Precision Medicine Trial Based on Molecular Matching Therapy for Patients With Standard Treatment Exhaustion

Официальное название

A Pan-Cancer Basket, Real World, Open-label, Multicenter Study on Molecular Matching Therapy Guided by Molecular Tumor Boards (MTB) for Pan Solid Tumor Patients With Standard Treatment Exhaustion

Обзор

The main purpose of this study is to explore the feasibility of selecting treatment plans based on genomic variations guided by MTB in patients with advanced refractory solid tumors.

Подробное описание

Using comprehensive genome sequencing to analyze recurrent and metastatic solid tumors that have failed previous conventional treatments, and matching possible targeted therapy drugs to screen for potential effective treatment drugs until tumor disease progression, and then continuing to monitor tumor resistance mutation signals and provide matching therapy, can help improve the clinical outcomes of patients with advanced refractory tumors, and is also an important direction for personalized and precise treatment of tumors in the future. Therefore, the investigators designed this study to explore the feasibility, effectiveness, and safety of targeted therapy based on tumor molecular feature matching for advanced solid tumor patients who have failed previous treatments. All patients who receive treatment with a drug available in the protocol will be followed for standard efficacy outcomes including clinical efficacy ,clinical safety and exploratory endpoints such as biomarkers for drug response, change in the tumor microenvironment. The core concepts of the clinical research interventional initiated include: target priority principle, combination therapy principle, individualized dose adjustment method for combination therapy, and Bayesian adaptive trial design. For some clinical studies, to meet the primary objective, at least 35% of participants had to achieve a PFS2(Progression-Free Survival 2)/PFS1(Progression-Free Survival 1) ≥ 1.3 in a sample population of 25 evaluable patients. Sample size was calculated using an exact single-stage design for phase II studies with a one-sided type I error of 5% and a power of 90% under the assumption that PFS2/PFS1≥ 1.3 in ≤10% of patients would be clinically irrelevant, while a success rate ≥ 35% would merit further investigation.

