NCT03420079

Brief Summary

This phase I trial with dose-escalation stage and dose-expansion stage is the first-in-human study of FCN-411, a drug being developed for treatment of advanced cancers. The initial purpose of the study is to determine the maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D) of FCN-411 monotherapy in EGFR-positive mutation non-small cell lung cancer chinese patients. The study will also provide early information on how the body handles the drug (pharmacokinetics) and on the anti-tumor activities of FCN-411.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
90

participants targeted

Target at P75+ for phase_1 lung-cancer

Timeline
Completed

Started Aug 2018

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 14, 2017

Completed
3 months until next milestone

First Posted

Study publicly available on registry

February 5, 2018

Completed
6 months until next milestone

Study Start

First participant enrolled

August 1, 2018

Completed
2.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2020

Completed
12 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 20, 2021

Completed
Last Updated

July 16, 2020

Status Verified

July 1, 2020

Enrollment Period

2.4 years

First QC Date

November 14, 2017

Last Update Submit

July 14, 2020

Conditions

Lung Cancer

Keywords

advanced NSCLCEGFR-TKI refractory

Outcome Measures

Primary Outcomes (8)

  • Cmax of FCN-411 following single dose.

    Cmax of FCN-411 following single dose.

    PK blood samples are collected at pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 120 hours post-dose.

  • AUC of FCN-411 following single dose.

    AUC of FCN-411 After Single Dosing.

    PK blood samples are collected at pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 120 hours post-dose.

  • Cmax of FCN-411 following multiple dosing.

    Cmax of FCN-411 After multiple dosing.

    The datas should be evaluated multiple times on the eighth day、fifteenth day of Cycle 1, first day、second day of Cycle 2. Each cycle is 21 days.

  • AUC of FCN-411 following multiple dosing.

    AUC of FCN-411 After Multiple Dosing.

    The datas should be evaluated multiple times on the eighth day、fifteenth day of Cycle 1, first day、second day of Cycle 2. Each cycle is 21 days.

  • Tmax of FCN-411 following single dose.

    Tmax of FCN-411 following single dose.

    PK blood samples are collected at pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 120 hours post-dose.

  • Tmax of FCN-411 following multiple dosing.

    Tmax of FCN-411 following multiple dosing.

    The datas should be evaluated multiple times on the eighth day、fifteenth day of Cycle 1, first day、second day of Cycle 2. Each cycle is 21 days.

  • t1/2 of FCN-411 following single dose.

    t1/2 of FCN-411 following single dose.

    PK blood samples are collected at pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 120 hours post-dose.

  • t1/2 of FCN-411 following multiple dosing

    t1/2 of FCN-411 following multiple dosing

    The datas should be evaluated multiple times on the eighth day、fifteenth day of Cycle 1, first day、second day of Cycle 2. Each cycle is 21 days.

Study Arms (2)

Dose escalation cohort of FCN-411

EXPERIMENTAL

* FCN-411 will be orally administrated at five sequential dose levels, which are 4 mg, 8 mg, 16 mg, 24 mg, and 32 mg. * Patients must be diagnosed with locally advanced or metastatic NSCLC who have progressed following prior therapy with an EGFR TKI agent (+/- additional chemotherapy regimens). * Participants will receive FCN-411 monotherapy once daily (QD) for sequential 21-day cycles.

Drug: FCN-411 Dose-escalation

Dose expansion cohort of FCN-411

EXPERIMENTAL

* FCN-411 will be orally administrated at MTD. * Patients must be diagnosed with locally advanced or metastatic NSCLC who have progressed following prior therapy with an EGFR TKI agent (+/- additional chemotherapy regimens). * Participants will receive FCN-411 monotherapy once daily (QD) for sequential 21-day cycles.

Drug: FCN-411 Dose-expansion

Interventions

FCN-411 Dose-escalationDRUG

* FCN-411 is a pan EGFR inhibitor, which has strong activity against wild type (WT), HER2, HER4 and EGFR sensitive mutations (including but not limited to T790M and L858R mutation). * FCN-411 shows significant antitumor activity in a dose-dependent manner in in vivo models of lung cancer, esophageal cancer and pharyngeal squamous cell carcinoma mediated by EGFR.

