Lung AdenocarcinomaPhase 3CRYOMUNENCT04339218
Cryoablation in Combination (or Not) With Pembrolizumab and Pemetrexed-carboplatin in 1st-line Treatment for Patients With Metastatic Lung Adenocarcinoma
A Phase 3 study testing Cryoablation, Pembrolizumab and Pemetrexed in people with Lung Adenocarcinoma and Cryotherapy Effect, run by Institut Bergonié at 1 site in France.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lung Adenocarcinoma, Cryotherapy Effect
- What is being tested?
- Cryoablation, Pembrolizumab and Pemetrexed
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 214 participants
- Where
- 1 siteFrance
- Study dates
- 28 Aug 2020to 27 Aug 2028
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Simone MATHOULIN-PELISSIER, MD, PhD contact
France1 site, 1 recruiting
- Recruiting
Institut Bergonié
Bordeaux, Gironde, 33076
Jean PALUSSIERE, MD, 0556333347, j.palussiere@bordeaux.unicancer.fr
Antoine ITALIANO, MD, PhD, a.italiano@bordeaux.unicancer.fr
About this study
Official title: 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
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.
Read more
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.
Read the detailed description
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.
- Conditions
- Lung Adenocarcinoma, Cryotherapy Effect
- Being tested
- Cryoablation, Pembrolizumab, Pemetrexed, Carboplatin
- Keywords
- Lung adenocarcinoma, immunotherapy, cryoablation
- Medical subject headings
- Adenocarcinoma of Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CryoablationDevice
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 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.
PembrolizumabDrug
Pembrolizumab will be prescribed and administered at the dose recommended by market authorization.
PemetrexedDrug
Pemetrexed will be prescribed and administered at the dose recommended by market authorization.
CarboplatinDrug
Carboplatin will be prescribed and administered at the dose recommended by market authorization.
| Study group | Role | What they receive |
|---|---|---|
| Arm Cryoablation+pembrolizumab-pemetrexed-carboplatin | Experimental | 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. Receives: Device: Cryoablation; Drug: Pembrolizumab; Drug: Pemetrexed; Drug: Carboplatin |
| Arm pembrolizumab-pemetrexed-carboplatin | Active comparator | Combination of Pembrolizumab and pemetrexed-carboplatin prescribed as per market authorization. Receives: Drug: Pembrolizumab; Drug: Pemetrexed; Drug: Carboplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 1 year
Secondary outcomes (26)
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.
Measured: throughout the treatment period, an expected average of 6 months
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.
Measured: 6 months
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.
Measured: throughout the treatment period, an expected average of 1 year
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.
Measured: throughout the treatment period, an expected average of 1 year
Best overall response rate as per RECIST v1.1
Best overall response rate (BoR) is defined as rate of patients with the best response across all time points (RECIST v1.1). The best overall response will be determined once all the data for the patient is known.
Measured: throughout the treatment period, an expected average of 1 year
2-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). 2-year OS rates will be compared between arms.
Measured: 2 years
1-year progression-free survival rate
Progression-free survival (PFS) is defined as the time interval between the date of randomization and the date of progression (RECIST v1.1) or death (from any cause), whichever occurs first.The analysis of PFS will be based on the censoring process following FDA guidelines. Progression is defined using RECIST v1.1, as a 20% increase in the sum of diameters of target lesions (taking as reference the smallest sum on study), or a unequivocal progression of existing non-target lesions, or the appearance of one or more new lesions.1-year PFS rates will be compared between arms.
Measured: 1 year
2-year progression-free survival rate
Progression-free survival (PFS) is defined as the time interval between the date of randomization and the date of progression (RECIST v1.1) or death (from any cause), whichever occurs first.The analysis of PFS will be based on the censoring process following FDA guidelines. Progression is defined using RECIST v1.1, as a 20% increase in the sum of diameters of target lesions (taking as reference the smallest sum on study), or a unequivocal progression of existing non-target lesions, or the appearance of one or more new lesions.2-year PFS rates will be compared between arms.
Measured: 2 years
Mean scores of each dimension of QLQ-C30 from EORTC quality of life group
Health-related quality of life (HRQoL) will be assessed through EORTC QLQ-C30 (Aaronson et al. J Natl Cancer Inst 1993).The QLQ-C30 is a questionnaire developed to assess the quality of life of cancer patients. The questionnaire includes one global health status/QoL scale, five functional scales and three symptom scale. Each scale is scored from 0 to 100. A high score on a scale indicate a good outcome for the dimension of QoL.
Measured: 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)
Time until definitive deterioration (TUDD) of HRQoL is defined as the time from the date of randomization to a first deterioration of at least 10 points of HRQoL as compared to the baseline score (Bonnetain et al. Eur J Cancer 2010).
