Lung Cancer Cryo-Activation as a Novel Approach to Augment Immunotherapy Efficacy (CRYOVATE)

NCT04793815 | Completed DMC

• 1 other identifier: CE20.365
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief 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. 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

Conditions

Non-small Cell Lung Cancer Metastatic; Cryotherapy Effect

Keywords

NSCLC; Cryo-activation; Anti-PD-1

Outcome Measures

Primary Outcomes (1)

• 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.

  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)

  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)

  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)

  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)

Study Arms (1)

Cryo-activation and anti-PD-1 monotherapy combination

EXPERIMENTAL

Procedure: Cryo-activation; Drug: Pembrolizumab

Interventions

Cryo-activation PROCEDURE

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.

Also known as: Endoscopic cryotherapy

Cryo-activation and anti-PD-1 monotherapy combination

Pembrolizumab DRUG

Following the cryo-activation procedure, patients will sequentially be treated with pembrolizumab (anti-PD-1) monotherapy.

Also known as: Anti-PD-1

Cryo-activation and anti-PD-1 monotherapy combination

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Centre hospitalier de l'Université de Montréal (CHUM): lead

Study Sites (1)

Centre hospitalier de l'Université de Montréal (CHUM)

Montreal, Quebec, H2X 3E4, Canada

Location

MeSH Terms

Interventions

pembrolizumab; spartalizumab

Study Officials

• Moishe Liberman, MD PhD

  CHUM

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: February 24, 2021
• First Posted: March 11, 2021
• Study Start: May 1, 2021
• Primary Completion: June 27, 2023
• Study Completion: June 27, 2023
• Last Updated: June 29, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)