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Neurofibromatosis and Malignant Peripheral Nerve Sheath TumorsPhase 1/2NCT05011019

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

A Phase 1/2 study testing AL2846 capsules in people with Neurofibromatosis and Malignant Peripheral Nerve Sheath Tumors, run by Chia Tai Tianqing Pharmaceutical Group Co., Ltd. at 1 site in China.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 to 75 years
What is being tested?
AL2846 capsules
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
22 participants
Where
1 siteChina
Study dates
7 Sep 2021to 2 Feb 2024
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
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  • 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:
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  • Blood routine examination standard (no blood transfusion and no hematopoietic stimulating factor drugs used for correction within 7 days before the examination):
  • White blood cell count (WBC) ≥3.5×109/L b. Hemoglobin (HGB) ≥90 g/L; c. The absolute value of neutrophils (NEUT) ≥ 1.5×109/L; d. Platelet count (PLT) ≥ 100×109/L.
  • The biochemical inspection shall meet the following standards:
  • Albumin (ALB) ≥35g/L; b. Total bilirubin (TBIL) ≤ 1.5× the upper limit of normal (ULN), and patients with Gilbert syndrome are ≤ 2.5× ULN; c. Alanine-based transferase (ALT) and aspartate-based transferase (AST) ≤2.5×ULN; d. Serum creatinine (CR) ≤1.5×ULN or creatinine clearance (CCR) ≥50ml/min (application of standard Cockcroft-Gault formula);
  • The coagulation function test shall meet the following standards:
  • International normalized ratio (INR)≤1.5×ULN (have not received anticoagulant therapy);
  • Thyroid function examination must meet the following standards:
  • Thyroid-stimulating hormone (TSH)≤ULN; if abnormal, Triiodothyronine （T3） and thyroxine（T4）levels should be examined, and T3 and T4 levels are normal.
  • 5. Heart color Doppler ultrasound assessment: Left ventricular ejection fraction (LVEF) ≥50%.
  • Female patients of childbearing age should agree to use contraceptive measures (such as intrauterine devices, contraceptives or condoms) during the study period and within 6 months after the end of the study; serum pregnancy test within 7 days before study entry Negative, and must be a non-lactating subject; male patients should agree to adopt avoidance measures during the study period and within 6 months after the end of the study period;
  • Patients enrolled in the second stage need to be pathologically confirmed to be enrolled in cohort 1, cohort 2 or cohort 3.

Who cannot join

  • Combined diseases and medical history:
  • 1. 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);
  • 2. With factors that affect oral medications (such as dysphagia, chronic diarrhea and intestinal obstruction, etc.)
  • 3. Unreliable toxic reactions higher than Common Terminology Criteria for Adverse Events(CTCAE) v5.0 level 1 caused by any previous treatment, excluding hair loss;
  • 4. Received major surgical treatment or obvious traumatic injury within 28 days before the first medication;
  • 5. Long-term unhealed wounds or fractures caused by surgery or trauma;
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  • 6. 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;
  • 7. With a history of psychotropic drug abuse and cannot be quit or have mental disorders;
  • 8. 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) ；
  • 9. Past or current retinal vein stenosis, retinal detachment, central retinal vein occlusion, glaucoma, grade 1 cataract, related symptoms caused by the disease are not considered as exclusion criteria;
  • 10. Interstitial pneumonia, including clinically significant radiation pneumonia;
  • 11. 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;
  • Renal failure requiring hemodialysis or peritoneal dialysis;
  • A history of immunodeficiency, including HIV positive or other acquired or congenital immunodeficiency diseases, or a history of organ transplantation;
  • Poor diabetes control (fasting blood glucose (FBG)> 10 mmol/L);
  • Urine routines suggest that urine protein is ≥++, and the 24-hour urine protein quantification is confirmed to be >1.0 g;
  • Those who suffer from epilepsy and need treatment;
  • Tumor-related symptoms and treatment:
  • 1. Have received surgery, chemotherapy, radiotherapy or other anti-cancer therapies within 4 weeks before the first medication (the washout period will be calculated from the end of the last treatment); Note: Those who have received local radiotherapy in the past can be included in the group if the following conditions are met: the end of radiotherapy is more than 4 weeks from the beginning of the study treatment (brain radiotherapy is more than 2 weeks); and the target lesion selected for this study is not in the radiotherapy area; Or the target lesion is located in the radiotherapy area, but the progress has been confirmed.
  • 2. Have received National Medical Products Administration(NMPA) approved Chinese patent medicines with anti-tumor indications (including compound cantharidin capsules, Kangai injections, Kanglaite capsules/injections, Aidi injections, Brucea javanica oil injections). /Capsules, Xiaoaiping Tablets/Injections, Huachansu Capsules, etc.) treatment;
  • Research and treatment related:
  • Patients who have previously received one of the following treatments:
  • Patients who have received NF1 drug treatment within 3 months before enrollment, and the related side effects have not yet recovered to below grade 1 (except for hair loss). Note: Patients who are receiving NF1 drug treatment must recover from the acute toxicity of the current NF1 treatment to less than or equal to Grade 1 (refer to CTCAE v5.0) before entering this study; b. Patients Received tipifarnib, pirfenidone, peg-interferon, sorafenib or other VEGFR inhibitor or biological treatments within 14 days before receiving study drug treatment ; c. Receiving strong Cytochrome P450 3A4 enzyme（CYP3A4） inhibitors (amprenavir, atazanavir, boceprevir, clarithromycin, cornivatan, delavirdine, diltiazem, erythromycin) within 14 days before receiving study drug treatment , Fursanavir, Indinavir, Itraconazole, Ketoconazole, Lopinavir, Mibefradil, Miconazole, Nefazodone, Nefinavir, Posaconazole, Ritonavir, saquinavir, tilarrevir, telithromycin, verapamil, voriconazole, etc.) or strong inducers (carbamazepine, felbamate, nevirapine, phenobarbital, phenytoin, Patients with primidone, rifabutin, rifampicin, rifapentin, etc.), except for external use on the skin;
  • Unable to perform Magnetic Resonance Imaging(MRI) examination and/or there are contraindications for MRI examination, such as prosthesis, orthotics or orthodontics, which will interfere with the volume analysis of the target Plexiform neurofibroma( PN) on MRI;
  • Patients who need to take more than the recommended dose of vitamin E daily;
  • Patients who have participated within 4 weeks before the first medication and used other anti-tumor clinical trial drugs or wihtin 5 half-lives;
  • According to the judgment of the investigator, there are situations that seriously endanger the safety of the patients or affect the completion of the study.