Measured: at baseline, 3, 6, 9, 12 and 24 months
Number of patient receiving a post-progression treatment
Post-progression treatment is defined as the treatment (systemic/local) given after the first progression under cryoablation+pembrolizumab and pemetrexed-carboplatin or pembrolizumab and pemetrexed-carboplatin.
Measured: an average of 6 months
Overall response rate as per iRECIST
Overall response rate (ORR) is defined as the rate of patients with immune complete or partial responses (iCR, iPR) as per iRECIST (Seymour et al. 2017). iCR and iPR can be assigned after iUPD (immune unconfirmed progressive disease) has been documented.
Measured: throughout the treatment period, an expected average of 6 months
Duration of immune overall response
Duration of i-response (iDoR) is defined as the time from the date of the first response iCR/iPR (whichever is first recorded) to the date of PD (iUPD confirmed as iCPD). iDOR is only defined for subjects who have best overall response of iCR or iPR.
Measured: throughout the treatment period, an expected average of 1 year
1-year immune-progression-free survival rate
Immune-progression-free survival (iPFS) is defined as the time interval between the date of randomization and the date of progression (iRECIST) or death (from any cause), whichever occurs first. The event date to be used for calculation of progression-free survival (iPFS) should be the first date at which progression criteria are met (ie, the date of iUPD) provided that iCPD is confirmed at the next assessment. 1-year iPFS rates will be compared between arms.
Measured: 1 year
2-year immune-progression-free survival rate
Immune-progression-free survival (iPFS) is defined as the time interval between the date of randomization and the date of progression (iRECIST) or death (from any cause), whichever occurs first. The event date to be used for calculation of progression-free survival (iPFS) should be the first date at which progression criteria are met (ie, the date of iUPD) provided that iCPD is confirmed at the next assessment. 2-year iPFS rates will be compared between arms.
Measured: 2 year
Best overall response rate as per iRECIST
Best overall response rate (iBoR) is defined, according to iRECIST, as the rate of patients with the best timepoint response recorded from the start of the study treatment until the end of treatment, taking into account any requirement for confirmation.
Measured: throughout the treatment period, an expected average of 1 year
Number of immune-related SAEs (CTCAE NCI V5)
Serious Adverse events (SAEs) will be coded and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) NCI v5.
Measured: throughout the treatment period, an expected average of 1 year
Number of immune-related AEs (CTCAE NCI V5)
Adverse events (AEs) will be coded and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) NCI v5.
Measured: throughout the treatment period, an expected average of 1 year
Number of chemotherapy-related SAEs (CTCAE NCI V5)
Serious Adverse events (SAEs) will be coded and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) NCI v5.
Measured: throughout the treatment period, an expected average of 1 year
Number of chemotherapy-related AEs (CTCAE NCI V5)
Adverse events (AEs) will be coded and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) NCI v5.
Measured: throughout the treatment period, an expected average of 1 year
Number of cryoablation-related SAEs (CTCAE NCI V5)
Serious Adverse events (SAEs) will be coded and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) NCI v5.
Measured: throughout the treatment period, an expected average of 1 year
Number of cryoablation-related AEs (CTCAE NCI V5)
Adverse events (AEs) will be coded and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) NCI v5.
Measured: throughout the treatment period, an expected average of 1 year
Number of SAEs related to study procedures (CTCAE NCI V5)
Serious Adverse events (SAEs) will be coded and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) NCI v5.
Measured: throughout the treatment period, an expected average of 1 year
Number of AEs related to study procedures (CTCAE NCI V5)
Adverse events (AEs) will be coded and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) NCI v5.
Measured: throughout the treatment period, an expected average of 1 year
Number of hospitalisations in experimental arm only
counts of hospitalisations within 30 days after the cryoablation will be summarized by treatment strategy.
Measured: within 6 weeks + 30 days after first pembrolizumab administration
Percentage of patients that worsen their ECOG score of 1 or more point
Percentage of patients that worsen their ECOG score of 1 or more point at follow-up visits post randomization will be summarized by treatment strategy.
Measured: at follow-up visits post randomization (an average of 2 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Apr 2020
- Study start28 Aug 2020
- Primary completion27 Aug 2026 (estimated)
- Study completion27 Aug 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lung AdenocarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 214 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Institut Bergonié
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jean PALUSSIERE, MD, Principal investigator, Institut Bergonié
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04339218
- Sponsor's protocol ID
- IB 2019-05
- Other IDs
- 2019-A02477-50
- Acronym
- CRYOMUNE
- Status last verified
- Jan 2026
- First submitted
- 6 Apr 2020
- Last updated
- 30 Jan 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04339218
- Acronym / sponsor ID
- CRYOMUNE / IB 2019-05
- Conditions
- Lung Adenocarcinoma, Cryotherapy Effect
- Keywords
- Lung adenocarcinoma, immunotherapy, cryoablation
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 214 participants (estimated)
- Lead sponsor
- Institut BergoniéUniversity, hospital or other
- Study start
- 28 Aug 2020 (actual)
- Primary completion
- 27 Aug 2026 (estimated)
- Study completion
- 27 Aug 2028 (estimated)
- First posted
- 9 Apr 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm Cryoablation+pembrolizumab-pemetrexed-carboplatin | Experimental | Device: Cryoablation, Drug: Pembrolizumab, Drug: Pemetrexed, Drug: CarboplatinCryoablation 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 pembrolizumab-pemetrexed-carboplatin | Active comparator | Drug: Pembrolizumab, Drug: Pemetrexed, Drug: CarboplatinCombination of Pembrolizumab and pemetrexed-carboplatin prescribed as per market authorization. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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 :
- Age ≥ 18.
