A Clinical Trial to Evaluate the Safety and Efficacy of AL2846 Capsules in Chinese Patients With Type I Neurofibromatosis

NCT05011019 | Terminated Phase 1

• 1 other identifier: AL2846-Ib-01
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

AL2846 is a multi-target receptor tyrosine kinase inhibitor. The purpose of this study is to evaluate the safety and efficacy of AL2846 capsules in Chinese patients with type I neurofibromatosis (NF1) (neurofibromas and malignant peripheral nerve sheath tumors).

Conditions

Neurofibromatosis and Malignant Peripheral Nerve Sheath Tumors

Outcome Measures

Primary Outcomes (2)

• Adverse event rate

  The occurrence of all adverse events (AEs), serious adverse events (SAEs) and treatment-related adverse events (TEAEs)

  :Baseline up to 96 weeks

• objective response rate (ORR)

  Percentage of participants achieving complete response (CR) and partial response (PR).

  Baseline up to 96weeks

Secondary Outcomes (8)

• Phase II clinical recommended dose （RP2D）

  Baseline up to 96 weeks

• Progression-free survival (PFS)

  up to 96 weeks

• Duration of Response (DOR)

  up to 96 weeks

• PFS rate of one year

  up to 96 weeks

• Overall Survival（OS）

  assessed up to100 months

Study Arms (1)

AL2846 Capsules

EXPERIMENTAL

During the dose escalation phase, patients enrolled in the group will first receive a single fasting administration（AL2846 capsules 120-150mg，oral）. The observation period is 3 days. If dose-limited toxity (DLT) does not occur, they will continue to receive multiple consecutive fasting administrations (120mg-150mg，once a day，oral ),every 28 days as a treatment cycle. During the dose expansion phase, patients will receive multiple consecutive fasting administrations (AL2846 capsules，120mg-150mg, oral ), every 28 days as a treatment cycle.

Drug: AL2846 capsules

Interventions

AL2846 capsules DRUG

AL2846 is a multi-target receptor tyrosine kinase inhibitor.

AL2846 Capsules

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients who voluntarily join the study and sign the informed consent form;
• Aged 18 to 75 years (when signing informed consent); Eastern cooperative oncology group（ ECOG） score: ≤2 ; patients with malignant peripheral nerve sheath tumors （MPNST）who are expected to survive ≥12 weeks;
• NF1 patients (including patients with MPNST) who are judged by the investigator as incomplete surgical resection, require systemic treatment, and have measurable lesions;
• Note: NF1 diagnostic criteria meets at least one of the following:
• Genetic examination confirmation: test positive for NF1 germline mutation in a Clinical Laboratory Improvement Amendments （CLIA）-certified laboratory (positive NF1 germline mutation must be confirmed by the central laboratory of this project, or an NF1 mutation test report issued by a CLIA-certified laboratory;
• Clinical and imaging examination confirmation: According to the clinical National Institute of Health (NIH) consensus criteria, at least two of the following NF1 diagnostic criteria are met:
• Six or more café-au-lait macules (≥0.5cm in prepubertal patients or ≥1.5 cm in post pubertal patients)
• Freckling in axilla or groin
• ≥2 neurofibromas of any type, or ≥1 plexiform neurofibromas
• Optic glioma
• Two or more Lisch nodules
• A distinctive bony lesion (dysplasia of the sphenoid bone or dysplasia or thinning of long bone cortex)
• A first-degree relative with NF1
• \- Patients who are confirmed by direct measurement or according to the Response Evaluation Criteria in Solid Tumors（RECIST） 1.1 standard that there is at least one evaluable lesion, and the diameter of the lesion is greater than 3 cm, and the lesion can be seen in three consecutive sections;
• The main organs function well and meet the following standards:

You may not qualify if:

• Combined diseases and medical history:
• \. Patients who have other malignant tumors within 3 years before the first medication or are currently suffering from other malignancies. The following two situations can be enrolled: other malignant tumors treated by a single operation; achieving 5 consecutive years of disease-free survival (DFS);
• \. With factors that affect oral medications (such as dysphagia, chronic diarrhea and intestinal obstruction, etc.)
• \. Unreliable toxic reactions higher than Common Terminology Criteria for Adverse Events(CTCAE) v5.0 level 1 caused by any previous treatment, excluding hair loss;
• \. Received major surgical treatment or obvious traumatic injury within 28 days before the first medication;
• \. Long-term unhealed wounds or fractures caused by surgery or trauma;
• \. Arterial/venous thrombosis occurred within 6 months before the first medication, such as cerebrovascular accident (including temporary ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism;
• \. With a history of psychotropic drug abuse and cannot be quit or have mental disorders;
• \. There are risk factors for prolonging the corrected QT interval（QTc）interval, such as uncorrectable hypokalemia, hereditary long QT syndrome, or taking drugs that prolong the QTc interval (mainly class Ia, Ic, and III antiarrhythmic drugs) ；
• \. Interstitial pneumonia, including clinically significant radiation pneumonia;
• \. Patients with any severe and/or uncontrollable disease, including:
• Unsatisfactory blood pressure control (systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥100 mmHg);
• Suffering from grade ≥2 myocardial ischemia or myocardial infarction, arrhythmia (including male QTc ≥450 ms (male), QTc ≥470 ms (female)) and grade ≥2 congestive heart failure (New York Heart Association ( NYHA) classification, appendix 2);
• Active or uncontrolled serious infection (≥CTCAE v5.0 Grade 2 infection);
• Active hepatitis: hepatitis B reference: HBsAg is positive, and the HBV DNA test value exceeds the upper limit of normal; hepatitis C reference: HCV antibody is positive, and the HCV virus titer test value exceeds the upper limit of normal; Note: Those who meet the criteria for entry, hepatitis B surface antigen-positive or core antibody-positive patients, and hepatitis C patients need to continue antiviral therapy to prevent virus activation;

Sponsors & Collaborators

• Chia Tai Tianqing Pharmaceutical Group Co., Ltd.: lead

Study Sites (1)

Shanghai Ninth People's Hospital, School of Medicine, Shanghai JiaoTong University

Shanghai, Shanghai Municipality, 200001, China

Location

MeSH Terms

Conditions

Neurofibromatoses; Neurofibrosarcoma

Condition Hierarchy (Ancestors)

Neurofibroma; Nerve Sheath Neoplasms; Neoplasms, Nerve Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplastic Syndromes, Hereditary; Neurocutaneous Syndromes; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Fibrosarcoma; Neoplasms, Fibrous Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Sarcoma; Peripheral Nervous System Neoplasms; Nervous System Neoplasms; Peripheral Nervous System Diseases; Neuromuscular Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 10, 2021
• First Posted: August 18, 2021
• Study Start: September 7, 2021
• Primary Completion: February 2, 2024
• Study Completion: February 2, 2024
• Last Updated: March 21, 2024

Record last verified: 2024-03

Locations

CN (1)