Non-small Cell Lung Cancer MetastaticNCT04793815
Lung Cancer Cryo-Activation as a Novel Approach to Augment Immunotherapy Efficacy (CRYOVATE)
A study testing Cryo-activation and Pembrolizumab in people with Non-small Cell Lung Cancer Metastatic and Cryotherapy Effect, run by Centre hospitalier de l'Université de Montréal (CHUM) at 1 site in Canada.
Trial summary
Cryo-activation involves the insertion of a cryoprobe in the tumor bed with subsequent cell necrosis and tumor antigens release. Such technique has the potential to induce immune-specific reactions influencing cancer cells outside of the ablated region. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-small Cell Lung Cancer Metastatic, Cryotherapy Effect
- What is being tested?
- Cryo-activation and Pembrolizumab
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteCanada
- Study dates
- 1 May 2021to 27 Jun 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
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
- Patients must be ≥18 years of age.
- Patients must have histologically or cytologically confirmed NSCLC that is advanced/metastatic or unresectable and for which no curative therapy is available.
- Patients must present PD-L1 tumor proportion score (TPS) ≥50% in order to be eligible for first-line pembrolizumab monotherapy.
- Patients may have had prior adjuvant or neoadjuvant chemotherapy for NSCLC providing completed at least 12 months prior to relapse. Patients may not have had anti-PD-1/PD-L1 agents in the adjuvant or neoadjuvant setting.
- Patients must have an ECOG performance status 0 or 1, and a minimum life expectancy of at least 12 weeks.
- Patients must have clinically and/or radiologically documented disease with at least one lesion measurable as defined by RECIST 1.1 (excluding the lesion selected for cryo-activation). All radiology studies must be performed within 21 days prior to enrollment (within 28 days if negative). The criteria for defining measurable disease are as follows:
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- CT scan (with slice thickness of 5 mm) lesion of ≥10 mm - longest diameter (≥15 mm for nodal lesions, measured in short axis)
- Chest x-ray ≥20 mm
- Physical exam (using calipers) ≥10 mm
- Primary and/or secondary lung lesions or proven metastatic lymph nodes must be accessible to flexible bronchoscopy, endobronchial ultrasound (EBUS) or endoscopic ultrasound (EUS).
- Patients must have disease amenable to biopsy and be willing and able to undergo tumor biopsies at baseline, at 4 weeks following anti-PD-1 initiation and at disease progression.
Who cannot join
- Patients may NOT previously have received other immunotherapy agents, including anti-PD-1/PD-L1 or anti-CTLA-4 agent.
- Patients may NOT have received or be eligible for treatment with standard targeted therapies; patients whose tumor samples have targetable alterations, such as EGFR, ALK, BRAF or ROS1 are not eligible (K-ras mutations are not excluded).
- Patients with prior history of autoimmune disorders, active hepatitis B, untreated hepatitis C or uncontrolled human immunodeficiency virus (HIV) or untreated tuberculosis and patients treated with of immunosuppressive agents within 14 days of study drug administration are NOT eligible.
- Patients being treated with systemic corticosteroids at doses that exceed 10mg/day of prednisone (or dosing equivalents)
- Patients may not be anticoagulated with any systemic anticoagulants which cannot be held for the appropriate half-life wash-out prior to the bronchoscopic procedures (Clopidogrel, Warfarin, Heparin, etc.). Aspirin is not a contraindication.
- Patients requiring supplemental oxygen therapy at home or with saturation of less than 90% on room air.
- Allergy to topical lidocaine required for local anesthesia during bronchoscopy.
Trial locations and contacts
1 site in 1 country.
Canada1 site
Centre hospitalier de l'Université de Montréal (CHUM)
Montreal, Quebec, H2X 3E4
About this study
Official title: Lung Cancer Cryo-Activation as a Novel Approach to Improve Cancer Immunogenicity and Augment Immunotherapy Efficacy
Cryo-activation involves the insertion of a cryoprobe in the tumor bed with subsequent cell necrosis and tumor antigens release. Such technique has the potential to induce immune-specific reactions influencing cancer cells outside of the ablated region. The addition of cryo-activation to immune-checkpoint blockers (ICB) in the advanced NSCLC setting could represent a synergistic therapeutic avenue in order to potentiate treatment responses
Read the detailed description
Innovative ablation techniques have gained momentum in the last decade in order to offer alternative approaches to patients not amenable to conventional surgery. Cryoablation, a procedure by which tumor cell death is induced through cycles of freezing and thawing, represents such a pioneering technique.
The procedure involves the insertion of a cryoprobe in the tumor bed with subsequent application of very low temperatures leading to cell necrosis and tumor antigens release. In the absence of significant heat-related denaturation seen in other ablative therapy techniques (microwave, radio frequency, steam, HIFU, etc.) and as intracellular content remains in circulation following cryo-activation, it is hypothesized that such technique has the potential to induce immune-specific reactions influencing cancer cells outside of the ablated region.