Also known as: EGFR-TKI
Dose escalation cohort of FCN-411
FCN-411 Dose-expansionDRUG

* FCN-411 is a pan EGFR inhibitor, which has strong activity against wild type (WT), HER2, HER4 and EGFR sensitive mutations (including but not limited to T790M and L858R mutation). * FCN-411 shows significant antitumor activity in a dose-dependent manner in in vivo models of lung cancer, esophageal cancer and pharyngeal squamous cell carcinoma mediated by EGFR.

Also known as: EGFR-TKI
Dose expansion cohort of FCN-411

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age 18 years and older.
  • Histological or cytological confirmed diagnosed advanced or metastatic NSCLC.
  • Documentation of disease progression while on previous continuous treatment with first-line EGFR TKI; patients must have confirmation of tumor EGFR activating mutations (exon 19 del, or exon 21 ins) and T790M status by biopsy sample or optical microscopy.
  • Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG).
  • Have a life expectancy of at least 12 weeks.
  • Have measurable disease based on RECIST v1.1. Note: previously irradiated not chosen, unless disease progression after irradiation.
  • Adequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values:
  • Neutrophils (absolute value) ≥ 1.5×10\^9/L;
  • Hemoglobin ≥ 90 g/L;
  • Platelet ≥ 90×10\^9/L;
  • Serum total bilirubin ≤ 1.5× ULN（for Patients with Gilbert Syndrome, total bilirubin ≤ 3×ULN and bilirubin ≤ 1.5×ULN should be permitted）
  • Aspartate aminotransferase、alanine aminotransferase ≤ 2.5×ULN; for patients with hepatic metastases, AST、ALT ≤ 5×ULN;
  • Creatinine \< 1.5×ULN creatinine clearance rate≥ 45 mL/min (Cockcroft Gault for calculating)
  • Female subjects have a negative urine or serum pregnancy.

You may not qualify if:

  • Treatment with any of the following:
  • Treatment with an EGFR TKI within 14 days or about 5 half-lives, whichever is the longer, of the first dose of study drug;
  • Any cytotoxic chemotherapy, investigational agents or anticancer drugs for the treatment from a previous treatment regimen within 14 days of the first dose of study treatment;
  • Major surgery within 4 weeks of the first dose of study treatment;
  • Systemic irradiation including whole brain irradiation;
  • Previously treated by EGFR-TKI for T790M (for example Osimertinib).
  • P-glycoprotein inducers (for example Rifampicin) or inhibitors (for example ritonavir) are required during the study.
  • Any unresolved toxicities from prior therapy greater than CTCAE grade 1 at the time of starting study treatment with the exception of alopecia and grade 2, prior platinum-therapy related neuropathy.
  • Meningeal metastases or CNS metastasis received intervention or malignancy related epilepsy; brain metastases without symptom are eligible.
  • Any serious or uncontrolled systemic disease, including but not limited to:
  • Uncontrolled hypertension;
  • Active hemorrhage;
  • Active infections including hepatitis B, or hepatitis C;
  • Human immunodeficiency virus positive;
  • Child Pugh C;
  • +18 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Cancer hospital chinese academy fo medical scienced

Beijing, 100021, China

RECRUITING

Related Publications (8)

  • Sequist LV, Yang JC, Yamamoto N, O'Byrne K, Hirsh V, Mok T, Geater SL, Orlov S, Tsai CM, Boyer M, Su WC, Bennouna J, Kato T, Gorbunova V, Lee KH, Shah R, Massey D, Zazulina V, Shahidi M, Schuler M. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol. 2013 Sep 20;31(27):3327-34. doi: 10.1200/JCO.2012.44.2806. Epub 2013 Jul 1.

    PMID: 23816960RESULT

  • Wu YL, Zhou C, Hu CP, Feng J, Lu S, Huang Y, Li W, Hou M, Shi JH, Lee KY, Xu CR, Massey D, Kim M, Shi Y, Geater SL. Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer harbouring EGFR mutations (LUX-Lung 6): an open-label, randomised phase 3 trial. Lancet Oncol. 2014 Feb;15(2):213-22. doi: 10.1016/S1470-2045(13)70604-1. Epub 2014 Jan 15.

    PMID: 24439929RESULT

  • Yang JC, Shih JY, Su WC, Hsia TC, Tsai CM, Ou SH, Yu CJ, Chang GC, Ho CL, Sequist LV, Dudek AZ, Shahidi M, Cong XJ, Lorence RM, Yang PC, Miller VA. Afatinib for patients with lung adenocarcinoma and epidermal growth factor receptor mutations (LUX-Lung 2): a phase 2 trial. Lancet Oncol. 2012 May;13(5):539-48. doi: 10.1016/S1470-2045(12)70086-4. Epub 2012 Mar 26.

