Cryoablation in Combination (or Not) With Pembrolizumab and Pemetrexed-carboplatin in 1st-line Treatment for Patients With Metastatic Lung Adenocarcinoma

Официальное название

Cryoablation in Combination (or Not) With Pembrolizumab and Pemetrexed-carboplatin in First-line Treatment for Patients With Metastatic Lung Adenocarcinoma: A Randomized Phase III Study

Обзор

This study aims to compare the one-year survival benefit of the association of cryoablation-pembrolizumab-pemetrexed-carboplatin versus pembrolizumab-pemetrexed-carboplatin in metastatic lung adenocarcinoma patients. This is a multicenter, prospective, open-labeled, 2-arm comparative randomized (1:1) phase III trial. Patients will be randomized with a 1:1 ratio into: * Arm A (experimental arm): cryoablation of one visceral lesion or bone metastasis excluding liver and sclerotic bone metastases combined with pembrolizumab and pemetrexed-carboplatin prescribed as per market authorization. * Arm B (standard arm): pembrolizumab and pemetrexed-carboplatin prescribed as per market authorization. Pembrolizumab and pemetrexed-carboplatin will be prescribed and administered at the dose recommended by market authorization. Cryoablation treatment should be performed within 6 weeks after the first administration of pembrolizumab. No treatment switching permitted.

Подробное описание

Upon signature of the informed consent and verification of the screening results, eligible participants will be randomized between two therapeutic strategies:

* Arm A (experimental arm): cryoablation of visceral lesion or bone metastasis excluding liver and sclerotic bone metastases combined with pembrolizumab and pemetrexed-carboplatin prescribed as per market authorization. * Arm B (standard arm): pembrolizumab and pemetrexed-carboplatin prescribed as per market authorization.

Pembrolizumab treatment should begin no later than 7 days after randomization. The cryoablation treatment should be performed within 6 weeks after the first administration of pembrolizumab.

RECIST v1.1 tumour assessment:Tumour response will be defined and assessed as per the Response Evaluation Criteria in Solid Tumors (RECIST v1.1).

* A comprehensive workup will be performed at baseline and every 9 weeks. * The same method will be used to evaluate each identified lesion both at baseline and throughout the study. * Treatment will be administered as long as no disease progression or unacceptable toxicity is found, or as long as no other reasons for treatment discontinuation are met. * Assessment of efficacy will be essentially based on a set of measurable lesions identified at baseline as target lesions and followed until disease progression and following the RECIST v1.1 criteria. * Confirmation of response at least 4 weeks later is not required in this randomized study where response is not the primary endpoint.

SAFETY :Patients will be evaluable for safety if they have received at least one treatment administration. Safety profile will be continuously followed during treatment up to 90 days after the last immunotherapy treatment administration or until the start of a new antitumor therapy or until 12 months of treatment, whichever occurs first.

STUDY PROCEDURES :

Blood sample will be collected at baseline (Day 1: before treatment initiation), Day 1 cycle 2 (Day 21 +/- 3 days), Day 1 cycle 3 (Day 42 +/- 3 days) and progression.

Patients will be asked to provide samples of biopsy tissue at screening (prior to anticancer agent with immunomodulatory activity treatment initiation), during treatment (day 42 +/- 3 days) and at disease progression as follows. Tumor biopsy at inclusion is optional if materiel archived fixed in formalin and embedded in paraffin of diagnostic biopsy is available.

All randomized patients will be followed up until death or the end of the follow-up period, defined as 36 months after randomization, whichever occurs first. For all patients, treatments regimen, tumor response during and/or after treatment, survival follow-up will be collected on study database:

* Every 3 months until loco-regional relapse or metastasis evidence, death or until the date of study termination, whichever occurs first, * Every 6 months after loco-regional relapse or metastasis evidence, until death or until the date of study termination, whichever occurs first.

