NCT05004142

Brief Summary

This is a multicenter, open-label clinical study to evaluate the safety and antitumor activity of FCN-437c in combination with Fulvestrant for the treatment of post-menopausal female patients with ER+ and HER2- advanced breast cancer, FCN-437c in combination with Letrozole + Goserelin for the treatment of pre-menopausal female patients with ER+ and HER2- advanced breast cancer, and to evaluate the PK characteristics of the FCN-437c combination therapies. This study is consist of two cohorts, Cohort 1: FCN-437c in combination with Fulvestrant (1st or 2nd line treatment for postmenopausal ER+, HER2-advanced breast cancer); Cohort 2: FCN-437c in combination with Letrozole + Goserelin (1st line treatment for premenopausal ER+, HER2- advanced breast cancer). Thirty patients will be enrolled in each cohort, for a total of 60 patients. Tumor Assessment: Tumor evaluation will be performed every 8 weeks (±7 days) according to RECIST version 1.1 until disease progression, withdrawal of informed consent, or death; for patients who discontinue the drug due to toxicity, imaging evaluation is required until disease progression. End of Treatment and End of Study: End of Study (EOS) is defined as 2 years after the last patient's first dose or the end of treatment (whichever is earlier). At the end of the study, the investigator will decide whether the patients whose disease has not progressed shall continue taking FCN-437c and other combination agents or not based on clinical benefit. Cohort 1: Post-menopausal patients diagnosed with ER+, HER2- advanced breast cancer, who have not received prior systemic therapy for advanced breast cancer, or who have disease progression determined by imaging assessment during their 1st line endocrine therapy; Cohort 2: Pre-menopausal patients diagnosed with ER+, HER2- advanced breast cancer, who have not received prior systemic therapy for advanced breast cancer;

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
70

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Jun 2020

Typical duration for phase_2

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

Study Start

First participant enrolled

June 30, 2020

Completed
12 months until next milestone

First Submitted

Initial submission to the registry

June 15, 2021

Completed
2 months until next milestone

First Posted

Study publicly available on registry

August 13, 2021

Completed
5 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 30, 2021

Completed
1.5 years until next milestone

Study Completion

Last participant's last visit for all outcomes

June 30, 2023

Completed
Last Updated

August 13, 2021

Status Verified

June 1, 2021

Enrollment Period

1.5 years

First QC Date

June 15, 2021

Last Update Submit

August 5, 2021

Conditions

Breast Neoplasms

Keywords

ER-PositiveHER2-NegativeBreast Neoplasms

Outcome Measures

Primary Outcomes (1)

  • Overall response rate

    Overall response rate (ORR) of FCN-437c in combination of fulvestrant in post-menopausal patients and letrozole + goserelin in pre-menopausal patients based on RECIST 1.1

    through study completion, assessed up to 24 months

Secondary Outcomes (9)

  • Safety and tolerability of the combination therapy

    Up to 30 days after EOT

  • PFS

    through study completion, assessed up to 24 months

  • OS

    through study completion, assessed up to 24 months

  • 1-year overall survival rate

    through study completion, assessed up to 24 months

  • DOR

    through study completion, assessed up to 24 months

  • +4 more secondary outcomes

Study Arms (2)

FCN-437c with Fulvestrant

EXPERIMENTAL

FCN-437c 200mg, oral administration under fasting conditions, QD, for 21 days, with 7-day discontinuation, 28 days for 1 cycle; Fulvestrant, C1D1 and C1D15 and Day 1 of each cycle, 500mg/day, intramuscularly.

Drug: FCN-437c+Fulvestrant

FCN-437c in combination with Letrozole + Goserelin

EXPERIMENTAL

FCN-437c 200mg, oral administration under fasting conditions, QD, for 21 days, with 7-day discontinuation, 28 days for 1 cycle; Letrozole 2.5 mg, QD, for continuous dosing; Goserelin 3.6 mg, subcutaneously, once every 28 days.

Drug: FCN-437c+Letrozole+Goserelin

Interventions

FCN-437c+FulvestrantDRUG

FCN-437c 200mg, oral administration under fasting conditions, QD, for 21 days, with 7-day discontinuation, 28 days for 1 cycle; Fulvestrant, C1D1 and C1D15 and Day 1 of each cycle, 500mg/day, intramuscularly.

FCN-437c with Fulvestrant
FCN-437c+Letrozole+GoserelinDRUG

FCN-437c 200mg, oral administration under fasting conditions, QD, for 21 days, with 7-day discontinuation, 28 days for 1 cycle; Letrozole 2.5 mg, QD, for continuous dosing; Goserelin 3.6 mg, subcutaneously, once every 28 days.

