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.
Histologically or cytologically confirmed non-small lung adenocarcinoma.
Metastatic disease.
Treatment with pembrolizumab in combination with pemetrexed-carboplatin as per market authorization.
One target lesion that is amenable for accurate repeated measurements,
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.
Parallel
Cryoablation
DeviceCryoablation 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 suffer from the cold. The aftermath of the intervention causes only minimal pain and in most cases does not require pain treatment. As the operation is minimally traumatic, the risk of complications is low. Hospitalization is around twenty-four hours and usual or professional activities can be resumed very quickly.
Pembrolizumab
DrugPembrolizumab will be prescribed and administered at the dose recommended by market authorization.
Pemetrexed
DrugPemetrexed will be prescribed and administered at the dose recommended by market authorization.
Carboplatin
DrugCarboplatin will be prescribed and administered at the dose recommended by market authorization.
1-year overall survival rate
Overall survival (OS) is defined as the time interval between the date of randomization and the date of death (from any cause). Patients alive will be censored at the date of last follow-up or last patient contact. One-year OS rates will be compared between arms.
Overall response rate within 6 months as per RECIST v1.1
Overall response rate (ORR) is defined as the rate of patients with complete or partial response (CR, PR) as per RECIST v1.1. According to RECIST v1.1: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.; Overall Response (OR) = CR + PR.
Overall response rate at 6 months as per RECIST v1.1
Overall response rate (ORR) is defined as the rate of patients with complete or partial response (CR, PR) as per RECIST v1.1. According to RECIST v1.1: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.; Overall Response (OR) = CR + PR.
Overall response rate as per RECIST v1.1
Overall response rate (ORR) is defined as the rate of patients with complete or partial response (CR, PR) as per RECIST v1.1. ORR will be assessed across all time points, once all the data for the patient is known. According to RECIST v1.1: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.; Overall Response (OR) = CR + PR.
Duration of overall response
The duration of overall response (DoR) is defined as the time from documentation of tumour response (Complete or partial responses whichever is first recorded) to disease progression, according to RECIST v1.1. Kaplan-Meier Method will be used to estimate DoR.
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