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Type I NeurofibromatosisPhase 1NCT05107037

A Clinical Trial to Evaluate the Tolerability and Pharmacokinetics of TQ-B3234 in Patients With Type I Neurofibromatosis

A Phase 1 study testing TQ-B3234 capsule in people with Type I Neurofibromatosis, run by Chia Tai Tianqing Pharmaceutical Group Co., Ltd. at 1 site in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

This study is a Phase I clinical trial to evaluate the tolerability and pharmacokinetics of TQ-B3234 capsules in Chinese subjects associated with neurofibromatosis type I (neurofibroma and peripheral malignant neurilemmoma). Two study phases were designed, including (1) dose escalation and (2) cohort expansion. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Type I Neurofibromatosis
What is being tested?
TQ-B3234 capsule
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
120 participants
Where
1 siteChina
Study dates
Nov 2021to Dec 2024
Phase
Phase 1
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 voluntarily join the study, Sign the informed consent form;
  • Aged: [18~75] years old (when signing informed consent); Eastern cooperative oncology group performance Status（ECOG PS )score: ≤2 points; patients with malignant peripheral nerve sheath tumors （MPNST）are expected to survive ≥12 weeks;
  • NF1 patients (including patients with malignant peripheral nerve sheath tumor (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 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 Institutes of Health(NIH) consensus criteria, at least two of the following seven 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
  • 4. 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;
  • 5. The main organs function well and meet the following standards:
  • 1) 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
  • Hemoglobin (HGB) ≥90 g/L;
  • The absolute value of neutrophils (NEUT) ≥ 1.5×109/L;
  • Platelet count (PLT) ≥ 100×109/L. 2) The biochemical inspection shall meet the following standards:
  • Albumin (ALB) ≥35g/L; b. Total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal (ULN), and patients with Gilbert syndrome are ≤ 2.5 times the upper limit of normal (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); 3) The coagulation function test shall meet the following standards: International normalized ratio (INR)≤1.5×ULN (have not received anticoagulant therapy); 4) Thyroid function examination must meet the following standards: Thyroid-stimulating hormone (TSH)≤ULN; if abnormal, T3 and T4 levels should be examined, and T3 and T4 levels are normal.
  • 5) Heart color Doppler ultrasound assessment: Left ventricular ejection fraction (LVEF) ≥50%.
  • 6. 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;
  • 7. 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

  • 1. Combined diseases and medical history:
  • Have other malignant tumors within 3 years before the first medication or is currently suffering from other malignancies The following two situations can be included in the group: other malignant tumors treated by a single operation, to achieve 5 consecutive years of disease-free survival (DFS);
  • Many 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;
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  • 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;
  • Have 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), such as uncorrectable hypokalemia, hereditary long QT syndrome, or taking drugs that prolong the QTc interval (mainly class Ia, Ic, and III antiarrhythmic drugs) ；
  • 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;
  • 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:hepatitis b surface antigen（HBsAg） is positive, and the DNA of hepatitis B virus(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;
  • 2. 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); 2) Have received 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;
  • 3. 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;
  • Patients Received tipifarnib, pirfenidone, peg-interferon, sorafenib or other Vascular Endothelial Growth Factor Receptor(VEGFR) inhibitor or biological treatments within 14 days before receiving study drug treatment ;
  • Receiving strong 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, rifapentine, etc.), except for external use on the skin;
  • Unable to perform Nuclear 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 neurofibromas( PN) on MRI;
  • Patients who need to take more than the recommended dose of vitamin E daily;
  • 4. Participated within 4 weeks before the first medication and used other anti-tumor clinical trial drugs or those who have not exceeded 5 drug half-lives;
  • 5. According to the judgment of the investigator, there are situations that seriously endanger the safety of the patients or affect the completion of the research by the patients.

Trial locations and contacts

1 site in 1 country.

Qingfeng Li, Doctor contact

021-2327169

dr.liqingfeng@shsmu.edu.cn

China1 site

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

    Shanghai, Shanghai Municipality, 200001

    Qingfeng Li, Doctor, 021-2327169, dr.liqingfeng@shsmu.edu.cn

Other trials in China

About this study

Official title: A Phase I Clinical Trial to Evaluate the Tolerability and Pharmacokinetics of TQ-B3234 Capsules in Chinese Patients With Type I Neurofibromatosis (Neurofibromatosis and Malignant Peripheral Nerve Sheath Tumors)

This study is a Phase I clinical trial to evaluate the tolerability and pharmacokinetics of TQ-B3234 capsules in Chinese subjects associated with neurofibromatosis type I (neurofibroma and peripheral malignant neurilemmoma).

Two study phases were designed, including (1) dose escalation and (2) cohort expansion.

The purpose of this study was to evaluate the tolerance, pharmacokinetic characteristics, efficacy and safety of TQ-B3234 capsule, and to explore the therapeutic biomarkers related to this product.