Вмешательства

• Препарат Olaparib tablet
  Usage and dosage: The recommended dosage is 200mg, twice a day, equivalent to a total daily dose of 400mg.The dosage for combined use will be adaptively adjusted by the researcher.Essentially, for de novo combinations, we started patients at about 50% of the usual dose of each drug for two-drug combinations, and at about one-third of the dose of each drug for three-drug combinations. Patients then received escalating doses of drugs to tolerance, while being monitored closely by their treating ph
• Препарат Temozolomide capsule
  Administration method and dosage: 75mg/m2, orally administered for 7 consecutive days, with a treatment cycle of every 21 days.The dosage for combined use will be adaptively adjusted by the researcher.Essentially, for de novo combinations, we started patients at about 50% of the usual dose of each drug for two-drug combinations, and at about one-third of the dose of each drug for three-drug combinations. Patients then received escalating doses of drugs to tolerance, while being monitored closely
• Препарат Anlotinib
  Usage, dosage, and administration method: Take orally once a day before breakfast. Take the medication continuously for 2 weeks and stop taking it for 1 week, that is, 3 weeks (21 days) is one course of treatment. Until disease progression or intolerable toxic side effects occur.The dosage for combined use will be adaptively adjusted by the researcher.Essentially, for de novo combinations, we started patients at about 50% of the usual dose of each drug for two-drug combinations, and at about one
• Препарат Trametinib tablet
  Usage, dosage, and administration method: The recommended dose is 2 mg, taken orally once a day with an interval of approximately 24 hours. The dose should be taken at least 1 hour before meals or 2 hours after meals. Do not take any missed doses of trametinib within 12 hours of taking the next dose.The dosage for combined use will be adaptively adjusted by the researcher.Essentially, for de novo combinations, we started patients at about 50% of the usual dose of each drug for two-drug combinati
• Препарат Dabrafenib
  Usage and dosage: Take 150mg orally twice a day, with an interval of about 12 hours.Essentially, for de novo combinations, we started patients at about 50% of the usual dose of each drug for two-drug combinations, and at about one-third of the dose of each drug for three-drug combinations. Patients then received escalating doses of drugs to tolerance, while being monitored closely by their treating physicians. Combinations of drugs with overlapping toxicities were avoided. When this product is u
• Препарат Vebreltinib Enteric Capsules
  Usage and dosage: The recommended starting dose is 200 mg/time, taken orally twice a day (once in the morning and once in the evening), until disease progression or intolerable toxicity occurs.The dosage for combined use will be adaptively adjusted by the researcher.Essentially, for de novo combinations, we started patients at about 50% of the usual dose of each drug for two-drug combinations, and at about one-third of the dose of each drug for three-drug combinations. Patients then received esc
• Препарат Alpelisib Pill
  Usage and dosage: The recommended dosage is 300mg (two 150mg film tablets), taken once a day with food; Continue treatment until the disease worsens or unacceptable toxicity occurs.Administration method: Patients should take aspirin at approximately the same time every day and swallow the entire aspirin tablet (the tablet should not be chewed, crushed, or separated before swallowing).The dosage for combined use will be adaptively adjusted by the researcher.Essentially, for de novo combinations,
• Препарат Sacituzumab Govitecan-Hziy 180 MG
  Usage and dosage: The recommended dosage is 10 mg/kg, administered intravenously every 21 days as a treatment cycle on the 1st and 8th days, and continued until disease progression or unacceptable toxicity occurs. The dosage of this product should not exceed 10 mg/kg.The dosage for combined use will be adaptively adjusted by the researcher.Essentially, for de novo combinations, we started patients at about 50% of the usual dose of each drug for two-drug combinations, and at about one-third of th
• Препарат Lenvatinib Capsules
  Usage and dosage: For patients weighing less than 60kg, the recommended daily dose of lenvatinib is 8mg once a day; For patients weighing ≥ 60kg, the recommended daily dose of lenvatinib is 12mg once daily. Lunvatinib should be taken at a fixed time every day, on an empty stomach or with food.The dosage for combined use will be adaptively adjusted by the researcher.Essentially, for de novo combinations, we started patients at about 50% of the usual dose of each drug for two-drug combinations, an
• Препарат Pazopanib Pill
  Usage and dosage: In the safety introduction section, the initial dose of pazopanib is 400mg, and in the dose escalation queue, the dose of pazopanib is 600mg.The dosage for combined use will be adaptively adjusted by the researcher. Administration method: Oral treatment once a day, with a cycle of 28 days.Essentially, for de novo combinations, we started patients at about 50% of the usual dose of each drug for two-drug combinations, and at about one-third of the dose of each drug for three-dru

Первичные конечные точки

• PFS2/PFS1(Progression Free Survival 2/Progression Free Survival 1) [Срок оценки: 24 months]

Вторичные конечные точки (3)

• OS(Overall Survival) [Срок оценки: 24 months]
• ORR(Objective Response Rate) [Срок оценки: 24 months]
• Number of treatment related adverse events with grade 3 or greater severity by CTCAE 5.0 [Срок оценки: 24 months]

Критерии участия

Критерии включения

• Recurrent or metastatic malignant solid tumors diagnosed by histology or cytology;
• ECOG score 0-4 (3-4 points only for patients with tumor burden);
• Those who fail or cannot tolerate standard treatment, or those who refuse standard treatment;
• At least one measurable lesion that meets the RECIST 1.1 standard;
• Expected survival period ≥ 3 months;
• Age ≥ 18 years old;
• Tumor tissue blocks with sufficient formalin fixed paraffin embedding (FFPE), or chest or ascites with cancer cells detected during treatment (not less than 200ml), or excised metastatic lymph nodes, or peripheral blood (approximately 5m1) can be used for genetic testing;
• Understand and voluntarily participate in this study, and sign the informed consent form.

Критерии исключения

• Patients who have actively undergone or are currently participating in clinical trials for treatment;
• Serious or uncontrolled medical diseases (i.e. uncontrolled diabetes, chronic kidney disease, chronic lung disease or uncontrolled active infection, mental diseases/social conditions that limit the compliance with the research requirements) that the researchers think will confuse the research treatment response analysis;
• Pregnant or lactating patients, or any patients with fertility, have not taken appropriate pregnancy prevention measures.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Tianjin Medical Unversity Second Hospital — Тяньцзинь

Идентификаторы

NCT: NCT06739395 · MyCustom-02

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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