patients with positive NTRK fusion gene or point mutation will be preferred to be included);
•Sufficient tumor tissue samples must be provided for phase II clinical patients, which will be confirmed to be positive for NTRK fusion gene by the method of 2-generation gene sequencing by the central laboratory designated by the sponsor;
•The ECOG Scores 0 or 1 for physical fitness (phase I),0-2(phase II) ;
•Can understand and be willing to sign informed consent prior to the commencement of any research procedure; Expected survival at least 12 weeks;
•Patients with adequate organ and bone marrow function: absolute value of neutrophils ≥ 1.0 × 10\^9/L (no G-CSF treatment within 7 days);Hemoglobin ≥ 80g/L (no erythrocyte infusion within 7 days);Platelet ≥ 75 × 10\^9/L; Serum total bilirubin ≤ 1.5 × upper limit normal (ULN), and patients with Gilbert syndrome ≤3.0 × ULN. Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤ 2.5 × ULN; For patients with liver metastasis, AST and ALT should be ≤ 5 × ULN. Creatinine\<1.5×ULN or Creatinine clearance was ≥ 60 ml/min in phase I patients, and ≥ 45ml/min in phase II patients. Creatinine clearance was calculated by Cockroft - Gault formula. Albumin ≥ 3g/dL;
•At least one evaluable lesion (stage I) was assessed according to RECIST 1.1 or RANO criteria; According to RECIST 1.1 or RANO standard to evaluate, at least one measurable lesions (phase II) (primary central nervous system tumors according to the standard definition RANO, needs to have one or more measurable lesions by MRI assessment, size for at least 10 mm or more, and appeared in two or more ≤ 5 mm thick section, the measure does not include cystic cavity.) The imaging evaluation should be completed within 28 days before enrollment, and the patient's hormone dosage should be stable for at least 5 days or more;
•A fertile woman must have a negative serum pregnancy test within 28 days of the first study drug administration and agree to contraception between 28 days before the first study drug administration and 30 days after the last study drug administration; Male patients are required to undergo ligation or agree to contraception and refuse sperm donation from 7 days before the first dose to 30 days after the last dose; The failure rate of contraceptive methods\<1% per year, such as double screen contraceptive methods, condoms, oral or injectable contraceptives.

Exclusion Criteria

•Patients who received targeted therapy within 2 weeks or within 5 half-lives (whichever is shorter) before starting administration, and who received chemotherapy, major surgery, radiotherapy, immunotherapy or clinical trials within 4 weeks or within 5 half-lives (which is shorter);
•Uncontrolled or symptomatic brain metastases (asymptomatic or stably controlled CNS metastases and no hormone therapy within 2 weeks are allowed to be enrolled);Patients with spinal cord metastasis with symptoms of spinal cord compression;Primary CNS tumors were allowed to be enrolled.
•The toxicity of previous anti-tumor therapy has not recovered (\>NCI-CITCAE 5.0 level 2), neurotoxic reaction level 2, except hair loss;
•Patients should use strong CYP3A4 inhibitors (except drugs permitted in Section 6.8), inducers or sensitive substrates and sensitive substrates of CYP2B6 at the same time;
•Patients take drugs (mainly Ia, Ic, class III anti-arrhythmia drugs) that will prolong the QTc interval or have risk factors for extending the QTc interval;
•Difficulty in swallowing, or having an absorbance syndrome, or other medical conditions that prevent the absorption of drugs through the intestinal tract, or affect the absorption of FCN-011;
•Cardiac function and disease meet one of the following conditions:
•（1）screening period in research center 3 times of 12 lead ECG measurement, according to the instrument of QTc formula for calculating the average three times, QTc\>470 ms;
•（2）continue uncontrolled hypertension, systolic blood pressure under antihypertensive treatment \>150 mmHg, and/or diastolic pressure \>100 mmHg；
•（3）the American New York Heart Association (New York Heart Association, NYHA) classification of grade 3 or more congestive Heart failure;

Arms & Interventions

Experimental: phase I dose exploration

FCN-011 will be given orally in ascending doses in patients with advanced solid tumor , until the maximum tolerated dose or recommended dose is reached.

Intervention: FCN-011

Outcomes

Primary Outcomes

To determine the occurrence of treatment-related adverse events meeting the criteria for dose limiting toxicities (DLTs)

Time Frame: 30 days

The recommended phase II dose for FCN-011

Time Frame: From first dose up to 30 days after last dose

Overall response rate (ORR) by Response Criteria in Solid Tumors (RECIST) v1.1

Time Frame: Baseline up to approximately 1 year

Secondary Outcomes

To quantify the occurrence of adverse events (AEs) reported in all subjects who received study drug(From enrollment up to 30 days after last dose)
the death of the last medicine occurred within 30 days of frequency and cause of death(From enrollment up to 30 days after last dose)
The occurrence of treatment-emergent adverse events (TEAs)(From enrollment up to 30 days after last dose)
To quantify the last time point with a quantifiable concentration (AUClast) of FCN-011 after administration as a single agen(2 months)
To measure the time to reach the highest plasma concentrations (Tmax) of FCN-011 after single agent administration(2 months)
To quantify the terminal half-life (T1/2) of FCN-011 after administration as a single agent(2 months)
To quantify the dose-dependent serum concentrations (Cmax) of FCN-011 as a single agent(2 months)