    PMID: 22452895RESULT

  • Soria JC, Felip E, Cobo M, Lu S, Syrigos K, Lee KH, Goker E, Georgoulias V, Li W, Isla D, Guclu SZ, Morabito A, Min YJ, Ardizzoni A, Gadgeel SM, Wang B, Chand VK, Goss GD; LUX-Lung 8 Investigators. Afatinib versus erlotinib as second-line treatment of patients with advanced squamous cell carcinoma of the lung (LUX-Lung 8): an open-label randomised controlled phase 3 trial. Lancet Oncol. 2015 Aug;16(8):897-907. doi: 10.1016/S1470-2045(15)00006-6. Epub 2015 Jul 5.

    PMID: 26156651RESULT

  • Miller VA, Hirsh V, Cadranel J, Chen YM, Park K, Kim SW, Zhou C, Su WC, Wang M, Sun Y, Heo DS, Crino L, Tan EH, Chao TY, Shahidi M, Cong XJ, Lorence RM, Yang JC. Afatinib versus placebo for patients with advanced, metastatic non-small-cell lung cancer after failure of erlotinib, gefitinib, or both, and one or two lines of chemotherapy (LUX-Lung 1): a phase 2b/3 randomised trial. Lancet Oncol. 2012 May;13(5):528-38. doi: 10.1016/S1470-2045(12)70087-6. Epub 2012 Mar 26.

    PMID: 22452896RESULT

  • Katakami N, Atagi S, Goto K, Hida T, Horai T, Inoue A, Ichinose Y, Koboyashi K, Takeda K, Kiura K, Nishio K, Seki Y, Ebisawa R, Shahidi M, Yamamoto N. LUX-Lung 4: a phase II trial of afatinib in patients with advanced non-small-cell lung cancer who progressed during prior treatment with erlotinib, gefitinib, or both. J Clin Oncol. 2013 Sep 20;31(27):3335-41. doi: 10.1200/JCO.2012.45.0981. Epub 2013 Jul 1.

    PMID: 23816963RESULT

  • Wong AL, Sundar R, Wang TT, Ng TC, Zhang B, Tan SH, Soh TI, Pang AS, Tan CS, Ow SG, Wang L, Mogro J, Ho J, Jeyasekharan AD, Huang Y, Thng CH, Chan CW, Hartman M, Iau P, Buhari SA, Goh BC, Lee SC. Phase Ib/II randomized, open-label study of doxorubicin and cyclophosphamide with or without low-dose, short-course sunitinib in the pre-operative treatment of breast cancer. Oncotarget. 2016 Sep 27;7(39):64089-64099. doi: 10.18632/oncotarget.11596.

    PMID: 27577069RESULT

  • Lin L, Pan H, Li X, Zhao C, Sun J, Hu X, Zhang Y, Wang M, Ren X, Luo X, Shan G, Hui AM, Wu Z, Liu H, Tian L, Shi Y. A phase I study of FCN-411, a pan-HER inhibitor, in EGFR-mutated advanced NSCLC after progression on EGFR tyrosine kinase inhibitors. Lung Cancer. 2022 Apr;166:98-106. doi: 10.1016/j.lungcan.2022.01.025. Epub 2022 Feb 3.

    PMID: 35248866DERIVED

Related Links

MeSH Terms

Conditions

Lung Neoplasms

Condition Hierarchy (Ancestors)

Respiratory Tract NeoplasmsThoracic NeoplasmsNeoplasms by SiteNeoplasmsLung DiseasesRespiratory Tract Diseases

Study Officials

  • Yuankai Shi, MD

    Cancer Institute and Hospital, Chinese Academy of Medical Sciences

    PRINCIPAL INVESTIGATOR

Central Study Contacts

yuankai Shi, MD

CONTACT

010-87788298syuankaipumc@126.com

xingsheng hu, MD

CONTACT

010-87788298huxingsheng66@163.com

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Model Details: In the dose escalation cohort of FCN-411, the dose will be escalated from 4 mg, 8 mg, 16 mg, 24 mg to 32 mg. The MTD will be expanded to ascertain the RP2D.
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 14, 2017

First Posted

February 5, 2018

Study Start

August 1, 2018

Primary Completion

December 31, 2020

Study Completion

December 20, 2021

Last Updated

July 16, 2020

Record last verified: 2020-07

Locations

CN(1)