Вмешательства

• Устройство Cryoablation
  Cryoablation will be performed by a specialized radiologist, percutaneously, ie "through the skin". The operation is performed under general anesthesia, under the guidance of the scanner. The images from the scanner make it possible to precisely insert and place a needle at the level of the tumor to be treated. Intense cold will be produced by the needle and will destroy the cancer cells by freezing (temperatures of -40 °C). Freezing is localized to the tumor, the rest of the organ will not suff
• Препарат Pembrolizumab
  Pembrolizumab will be prescribed and administered at the dose recommended by market authorization.
• Препарат Pemetrexed
  Pemetrexed will be prescribed and administered at the dose recommended by market authorization.
• Препарат Carboplatin
  Carboplatin will be prescribed and administered at the dose recommended by market authorization.

Первичные конечные точки

• 1-year overall survival rate [Срок оценки: 1 year]

Вторичные конечные точки (12)

• Overall response rate within 6 months as per RECIST v1.1 [Срок оценки: throughout the treatment period, an expected average of 6 months]
• Overall response rate at 6 months as per RECIST v1.1 [Срок оценки: 6 months]
• Overall response rate as per RECIST v1.1 [Срок оценки: throughout the treatment period, an expected average of 1 year]
• Duration of overall response [Срок оценки: throughout the treatment period, an expected average of 1 year]
• Best overall response rate as per RECIST v1.1 [Срок оценки: throughout the treatment period, an expected average of 1 year]
• 2-year overall survival rate [Срок оценки: 2 years]
• 1-year progression-free survival rate [Срок оценки: 1 year]
• 2-year progression-free survival rate [Срок оценки: 2 years]
• Mean scores of each dimension of QLQ-C30 from EORTC quality of life group [Срок оценки: at baseline, 3, 6, 9, 12 and 24 months]
• Time to health-related quality of life score definitive deterioration (targeted dimension of EORTC QLQC30 : global health) [Срок оценки: at baseline, 3, 6, 9, 12 and 24 months]
• Number of patient receiving a post-progression treatment [Срок оценки: an average of 6 months]
• Overall response rate as per iRECIST [Срок оценки: throughout the treatment period, an expected average of 6 months]

Критерии участия

Критерии включения

• Histologically or cytologically confirmed non-small lung adenocarcinoma.
• Metastatic disease.
• Treatment with pembrolizumab in combination with pemetrexed-carboplatin as per market authorization.
• At least two target lesions (RECIST1.1), measurable with CT or MRI :

• One target lesion that is amenable for accurate repeated measurements,
• One target lesion (15-40 mm) that is amenable for cryoablation treatment including lung, kidney, adrenal, soft tissue and lytic bone lesions. Liver and sclerotic bone lesions are not allowed to be treated by cryoablation.
• Age ≥ 18.
• Performance status ≤ 2.
• Women of childbearing potential must have a negative serum pregnancy test prior to registration.
• Recovery to grade ≤ 1 from any adverse event derived from previous treatment (excluding alopecia)
• Patients with a social security in compliance with the French law (Loi Jardé).
• Patients must be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.
• Voluntarily signed and dated written informed consents prior to any study specific procedure.

Критерии исключения

• Squamous cell tumors and other than adenocarcinoma.
• Prior systemic treatment for advanced non-small cell lung cancer (except adjuvant therapy after complete resection).
• Current or prior use of immunosuppressive medication including any use of oral glucocorticoids, within 21 days before the first dose of pembrolizumab.
• Known contra-indication and/or hypersensitivity to PD1/PD-L1 antagonist and/or cytotoxic therapy.
• Known contra-indication to cryoablation.
• Abnormal coagulation contraindicating biopsy.
• Prior or concurrent malignant disease diagnosed or treated in the last 2 years except for adequately treated in situ carcinoma of the cervix, basal or squamous skin cell carcinoma or incidentally discovered good prognosis prostate cancer (T stage < pT3 and Gleason ≤ 7).
• Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy.
• Subjects who participated in an investigational drug or device study within 28 days prior to study entry.
• Known infection with HIV, hepatitis B, or hepatitis C.
• Females who are pregnant or breast-feeding.
• Men or women refusing contraception.
• Concomitant disease or condition that could interfere with the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the subject in this study.
• Previous enrolment in the present study.
• Individuals deprived of liberty or placed under legal guardianship.

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

Лечение

Центры проведения

Франция · 1 центр

• Institut Bergonié — Bordeaux

Идентификаторы

NCT: NCT04339218 · IB 2019-05 · 2019-A02477-50

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