Key exclusion criteria (15 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CryoablationCryoablation 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. | Device | Arm Cryoablation+pembrolizumab-pemetrexed-carboplatin |
| PembrolizumabPembrolizumab will be prescribed and administered at the dose recommended by market authorization. | Drug | Arm Cryoablation+pembrolizumab-pemetrexed-carboplatin, Arm pembrolizumab-pemetrexed-carboplatin |
| PemetrexedPemetrexed will be prescribed and administered at the dose recommended by market authorization. | Drug | Arm Cryoablation+pembrolizumab-pemetrexed-carboplatin, Arm pembrolizumab-pemetrexed-carboplatin |
| CarboplatinCarboplatin will be prescribed and administered at the dose recommended by market authorization. | Drug | Arm Cryoablation+pembrolizumab-pemetrexed-carboplatin, Arm pembrolizumab-pemetrexed-carboplatin |
Primary outcome
1-year overall survival rate
Time frame: 1 year
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.
26 secondary outcomes
Overall response rate within 6 months as per RECIST v1.1
Time frame: throughout the treatment period, an expected average of 6 months
Overall response rate at 6 months as per RECIST v1.1
Time frame: 6 months
Overall response rate as per RECIST v1.1
Time frame: throughout the treatment period, an expected average of 1 year
Duration of overall response
Time frame: throughout the treatment period, an expected average of 1 year
Best overall response rate as per RECIST v1.1
Time frame: throughout the treatment period, an expected average of 1 year
2-year overall survival rate
Time frame: 2 years
1-year progression-free survival rate
Time frame: 1 year
2-year progression-free survival rate
Time frame: 2 years
Mean scores of each dimension of QLQ-C30 from EORTC quality of life group
Time frame: 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)
Time frame: at baseline, 3, 6, 9, 12 and 24 months
Number of patient receiving a post-progression treatment
Time frame: an average of 6 months
Overall response rate as per iRECIST
Time frame: throughout the treatment period, an expected average of 6 months
Duration of immune overall response
Time frame: throughout the treatment period, an expected average of 1 year
1-year immune-progression-free survival rate
Time frame: 1 year
2-year immune-progression-free survival rate
Time frame: 2 year
Best overall response rate as per iRECIST
Time frame: throughout the treatment period, an expected average of 1 year
Number of immune-related SAEs (CTCAE NCI V5)
Time frame: throughout the treatment period, an expected average of 1 year
Number of immune-related AEs (CTCAE NCI V5)
Time frame: throughout the treatment period, an expected average of 1 year
Number of chemotherapy-related SAEs (CTCAE NCI V5)
Time frame: throughout the treatment period, an expected average of 1 year
Number of chemotherapy-related AEs (CTCAE NCI V5)
Time frame: throughout the treatment period, an expected average of 1 year
Number of cryoablation-related SAEs (CTCAE NCI V5)
Time frame: throughout the treatment period, an expected average of 1 year
Number of cryoablation-related AEs (CTCAE NCI V5)
Time frame: throughout the treatment period, an expected average of 1 year
Number of SAEs related to study procedures (CTCAE NCI V5)
Time frame: throughout the treatment period, an expected average of 1 year
Number of AEs related to study procedures (CTCAE NCI V5)
Time frame: throughout the treatment period, an expected average of 1 year
Number of hospitalisations in experimental arm only
Time frame: within 6 weeks + 30 days after first pembrolizumab administration
Percentage of patients that worsen their ECOG score of 1 or more point
Time frame: at follow-up visits post randomization (an average of 2 years)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Simone MATHOULIN-PELISSIER, MD, PhD contact
Jean PALUSSIERE, MD principal investigator
Institut Bergonié
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Cryoablation, Pembrolizumab and Pemetrexed in people with Lung Adenocarcinoma and Cryotherapy Effect, run by Institut Bergonié at 1 site in France.
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 13 inclusion and 15 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: looking for participants now, as of the sponsor's last update on 30 Jan 2026. 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 France. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jean PALUSSIERE, MD (05.56.33.33.47 ext. +33, j.palussiere@bordeaux.unicancer.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
1-year overall survival rate (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 30 Jan 2026.