To Evaluate the Efficacy, Safety, and PK Characteristics of FCN-159 in Pediatric Patients With Refractory/Recurrent LCH

NCT05997602 | Recruiting Phase 2

• 1 other identifier: FCN-159-004
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 11

Brief Summary

This is a rare disease, single-arm, open-label,multi-center, non-randomized Phase 2 clinical study to evaluate the efficacy, safety, and pharmacokinetic characteristics of FCN-159 monotherapy in pediatric patients with refractory/recurrent Langerhans cell histiocytosis (LCH).

Conditions

Langerhans Cell Histiocytosis; LCH

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR) Evaluated by Independent Review Committee (IRC) Based on PET Response Criteria (PRC)

  ORR Evaluated by Independent Review Committee (IRC) Based on PET Response Criteria (PRC) is defined as the percentage of participants who achieved a best overall response of CMR or PMR assessed by IRC .

  up to 24months

Secondary Outcomes (12)

• Objective Response Rate (ORR) Evaluated by Investigator Based on PET Response Criteria (PRC) and Langerhans Cell Histiocytosis Evaluation and Treatment Guidelines (Histiocyte Society, April 2009, hereinafter referred to as "Guidelines")

  up to 24months

• Disease Control Rate (DCR) Evaluated by Investigator Based on PET Response Criteria (PRC) and "Guidelines".

  up to 24months

• Clinical benefit rate (CBR) Evaluated by Investigator Based on PRC and "Guidelines".

  up to 24months

• Time to Response (TTR) Evaluated by Investigator Based on PET Response Criteria (PRC) and "Guidelines"

  up to 24months

• One-year Progressive Free Survival (PFS) Rate Evaluated by Investigator Based on PET Response Criteria (PRC) and "Guidelines"

  up to 12months

Study Arms (1)

FCN-159

EXPERIMENTAL

Experimental: FCN-159 Dosage form:tablet Specification: 1mg，4mg Dose: FCN-159 5mg/m² (Maximum dose does not exceed 8mg), orally, once daily

Drug: FCN-159

Interventions

FCN-159 DRUG

5mg/m² (Maximum dose does not exceed 8mg, the recommended oral dose for adults), orally, once daily, continuously for 28 days per cycle.

FCN-159

Eligibility Criteria

• Age: 2 Years - 16 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age 2-16 (inclusive)
• Patients with histologically confirmed Langerhans cell histiocytosis (LCH) diagnosed by the central laboratory.
• If sufficient tumor tissue samples and peripheral blood samples are available, central laboratory biomarker testing is required as follows: including but not limited to ERBB3, BRAF, ARAF, HRAS, KRAS, NRAS, MEK (MAP2K1 and MAP2K2), and other MEK upstream genes.If inability to get tissue, the gene testing results from a local laboratory also can be accepted.
• Patients who have received at least prior first-line systemic treatment, defined as treatment including vinblastine (VBL) and glucocorticoids for at least 2 weeks. VBL can be substituted with vincristine (VCR) or vindesine (VDS). Alternatively, patients may be unable to tolerate chemotherapy due to severe chemotherapy toxicity. Inability to tolerate chemotherapy is defined as one of the following: Severe liver impairment (liver enzyme elevation ≥ 5 × upper limit of normal (ULN) and bilirubin elevation ≥ 1.5 × ULN), severe neurotoxicity related to vinca alkaloids, chemotherapy-related intracranial hypertension, or grade 4 bone marrow depression with severe infection (sepsis, severe pneumonia, etc.) after chemotherapy.
• Refractory/relapsed LCH is defined as the presence of one of the following:
• Failure of prior treatment, i.e., no regression in risk organs after at least 2 weeks of systemic treatment, or overall evaluation of AD-progression or AD-mix;
• Initial response of the disease to first or second-line systemic treatment is NAD or AD-better or AD-stable, followed by disease reactivation after maintenance therapy for more than 3 months. Second-line treatment includes cytarabine and/or cladribine.
• Persistent mutated gene positive in plasma free DNA testing during prior treatment (confirmed by 2 consecutive tests) or retest positive after treatment discontinuation;
• Lack of regression in the affected central nervous system (including the pituitary gland) after treatment;
• Presence of bone marrow involvement and/or hemophagocytic lymphohistiocytosis (HLH);
• Presence of evaluable lesions based on PET response criteria (PRC).
• Patients who have to have recovered from all acute toxic effects of prior anti-tumor therapy, and all relevant toxicities must be ≤ grade 1 (except for alopecia and ototoxicity).
• Expected survival at least ≥ 3 months;
• Lansky (≤ 15 years old) and Karnofsky (≥ 16 years old) performance status scores should be ≥ 50%, as shown in Appendix 4.
• Patients or their legal guardians must be able to understand and willingly sign a written informed consent form.

