Combining cryoablation with immunotherapy for lung cancer treatment

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 is testing if adding cryoablation to standard lung cancer treatment can help people with metastatic lung adenocarcinoma live longer.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 214 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Institut Bergonié (other)
• Drugs / interventions: pembrolizumab, immunotherapy
• Locations: 1 site (Bordeaux, Gironde)
• Trial ID: NCT04339218 on ClinicalTrials.gov

What this trial studies

This clinical trial compares the one-year survival benefit of combining cryoablation with pembrolizumab and pemetrexed-carboplatin against the standard treatment of pembrolizumab and pemetrexed-carboplatin alone in patients with metastatic lung adenocarcinoma. Participants will be randomly assigned to one of two arms: the experimental arm receiving cryoablation alongside the standard treatment, or the control arm receiving only the standard treatment. The study will assess tumor response using RECIST v1.1 criteria and will monitor participants for disease progression and treatment toxicity. The trial aims to determine if the addition of cryoablation improves survival outcomes for these patients.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with histologically confirmed metastatic lung adenocarcinoma and specific measurable lesions suitable for cryoablation.

Not a fit: Patients with liver or sclerotic bone metastases, or those who do not meet the eligibility criteria, may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly improve survival rates for patients with metastatic lung adenocarcinoma.

How similar studies have performed: While the combination of immunotherapy and chemotherapy has been explored, the specific use of cryoablation in this context is relatively novel and has not been extensively tested in prior studies.

Eligibility criteria

Inclusion Criteria:

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

   1. One target lesion that is amenable for accurate repeated measurements,
   2. 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.
5. Age ≥ 18.
6. Performance status ≤ 2.
7. Women of childbearing potential must have a negative serum pregnancy test prior to registration.
8. Recovery to grade ≤ 1 from any adverse event derived from previous treatment (excluding alopecia)
9. Patients with a social security in compliance with the French law (Loi Jardé).
10. Patients must be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.
11. Voluntarily signed and dated written informed consents prior to any study specific procedure.

Exclusion Criteria:

1. Squamous cell tumors and other than adenocarcinoma.
2. Prior systemic treatment for advanced non-small cell lung cancer (except adjuvant therapy after complete resection).
3. Current or prior use of immunosuppressive medication including any use of oral glucocorticoids, within 21 days before the first dose of pembrolizumab.
4. Known contra-indication and/or hypersensitivity to PD1/PD-L1 antagonist and/or cytotoxic therapy.
5. Known contra-indication to cryoablation.
6. Abnormal coagulation contraindicating biopsy.
7. 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).
8. Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy.
9. Subjects who participated in an investigational drug or device study within 28 days prior to study entry.
10. Known infection with HIV, hepatitis B, or hepatitis C.
11. Females who are pregnant or breast-feeding.
12. Men or women refusing contraception.
13. 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.
14. Previous enrolment in the present study.
15. Individuals deprived of liberty or placed under legal guardianship.

Where this trial is running

Bordeaux, Gironde

• Institut Bergonié — Bordeaux, Gironde, France (RECRUITING)

Study contacts

• Principal investigator: Jean PALUSSIERE, MD — Institut Bergonié
• Study coordinator: Jean PALUSSIERE, MD

Conditions: Lung Adenocarcinoma, Cryotherapy Effect, Lung adenocarcinoma, immunotherapy, cryoablation