This phenomenon would be reminiscent of the abscopal effect, a reaction mediated by locoregional radiotherapy exposure with the potential to trigger a systemic immune response prompting metastatic disease regression. While such immune activation would in itself be insufficient to eradicate tumor cells at distant sites, the addition of immunotherapy through checkpoint inhibition in the advanced setting could represent a synergistic therapeutic avenue in order to potentiate treatment responses in patients with NSCLC.
A phase I/II clinical trial will be conducted in order to evaluate the safety and efficacy of cryo-activation therapy in patients with previously untreated advanced NSCLC amenable to anti-PD-1 monotherapy (i.e. PD-L1 ≥50%).
- Being tested
- Cryo-activation, Pembrolizumab
- Keywords
- NSCLC, Cryo-activation, Anti-PD-1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cryo-activationProcedure or surgery
Also called Endoscopic cryotherapy
The cryo-activation procedure involves the insertion of a cryoprobe in the tumor bed with subsequent application of very low temperatures leading to cell necrosis and tumor antigens release.
PembrolizumabDrug
Also called Anti-PD-1
Following the cryo-activation procedure, patients will sequentially be treated with pembrolizumab (anti-PD-1) monotherapy.
| Study group | Role | What they receive |
|---|---|---|
| Cryo-activation and anti-PD-1 monotherapy combination | Experimental | Not described Receives: Procedure: Cryo-activation; Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Best overall response rate (BORR; change from baseline)
Proportion of patients experiencing either complete response (CR) or partial response (PR) as their best overall response.
The best overall response represents a change on radiological (computed tomography) follow-up and is defined as the best response from start of treatment until disease progression.
Measured: every 8 weeks (until disease progression or for a maximum pembrolizumab treatment duration of 2 years), every 3 months thereafter (for up to a total of 5 years)
Secondary outcomes (3)
Incidence of treatment-related adverse events (Safety and tolerability)
Rate of complications, adverse reactions or treatment-induced toxicities according to the Common Terminology Criteria for Adverse Events (CTCAE v5.0)
Measured: every 8 weeks (until disease progression or for a maximum pembrolizumab treatment duration of 2 years), every 3 months thereafter (for up to a total of 5 years)
Progression-free survival (PFS)
Progression-free survival (PFS) will be calculated from the date of first anti-PD-1 dose until the date of first radiologically documented disease progression (PD) or date of death from any cause, whichever comes first, assessed up to 60 months following first anti-PD-1 dose
Measured: every 8 weeks (until disease progression or for a maximum pembrolizumab treatment duration of 2 years), every 3 months thereafter (for up to a total of 5 years)
Overall survival (OS)
Overall survival (OS) will be calculated from the date of first anti-PD-1 dose until the date of death from any cause, assessed up to 60 months following first anti-PD-1 dose
Measured: every 8 weeks (until disease progression or for a maximum pembrolizumab treatment duration of 2 years), every 3 months thereafter (for up to a total of 5 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Mar 2021
- Study start1 May 2021
- Primary completion27 Jun 2023
- Study completion27 Jun 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-small Cell Lung Cancer MetastaticStudies of the same condition, open and under way.
- More trials run by Centre hospitalier de l'Université de Montréal (CHUM)The sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Cryo-activation therapy will be performed in patients with advanced NSCLC (PD-L1≥50%) prior to ICB monotherapy in order to transform 'cold' tumors into 'warm' tumors, with the intent to improve ICB efficacy.
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Moishe Liberman, MD PhD, Principal investigator, CHUM
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04793815
- Sponsor's protocol ID
- CE20.365
- Status last verified
- Jun 2023
- First submitted
- 24 Feb 2021
- Last updated
- 29 Jun 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Lung Cancer Cryo-Activation as a Novel Approach to Improve Cancer Immunogenicity and Augment Immunotherapy Efficacy
- ClinicalTrials.gov ID
- NCT04793815
- Acronym / sponsor ID
- CE20.365
- Keywords
- NSCLC, Cryo-activation, Anti-PD-1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Centre hospitalier de l'Université de Montréal (CHUM)University, hospital or other
- Study start
- 1 May 2021 (actual)
- Primary completion
- 27 Jun 2023 (actual)
- Study completion
- 27 Jun 2023 (actual)
- First posted
- 11 Mar 2021 (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.
Cryo-activation involves the insertion of a cryoprobe in the tumor bed with subsequent cell necrosis and tumor antigens release. Such technique has the potential to induce immune-specific reactions influencing cancer cells outside of the ablated region. The addition of cryo-activation to immune-checkpoint blockers (ICB) in the advanced NSCLC setting could represent a synergistic therapeutic avenue in order to potentiate treatment responses
Detailed description
Innovative ablation techniques have gained momentum in the last decade in order to offer alternative approaches to patients not amenable to conventional surgery. Cryoablation, a procedure by which tumor cell death is induced through cycles of freezing and thawing, represents such a pioneering technique.
The procedure involves the insertion of a cryoprobe in the tumor bed with subsequent application of very low temperatures leading to cell necrosis and tumor antigens release. In the absence of significant heat-related denaturation seen in other ablative therapy techniques (microwave, radio frequency, steam, HIFU, etc.) and as intracellular content remains in circulation following cryo-activation, it is hypothesized that such technique has the potential to induce immune-specific reactions influencing cancer cells outside of the ablated region.