FCN-437c in combination with Letrozole + Goserelin

Eligibility Criteria

Age18 Years+
Sexfemale(Gender-based eligibility)
Gender Eligibility DetailsA Multicenter, Open-label Phase II Clinical Study: Evaluation of the Antitumor Activity, Safety, and Pharmacokinetic Profile of FCN-437c in Combination with Fulvestrant or Letrozole + Goserelin in female patients with ER+, HER2- Advanced Breast Cancer
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Subjects are eligible to be included in the study only if they meet all of the following criteria:
  • Patients with advanced breast cancer diagnosed as ER+, HER2-; ER+ is defined as histologically or cytologically confirmed ER+ with positive nuclear staining of estrogen receptor tumor cells ≥ 1% by immunohistochemistry; HER2- is defined as histologically or cytologically confirmed HER2-, with a negative ISH test result or an IHC test result of 0, 1+, or 2+, and if the IHC test result is 2+, the ISH test result must be negative;
  • Criteria of menopausal status and prior treatment, and see Appendix 3 for definition of menopause:
  • Cohort 1 (FCN-437c in combination with Fulvestrant): post-menopausal patients with advanced breast cancer, who are not suitable for curative surgical resection or radiation therapy and have not previously received systemic therapy, or have disease progression supported by imaging evaluation during their first-line endocrine therapy (including anti-estrogen or aromatase inhibitors).
  • Cohort 2 (FCN-437c in combination with Letrozole + Goserelin): pre-menopausal patients with advanced breast cancer, who are not suitable for curative surgical resection or radiation therapy and have not received systemic therapy; Note: If any relapse or metastases occur within 12 months from the treatment start during the (neo) adjuvant endocrine therapy or within 12 months after the (neo) adjuvant endocrine therapy, such (neo) adjuvant endocrine therapy will be taken as one line of systemic therapy.
  • ECOG (Eastern Cooperative Oncology Group) performance status score at 0 or 1;
  • According to RECIST 1.1, patients must have at least one measurable lesion ( for any lesion received radiotherapy or other local treatments, it may be considered as a measurable lesion if disease progression is proved by radiographic evidence after completion of treatment).
  • Note: Patients with only bone metastases must have at least one bone lesion that is predominantly osteolytic if no measurable lesion is present (for patients with no measurable lesion and only one osteolytic lesion, if prior radiotherapy to that lesion was performed, it is eligible if radiographic evidence supports disease progression of this bone lesion after radiotherapy).
  • Life expectancy for at least 12 weeks;
  • The bone marrow and organ function of the patient should be adequate:
  • Absolute neutrophil count ≥1.5×109/L;
  • Hemoglobin ≥ 90 g/L (without erythrocyte transfusion in 14 days);
  • Platelets ≥75×109/L;
  • Serum total bilirubin ≤1.5×ULN (upper limit normal), and ≤3.0×ULN for patients with Gilbert's syndrome;
  • AST (aspartate aminotransferase), ALT(alanine aminotransferase) ≤2.5×ULN; for patients with liver metastasis, both AST and ALT should be ≤5×ULN;
  • +3 more criteria

You may not qualify if:

  • Patients that meet any of the following conditions shall not be included in this clinical study:
  • Prior treatment criteria:
  • Prior treatment with a CDK4/6 inhibitor;
  • Prior systemic chemotherapy for advanced breast cancer;
  • Prior radiotherapy, major surgery, immunotherapy, monoclonal antibody therapy and other systemic anti-tumor therapy within 4 weeks before initiation of study drug administration;
  • Cohort 1:
  • i. (a) Previously received two or more lines of endocrine therapy; If relapse or metastases occur within 12 months from the treatment start during the (neo) adjuvant endocrine therapy or within 12 months after the (neo) adjuvant endocrine therapy, such (neo) adjuvant endocrine therapy will be taken as one line of systemic therapy; ii. Previously received Fulvestrant as first-line endocrine therapy for advanced breast cancer; e) Cohort 2: i. Previously treated with systemic anti-tumor therapy including endocrine therapy for advanced breast cancer; Note: Patients with disease progression after more than 12 months from the initiation or completion of the (neo) adjuvant therapy are eligible; Patients received Tamoxifen or an aromatase inhibitor within 14 days or an LHRH analogue within 28 days are eligible.
  • Patients unsuitable for endocrine therapy due to metastases to any important organ or with large tumor loads, e.g., patients judged by the investigator to be unsuitable for endocrine therapy:
  • symptomatic visceral metastases;
  • rapid disease progression or impaired visceral functions;
  • Non-visceral metastases requiring chemotherapy based on the investigator's clinical judgment;
  • Failure to recover from toxic effects of prior anti-tumor therapy (\> grade 2 as defined by NCI-CTCAE version 5.0);
  • Receipt strong CYP3A inhibitors (amprenavir, atazanavir, boceprevir, clarithromycin, conivaptan, delavirdine, diltiazem, erythromycin, fosamprenavir, indinavir, itraconazole, ketoconazole, lopinavir, mibefradil, miconazole, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, verapamil, voriconazole, etc.) or strong CYP3A inducers (carbamazepine, felbamate, nevirapine, phenobarbital, phenytoin, primidone, rifabutin, rifampin, rifapentine, etc.) within 14 days before the first dose;
  • Cardiac function and diseases that meet one of the following conditions:
  • lead electrocardiogram (ECG) measurements at the study site during the screening period, with a QTcF \> 470 ms based on the QTcF formula;
  • +13 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Fourth Hospital of Hebei Medical University