Being tested
TQ-B3234 capsule
Medical subject headings
Neurofibromatoses

What participants receive

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

  • TQ-B3234 capsuleDrug

    TQ-B3234 is an anti-tumor molecular targeted drug, which is a selective Mitogen-activated protein kinase kinase（MEK）1/2 inhibitor

Study groups in NCT05107037
Study groupRoleWhat they receive
TQ-B3234 capsuleExperimentalIn the dose escalation phase, enrolled subjects first received a single dose on an empty stomach for a 3-day observation period. If Dose limiting toxicity (DLT) did not occur, continuous multiple doses were continued, once a day on an empty stomach for a treatment cycle of 28 days. After the dose escalation phase was completed, cohort extension studies were conducted according to the identified phase ii clinical recommended doses.type I neurofibromatosis （NF1） patients and malignant peripheral nerve sheath tumors （MPNST） patients were selected.
Receives: Drug: TQ-B3234 capsule

What is being measured

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

  1. Maximum tolerated dose (MTD)

    If DLT occurs in 2 or more subjects in a given dose group, the dose level in the previous dose group is considered MTD

    Measured: Baseline up to 48weeks

  2. Dose limiting toxicity (DLT)

    Some drug-related toxicities occurred within 28 days of treatment

    Measured: Baseline up to 4 weeks

  3. Phase II clinical recommended dose （RP2D）

    Phase II clinical recommended dose

    Measured: Baseline up to 48 weeks

  4. objective response rate（ORR）

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

    Measured: Baseline up to 96 weeks

Secondary outcomes (18)

  1. Peak concentration (Cmax)

    Maximum plasma drug concentration

    Measured: Before administration, 10 , 20 , 30, 45 minuets, 1 , 2 , 4 , 6 , 10 , 24 , 48 , 72 hours after administration

  2. Peak time (Tmax)

    Time to maximum plasma concentration

    Measured: Before administration, 10 , 20 , 30, 45 minuets, 1 , 2 , 4 , 6 , 10 , 24 , 48 , 72 hours after administration

  3. Clearance half-life (t1/2)

    The time required for the concentration of a drug to fall by half in a living organism

    Measured: Before administration, 10 , 20 , 30, 45 minuets, 1 , 2 , 4 , 6 , 10 , 24 , 48 , 72 hours after administration

  4. Area under plasma concentration-time Curve (AUC)

    Area under plasma concentration-time Curve

    Measured: Before administration, 10 , 20 , 30, 45 minuets, 1 , 2 , 4 , 6 , 10 , 24 , 48 , 72 hours after administration

  5. Steady state clearance half-life (t1/2, SS)

    Steady state clearance half-life (t1/2, SS)

    Measured: Pre-dose of day 1, day 8, day 15, day 28 on multiple dose and 10 , 20 , 30 , 45 minutes,1 , 2 , 4 , 6 , 10 , 24 hours post-dose on multiple dose of day 1 and day 28

  6. Plasma concentration at steady state (Cav, SS)

    The plasma concentration at which the rate of administration and rate of elimination are in equilibrium

    Measured: Pre-dose of day 1, day 8, day 15, day 28 on multiple dose and 10 , 20 , 30 , 45 minutes,1 , 2 , 4 , 6 , 10 , 24 hours post-dose on multiple dose of day 1 and day 28

  7. Area under plasma concentration-time curve at steady state (AUCss)

    Area under plasma concentration-time curve at steady state

    Measured: Pre-dose of day 1, day 8, day 15, day 28 on multiple dose and 10 , 20 , 30 , 45 minutes,1 , 2 , 4 , 6 , 10 , 24 hours post-dose on multiple dose of day 1 and day 28

  8. Coefficient of fluctuation (DF)

    Coefficient of fluctuation

    Measured: Pre-dose of day 1, day 8, day 15, day 28 on multiple dose and 10 , 20 , 30 , 45 minutes,1 , 2 , 4 , 6 , 10 , 24 hours post-dose on multiple dose of day 1 and day 28

  9. Adverse event rate

    The occurrence of all adverse events (AE), serious adverse events (SAE) and treatment-related adverse events (TEAEs)

    Measured: Baseline up to 96 weeks

  10. 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

  11. Duration of Response (DOR)

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

    Measured: up to 96 weeks

  12. Disease Control Rate (DCR)

    The proportion of patients whose tumor shrank or remained stable for some time, including those with complete response (CR), partial response (PR), and stable (SD).

    Measured: up to 96 weeks

  13. 1 year PFS rate

    Rate of patients with PFS reaching 1 year among all patients

    Measured: up to 1 year

  14. Overall survival time (OS, observed only in peripheral malignant schwannomas)

    The time between the start of treatment and death directly due to the disease.

    Measured: up to 5 year

  15. Effects on pain score in subjects

    Questionnaire: pain score：The line segments below all have numbers from 0 to 10, where 0 means no pain and 10 is the worst pain you can imagine.

    Measured: up to 96 weeks

  16. Effects on subjects' health-related quality of life

    Questionnaire: Quality of life related scale（The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 3rd edition）.For questions 1 to 28, choose a number from 1 to 4. 1 means none and 4 means very.For questions 29 and 30, choose a number from 1 to 7, with 1 being very poor and 7 being very good.

    Measured: up to 96 weeks

  17. Effects on subjects' related symptoms

    Patients' overall impression of severity of cancer symptoms (self-reported)

    Measured: up to 96 weeks

  18. Effects on pain interference index in subjects

    Questionnaire: pain interference index：Please answer each one by circling a number from 0 to 6, where 0 means none at all and 6 means completely

    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 posted4 Nov 2021
  2. Study startNov 2021 (estimated)
  3. Primary completionDec 2023 (estimated)
  4. Study completionDec 2024 (estimated)

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
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
120 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05107037
Sponsor's protocol ID
TQ-B3234-I-02
Status last verified
Jun 2021
First submitted
3 Sep 2021
Last updated
4 Nov 2021
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing TQ-B3234 capsule in people with Type I Neurofibromatosis, 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 24 inclusion and 32 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: status not confirmed, as of the sponsor's last update on 4 Nov 2021. 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 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.

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

Are results available for this study?

Results are not available in the source record.

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

Contact Qingfeng Li, Doctor (021-2327169, dr.liqingfeng@shsmu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum tolerated dose (MTD) (time frame: Baseline up to 48weeks). The study lists 4 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 NCT05107037.

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 4 Nov 2021.

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