You may not qualify if:

• Patients who have received any of the following prior treatments:
• Chemotherapy, targeted therapy, immunotherapy, biologic therapy, or herbal anti-tumor therapy for LCH within 4 weeks or \< 5 half-lives (whichever is shorter)before the start of the study drug .
• Strong CYP3A4, CYP2C8, and CYP2C9 inhibitors or inducers within 14 days before the start of the study drug, except for topical skin application.
• Gowth factors that promote platelet or white blood cell count or function within 7 days before the start of the study drug.
• Radiotherapy or major surgical treatment (including craniotomy, thoracotomy, laparotomy, open bone or joint surgery, etc.) within 4 weeks before the start of the study drug.
• Participated in other interventional clinical trials within 4 weeks before the start of the study drug.
• MEK 1/2 inhibitors (those who have received this treatment for a short period of ≤ 2 weeks may be included).
• Anticoagulants within 7 days before the start of the study drug for patients with brain tumors (intracranial masses).
• Prednisone treatment \< 0.5mg/kg/day (or equivalent dose of other corticosteroids) is allowed within one month before enrollment, but must be discontinued 14 days before the start of the study drug. Patients with brain lesions receiving corticosteroid therapy for brain edema must maintain a stable dose for 14 days before enrollment. Hormone replacement therapy is allowed for patients with hypopituitarism due to primary disease involvement of the pituitary.
• Patients with a history of other malignant tumors or concurrent other malignant tumors (excluding cured non-melanoma skin basal cell carcinoma, ductal carcinoma in situ of the breast, or cervical carcinoma in situ).
• Uncontrolled hypertension (with medication treatment): Blood pressure (BP) greater than or equal to the 95th percentile for age, height, and sex, as described in Appendix 6.
• Patients with dysphagia, active gastrointestinal disease, malabsorption syndrome, or other conditions that may affect the absorption of the study drug.
• Prior or current history of retinal vein obstruction (RVO), retinal pigment epithelial detachment (RPED), glaucoma, and other clinically significant abnormal ophthalmologic examination results.
• Interstitial pneumonia, including clinically significant radiation pneumonitis. Except for interstitial pneumonia caused by pulmonary involvement of the primary disease.
• Patients will be excluded if their cardiac function or comorbidities meet any of the following criteria:

Sponsors & Collaborators

• Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd.: lead

Study Sites (11)

Beijing Children's Hospital, Capital Medical University

Beijing, Beijing Municipality, China

RECRUITING

Children's Hospital Affiliated to the Capital Institute of Pediatrics

Beijing, Beijing Municipality, China

NOT YET RECRUITING

Children's Hospital of Chongqing Medical University

Chongqing, Chongqing Municipality, China

RECRUITING

Sun Yat-Sen Memorial Hpsipital,Sun Yat-Sen Unniversity

Guangzhou, Guangdong, China

NOT YET RECRUITING

The First Affiliated Hospital,Sun Yat-sen University

Guangzhou, Guangdong, China

NOT YET RECRUITING

Shenzhen Children's Hospital

Shenzhen, Guangdong, China

NOT YET RECRUITING

Henan Children's Hospital Zhengzhou Children's Hospital

Zhengzhou, Henan, China

NOT YET RECRUITING

Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology

Wuhan, Hubei, China

NOT YET RECRUITING

West China Second University Hospital,Sihuan University/West China women's and Children's Hospital

Chengdu, Sichuan, China

NOT YET RECRUITING

Children's Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

NOT YET RECRUITING

Children's Hospital of Soochow University

Suzhou, China

NOT YET RECRUITING

MeSH Terms

Conditions

Histiocytosis, Langerhans-Cell

Condition Hierarchy (Ancestors)

Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Histiocytosis; Lymphatic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Rui Zhang, MD

  Beijing Children's Hospital,Captial Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rui Zhang, MD

CONTACT

18611106187; ruizh1973@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 8, 2023
• First Posted: August 18, 2023
• Study Start: September 28, 2023
• Primary Completion: May 14, 2025
• Study Completion (Estimated): May 14, 2027
• Last Updated: January 24, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (11)