Theranostic Approach by Early Multigene Sequencing in Advanced Poor Prognosis Cancers

Официальное название

Theranostic Approach by Early Multigene Sequencing in Advanced Poor Prognosis Cancers, Not Eligible for Initial Sequencing in Clinical Routine and Selected From the First Line in Molecular Tumour Board.

Обзор

The European Society for Medical Oncology (ESMO) strongly recommends to develop multigene sequencing in the framework of molecular screening programmes, in order to improve access to innovative drugs and to accelerate clinical research in cancers. * Accordingly, this project aims to study the contribution of early systematic multigene sequencing (NGS) discussed in Molecular Tumour Board for poor prognosis cancers, with no current indication for early sequencing. * The investigators teams propose to perform a randomized study in tumours in which actionable therapeutic targets according to the ESMO ESCAT scale are known (ESCAT II/IV) especially in pancreatic ductal adenocarcinoma, hepatocellular carcinoma or triple negative breast cancer. Two approaches will be compared: a large multigenic early sequencing approach since the first line setting versus a Plan France Medecine Genomique 2025 approach since the second line setting. The frequency of really initiated therapeutic proposals according to the molecular status will be compared in each group.

Подробное описание

Part 1 sequential multi-gene sequencing (Simple NGS),

* Multi-gene DNA sequencing (43 genes panel corresponding to the most frequently targeted molecular alterations) * And if no contributive:

Part 2: randomized study between two sequential approaches

\- Experimental arm: early Multi-gene DNA sequencing (638 genes panel) Multi-gene RNA sequencing (ARCHER panel)

1. MMR status in molecular biology 2. \- Tumour Mutational Burden

* Control arm: after 1st line escape, according to Plan France Medecine Genomique 2025 In the Part 2, a new biopsy could be proposed if necessary

Вмешательства

• Генная терапия Large and early multigene sequencing
  Part 1 sequential multi-gene sequencing (Simple NGS), * Multi-gene DNA sequencing (43 genes panel corresponding to the most frequently targeted molecular alterations) * And if no contributive: Part 2: randomized study between two sequential approaches \- Experimental arm: early Multi-gene DNA sequencing (638 genes panel) Multi-gene RNA sequencing (ARCHER panel) 1. MMR status in molecular biology 2. \- Tumour Mutational Burden * Control arm: after 1st line escape, according to Plan France

Первичные конечные точки

• Frequency of patients receiving a proposal for treatment leading to effective initiation of treatment. [Срок оценки: Within 2 years of the first Molecular Tumour Board.]

Вторичные конечные точки (5)

• 1. Frequency of therapeutic proposals, whether or not leading to treatment, among patients with at least one molecular alteration found [Срок оценки: Within 2 years of the first Molecular Tumour Board.]
• 2. The number of potentially targetable molecular alterations found. [Срок оценки: Within 2 years of the first Molecular Tumour Board.]
• The frequency of the types of potentially targetable molecular alterations found according to the ESCAT classification (ESCAT I / II / III / IV). [Срок оценки: Within 2 years of the first Molecular Tumour Board.]
• 4. Frequency of types of therapeutic proposals (clinical trials, off-label targeted therapies). [Срок оценки: Within 2 years of the first Molecular Tumour Board.]
• Time to treatment proposal, defined as the time between the date of the first Molecular Tumour Board and the treatment proposal following the second Molecular Tumour Board. [Срок оценки: Within 2 years of the first Molecular Tumour Board.]

Критерии участия

Критерии включения

• \- Age >18 years.
• Advanced disease status ("unresectable" or "metastatic").
• Patient included either at the time of diagnostic investigation or during first line of treatment.
• Good general conditions, still compatible with a therapeutic proposal, WHO 0-1.
• The following tumour sites, with poor prognosis and for which ESCAT II/IV treatment targets can be found according to ESMO:

• pancreatic adenocarcinoma
• hepatocellular carcinomas,
• triple negative breast cancer.
• Tumour tissue a priori available in sufficient quantity: at least one biopsy from a visceral metastatic site or surgical specimen (if available) for eligible cancers.
• Patient covered by a social sercurity scheme

Критерии исключения

• \- General condition WHO >1 and/or nutritional status not compatible with a therapeutic proposal
• Limiting systemic cardiovascular, renal, bronchopulmonary or endocrinological comorbidities with the initiation of a therapeutic proposal
• Active infection or active chronic disease (diabetes, liver dysfunction, immune disease) making the patient's condition incompatible with a therapeutic proposal.
• A priori unavailable, in insufficient quantity or of suboptimal quality tumour material.
• Administrative reasons: inability to receive informed information, inability to participate in the entire study, lack of social security coverage, refusal to sign consent.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Скрининг

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT06958224 · 2023_0285

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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