Trial locations and contacts

1 site in 1 country.

China1 site

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

    Shanghai, Shanghai Municipality, 200001

Other trials in China

About this study

Official title: Phase Ib Clinical Trial to Evaluate the Safety and Efficacy of AL2846 Capsules in Chinese Patients With Type I Neurofibromatosis (Neurofibromatosis and Malignant Peripheral Nerve Sheath Tumors)

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).

Being tested
AL2846 capsules
Medical subject headings
Neurofibromatoses, Neurofibrosarcoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AL2846 capsulesDrug

    AL2846 is a multi-target receptor tyrosine kinase inhibitor.

Study groups in NCT05011019
Study groupRoleWhat they receive
AL2846 CapsulesExperimentalDuring 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.
Receives: Drug: AL2846 capsules

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Adverse event rate

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

    Measured: :Baseline up to 96 weeks

  2. objective response rate (ORR)

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

    Measured: Baseline up to 96weeks

Secondary outcomes (8)

  1. Phase II clinical recommended dose （RP2D）

    recommended dose of Phase II clinical trial

    Measured: Baseline up to 96 weeks

  2. Progression-free survival (PFS)

    PFS defined as the time from randomization until the first documented progressive disease (PD) or death from any cause.

    Measured: up to 96 weeks

  3. Duration of Response (DOR)

    The time when the participants first achieved complete or partial remission to disease progression.

    Measured: up to 96 weeks

  4. PFS rate of one year

    Rate of patients with PFS reaching one year among all patients

    Measured: up to 96 weeks

  5. Overall Survival（OS）

    From date of first administration of test drug until the date of death from any cause

    Measured: assessed up to100 months

  6. Pain Scale (self-report form)

    Self-report of pain in target tumor and other parts of body

    Measured: up to 96 weeks

  7. Quality of life related scale（European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire version 3.0, EORTC QLQ-C30(V3)）

    Questionnaires about the quality of life (including mental state, appetite state, sleep, etc.)

    Measured: up to 96 weeks

  8. The patient's overall impression of the severity of symptoms (self-report)

    Self-report on the severity of tumor pain, overall pain status, and tumor-related problems other than pain (vision, hearing, mobility, hearing, appearance, etc.)

    Measured: up to 96 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Aug 2021
  2. Study start7 Sep 2021
  3. Primary completion2 Feb 2024
  4. Study completion2 Feb 2024

Why it stopped: sponsor adjusts its research and development strategy

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
22 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05011019
Sponsor's protocol ID
AL2846-Ib-01
Status last verified
Mar 2024
First submitted
10 Aug 2021
Last updated
21 Mar 2024
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing AL2846 capsules in people with Neurofibromatosis and Malignant Peripheral Nerve Sheath Tumors, run by Chia Tai Tianqing Pharmaceutical Group Co., Ltd. at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 27 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 21 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: sponsor adjusts its research and development strategy). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Adverse event rate (time frame: :Baseline up to 96 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05011019.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Mar 2024.

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