Shijiazhuang, Hebei, China

RECRUITING

Related Publications (4)

  • Slamon DJ, Neven P, Chia S, Fasching PA, De Laurentiis M, Im SA, Petrakova K, Bianchi GV, Esteva FJ, Martin M, Nusch A, Sonke GS, De la Cruz-Merino L, Beck JT, Pivot X, Vidam G, Wang Y, Rodriguez Lorenc K, Miller M, Taran T, Jerusalem G. Phase III Randomized Study of Ribociclib and Fulvestrant in Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: MONALEESA-3. J Clin Oncol. 2018 Aug 20;36(24):2465-2472. doi: 10.1200/JCO.2018.78.9909. Epub 2018 Jun 3.

    PMID: 29860922BACKGROUND

  • Im SA, Lu YS, Bardia A, Harbeck N, Colleoni M, Franke F, Chow L, Sohn J, Lee KS, Campos-Gomez S, Villanueva-Vazquez R, Jung KH, Chakravartty A, Hughes G, Gounaris I, Rodriguez-Lorenc K, Taran T, Hurvitz S, Tripathy D. Overall Survival with Ribociclib plus Endocrine Therapy in Breast Cancer. N Engl J Med. 2019 Jul 25;381(4):307-316. doi: 10.1056/NEJMoa1903765. Epub 2019 Jun 4.

    PMID: 31166679BACKGROUND

  • Sledge GW Jr, Toi M, Neven P, Sohn J, Inoue K, Pivot X, Burdaeva O, Okera M, Masuda N, Kaufman PA, Koh H, Grischke EM, Frenzel M, Lin Y, Barriga S, Smith IC, Bourayou N, Llombart-Cussac A. MONARCH 2: Abemaciclib in Combination With Fulvestrant in Women With HR+/HER2- Advanced Breast Cancer Who Had Progressed While Receiving Endocrine Therapy. J Clin Oncol. 2017 Sep 1;35(25):2875-2884. doi: 10.1200/JCO.2017.73.7585. Epub 2017 Jun 3.

    PMID: 28580882BACKGROUND

  • Cristofanilli M, Turner NC, Bondarenko I, Ro J, Im SA, Masuda N, Colleoni M, DeMichele A, Loi S, Verma S, Iwata H, Harbeck N, Zhang K, Theall KP, Jiang Y, Bartlett CH, Koehler M, Slamon D. Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): final analysis of the multicentre, double-blind, phase 3 randomised controlled trial. Lancet Oncol. 2016 Apr;17(4):425-439. doi: 10.1016/S1470-2045(15)00613-0. Epub 2016 Mar 3.

    PMID: 26947331BACKGROUND

Related Links

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by SiteNeoplasmsBreast DiseasesSkin DiseasesSkin and Connective Tissue Diseases

Study Officials

  • Yunjiang Liu, Doctor

    Hebei Medical University Fourth Hospital

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Yunjiang Liu, Doctor

CONTACT

13703297890lyj818326@126.com

Meiqi Wang, Master

CONTACT

18633051639maggie92320@hotmail.com

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 15, 2021

First Posted

August 13, 2021

Study Start

June 30, 2020

Primary Completion

December 30, 2021

Study Completion

June 30, 2023

Last Updated

August 13, 2021

Record last verified: 2021-06

Data Sharing

IPD Sharing
Will not share

Locations

CN(1)