This phenomenon would be reminiscent of the abscopal effect, a reaction mediated by locoregional radiotherapy exposure with the potential to trigger a systemic immune response prompting metastatic disease regression. While such immune activation would in itself be insufficient to eradicate tumor cells at distant sites, the addition of immunotherapy through checkpoint inhibition in the advanced setting could represent a synergistic therapeutic avenue in order to potentiate treatment responses in patients with NSCLC.
A phase I/II clinical trial will be conducted in order to evaluate the safety and efficacy of cryo-activation therapy in patients with previously untreated advanced NSCLC amenable to anti-PD-1 monotherapy (i.e. PD-L1 ≥50%).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Cryo-activation therapy will be performed in patients with advanced NSCLC (PD-L1≥50%) prior to ICB monotherapy in order to transform 'cold' tumors into 'warm' tumors, with the intent to improve ICB efficacy.
| Arm | Type | Receives |
|---|---|---|
| Cryo-activation and anti-PD-1 monotherapy combination | Experimental | Procedure: Cryo-activation, Drug: Pembrolizumab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Patients must be ≥18 years of age.
- Patients must have histologically or cytologically confirmed NSCLC that is advanced/metastatic or unresectable and for which no curative therapy is available.
- Patients must present PD-L1 tumor proportion score (TPS) ≥50% in order to be eligible for first-line pembrolizumab monotherapy.
- Patients may have had prior adjuvant or neoadjuvant chemotherapy for NSCLC providing completed at least 12 months prior to relapse. Patients may not have had anti-PD-1/PD-L1 agents in the adjuvant or neoadjuvant setting.
- Patients must have an ECOG performance status 0 or 1, and a minimum life expectancy of at least 12 weeks.
Key exclusion criteria (7 listed)
- Patients may NOT previously have received other immunotherapy agents, including anti-PD-1/PD-L1 or anti-CTLA-4 agent.
- Patients may NOT have received or be eligible for treatment with standard targeted therapies; patients whose tumor samples have targetable alterations, such as EGFR, ALK, BRAF or ROS1 are not eligible (K-ras mutations are not excluded).
- Patients with prior history of autoimmune disorders, active hepatitis B, untreated hepatitis C or uncontrolled human immunodeficiency virus (HIV) or untreated tuberculosis and patients treated with of immunosuppressive agents within 14 days of study drug administration are NOT eligible.
- Patients being treated with systemic corticosteroids at doses that exceed 10mg/day of prednisone (or dosing equivalents)
- Patients may not be anticoagulated with any systemic anticoagulants which cannot be held for the appropriate half-life wash-out prior to the bronchoscopic procedures (Clopidogrel, Warfarin, Heparin, etc.). Aspirin is not a contraindication.
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 |
|---|---|---|
| Cryo-activationAlso: Endoscopic cryotherapyThe cryo-activation procedure involves the insertion of a cryoprobe in the tumor bed with subsequent application of very low temperatures leading to cell necrosis and tumor antigens release. | Procedure or surgery | Cryo-activation and anti-PD-1 monotherapy combination |
| PembrolizumabAlso: Anti-PD-1Following the cryo-activation procedure, patients will sequentially be treated with pembrolizumab (anti-PD-1) monotherapy. | Drug | Cryo-activation and anti-PD-1 monotherapy combination |
Primary outcome
Best overall response rate (BORR; change from baseline)
Time frame: every 8 weeks (until disease progression or for a maximum pembrolizumab treatment duration of 2 years), every 3 months thereafter (for up to a total of 5 years)
Proportion of patients experiencing either complete response (CR) or partial response (PR) as their best overall response. The best overall response represents a change on radiological (computed tomography) follow-up and is defined as the best response from start of treatment until disease progression.
3 secondary outcomes
Incidence of treatment-related adverse events (Safety and tolerability)
Time frame: every 8 weeks (until disease progression or for a maximum pembrolizumab treatment duration of 2 years), every 3 months thereafter (for up to a total of 5 years)
Progression-free survival (PFS)
Time frame: every 8 weeks (until disease progression or for a maximum pembrolizumab treatment duration of 2 years), every 3 months thereafter (for up to a total of 5 years)
Overall survival (OS)
Time frame: every 8 weeks (until disease progression or for a maximum pembrolizumab treatment duration of 2 years), every 3 months thereafter (for up to a total of 5 years)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jun 2023.
- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
Moishe Liberman, MD PhD principal investigator
CHUM
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cryo-activation and Pembrolizumab in people with Non-small Cell Lung Cancer Metastatic and Cryotherapy Effect, run by Centre hospitalier de l'Université de Montréal (CHUM) at 1 site in Canada.
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 11 inclusion and 7 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: finished, as of the sponsor's last update on 29 Jun 2023. 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 Canada. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Best overall response rate (BORR; change from baseline) (time frame: every 8 weeks (until disease progression or for a maximum pembrolizumab treatment duration of 2 years), every 3 months thereafter (for up to a total of 5 years)). 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 29 Jun 2023.