Cryoablation and immunotherapy: an overview of evidence on its synergy

Aarts, B. M.; Klompenhouwer, E. G.; Rice, S. L.; Imani, F.; Baetens, T.; Bex, A.; Horenblas, S.; Kok, M.; Haanen, J. B. A. G.; Beets-Tan, R. G. H.; Gómez, F. M.

doi:10.1186/s13244-019-0727-5

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Table 3 Overview of clinical trials of cryoablation and immunotherapy

From: Cryoablation and immunotherapy: an overview of evidence on its synergy

Cancer type	Tumour stage	Study phase	Study design	Therapy	End points	End date	Centre	Identifier
Breast cancer	Early/resectable disease	Pilot	Open label single arm	Pre-operative ipilimumab + nivolumab + cryoablation	Safety: number of adverse events, no secondary end points.	June 2019	Memorial Sloan Kettering Cancer Center, USA	NCT02833233
Breast cancer	Resectable disease	II	Prospective randomized parallel interventional	Peri-operative cryoablation, ipilimumab nivolumab vs pre-operative care	Distant disease-free survival*	May 2021	Cedars-Sinai Medical Center, USA	NTC03546686
Renal cell carcinoma	Metastatic disease	I	Open label single arm	Tremelimumab +/− cryoablation before surgery	Objective response rate by irRC*	March 2021	MD Anderson, USA	NCT02626130
Renal cell carcinoma	Stage I	–	Prospective observational cohort	Immune response of cryoablation vs RFA vs LPN	Immune response: number of leucocytes in tissue samples post ablation.	June 2019	UC Irvine, USA	NCT03409224
Prostate cancer	Localized disease	Basic science	Open label single arm	Immune response profile after total cryotherapy, focal cryotherapy, SBRT and radical prostatectomy	Evaluate change in blood cytokine profile	Sept 2019	Winthrop University Hospital, USA	NCT03331367
	Metastatic disease	II	Open label single arm	Pembrolizumab and cryosurgery in combination with short term androgen ablation	Proportion of men with PSA < 0.6 ng/mL PD-1/PDL-1 expression	Nov 2018	Sidney Kimmel Comprehensive Cancer Center, USA	NCT02489357
	Stage I tm IIB	I	Prospective randomized open label clinical trial	GM-CSF after cryoablation	Change in B cell, T cells and PSA levels	Dec 2018	University of Colorado Cancer Center, USA	NCT02250014
	Castration resistant disease with positive lymph nodes	I	Open label single arm	Cryoablation plus intratumoural immature dendritic cells	Maximum tolerated dose*	April 2019	Haukeland University Hospital, Norwegian	NCT02423928
Lung cancer	Stage IV	II	Open label single arm	Core needle biopsy and cryoablation added to continued treatment with immune checkpoint inhibitor	Response by RECIST*	March 2025	Massachusetts General Hospital, USA	NCT03290677
Melanoma	Stage III tm IV cutaneous melanoma	I + II	Open label single arm	Dendritic cell therapy after cryosurgery in combination with pembrolizumab	Response by RECIST Clinical benefit*	Oct 2022	Mayo Clinic, USA	NCT03325101
Melanoma	Stage IV, HLA-A2 + no curative disease	I	Open label single arm	Radiofrequency therapy + RFA/CA+ GM-CSF injection	Level of immune response by heat shock protein and lymphocyte Response by RECIST*	May 2018	Mayo Clinic, USA	NCT00568763
Other	Metastatic Colorectal cancer	I/IIb	Open label single arm	Combining cryoablation with intra-lesional immunotherapy with AlloStim® with dose escalation	Safety of increased frequency of dosing* Tumour response RECIST and histopathology HRQoL	Feb 2018	MD Anderson Medical Center, USA	NCT02380443 NB this study was first designed in BC
	Palliative stetting of HCC or BTC	I/II	Open label single arm	Tremelimumab and durvalumab + RFA/CA/TACE	PFS*	Apr 2021	National institutes of health clinical centre, USA	NCT02821754
	Palliative stetting of HCC or BTC stage B and C	I	Clinical prospective non-randomised	Tremelimumab + RFA/CA/SBRT/TACE	Response Rate Time to tumour progression Overall survival*	Dec 2018	National Institutes of Health Clinical Center, USA	NCT01853618
Other	Non-Hodgkin lymphoma	I/II	Open label single arm	Intratumoral DC therapy after cryosurgery and pembrolizumab	Maximum tolerated dose* Complete responses Disease free survival rate Duration of response OS, PFS, HRQoL	Feb 2021	Mayo Clinic, USA	NCT03035331
	1. Oesophageal cancer, 2. Tongue cancer, 3. Ovarian cancer, 4. Laryngeal cancer, 5. Pharyngeal cancer, 6. Cervical cancer 7. Tumours in transplanted livers 8. Sarcoma	I/II	Open label single arm trial	Cryoablation and NK cell immunotherapy	Response, PFS, OS by RECIST*	Jul 2019	Cancer Institute in Fuda Cancer Hospital, China	NCT02843581 NCT02849379 NCT02849353 NCT02849314 NCT02849327 NCT02849340 NCT02849015 NCT02849366
	1. Breast cancer, 2. Liver cancer, 3. Lung cancer, 4. Gastric cancer, 5. Colorectal cancer, 6. Pancreatic cancer 7. Kidney cancer	II	Prospective randomized triple arm study	Activated CIK cells + anti-bispecific antibody with or without cryoablation vs conventional therapy	Objective response rate PFS TTP*	April 2021	Fuda Cancer Hospital, China	NTC03524261 NTC03484962 NTC03501056 NTC03554395 NTC03524274 NTC03509298 NTC03540199

RECIST response evaluation criteria in solid tumours, irRC immune-related response criteria, PFS progression-free survival, OS overall survival, CR complete response, PR partial response, HRQoL health-related quality of life, DSS disease specific survival, LHRH agonist luteinizing-hormone releasing-hormone agonist, TTP time tumour progression, RFA radiofrequency ablation, CA cryoablation, SBRT stereotactic body radiotherapy, DC dendritic cell, CIK cytokine-induced killer cells, NK natural killer, TACE transarterial chemo-embolisation, GM-CSF granulocyte-macrophage colony-stimulating factor, LPN laparoscopic partial nephrectomy, PSA prostate specific antigen, PD-1 programmed cell death protein, PDL-1 programmed cell death ligand
*Safety has been performed in all studies by number of adverse events

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