TY - JOUR

T1 - Randomised phase II trial of stereotactic body radiotherapy in combination with checkpoint inhibitors in metastatic castration-resistant prostate cancer (CheckPRO)

T2 - a study protocol

AU - Spindler, Nicklas Juel

AU - Persson, Gitte Fredberg

AU - Theile, Susann

AU - Nielsen, Dorte Lisbeth

AU - Høgdall, Estrid V.

AU - Al-Farra, Gina

AU - Hendel, Helle Westergren

AU - Lorentzen, Torben

AU - Svane, Inge Marie

AU - Lindberg, Henriette

AU - Eefsen, Rikke Løvendahl

N1 - Publisher Copyright: © 2023 Author(s). Published by BMJ.

PY - 2023

Y1 - 2023

N2 - Introduction Immunotherapy with checkpoint inhibitors (CPIs) has revolutionised cancer treatment but has no convincing effect in metastatic castration-resistant prostate cancer (mCRPC). It has been suggested that a combination of CPI and hypofractionated stereotactic body radiotherapy (SBRT) may work synergistically, and recent trials have supported this. We hypothesise that adding SBRT to CPI treatment can improve response rates in patients with mCRPC. Methods and analysis The CheckPRO trial is an open-label, randomised, two-stage, phase II trial. We aim to enrol and randomise 80 evaluable patients with mCRPC who progressed following ≥2 lines of treatment. Enrolment started in November 2019 with 38 months expected enrolment period. The participants receive treatment for 52 weeks including four cycles of ipilimumab and nivolumab with or without concomitant SBRT (24 Gray in three fractions) to a single soft tissue or bone metastasis, followed by 10 cycles of nivolumab. Participants are followed until progression, death, or for 12 months after the end of treatment. Co-primary endpoints are the objective response rate and prostate-specific antigen (PSA) response rate. Secondary endpoints include safety, radiographic progression-free survival, clinical benefit rate, duration of response, PSA-progression-free survival beyond 12 weeks, quality of life and overall survival. Exploratory endpoints include translational analyses of tumour biopsies and consecutive blood samples. Biopsies from metastatic sites are collected at baseline, before the third treatment and at the end of treatment. Blood sampling for immune monitoring and circulating tumour DNA is performed consecutively at baseline and every radiographic assessment. Ethics and dissemination This study follows the Helsinki Declaration and is approved by the Danish Ethics Committee System (journal no. H-19016100). All participants must receive written and oral information and provide a signed informed consent document prior to inclusion. The study results will be published in an international peer-review journal. Trial registration number EudraCT number: 2018-003461-34. clinicaltrials.gov ID NCT05655715.

AB - Introduction Immunotherapy with checkpoint inhibitors (CPIs) has revolutionised cancer treatment but has no convincing effect in metastatic castration-resistant prostate cancer (mCRPC). It has been suggested that a combination of CPI and hypofractionated stereotactic body radiotherapy (SBRT) may work synergistically, and recent trials have supported this. We hypothesise that adding SBRT to CPI treatment can improve response rates in patients with mCRPC. Methods and analysis The CheckPRO trial is an open-label, randomised, two-stage, phase II trial. We aim to enrol and randomise 80 evaluable patients with mCRPC who progressed following ≥2 lines of treatment. Enrolment started in November 2019 with 38 months expected enrolment period. The participants receive treatment for 52 weeks including four cycles of ipilimumab and nivolumab with or without concomitant SBRT (24 Gray in three fractions) to a single soft tissue or bone metastasis, followed by 10 cycles of nivolumab. Participants are followed until progression, death, or for 12 months after the end of treatment. Co-primary endpoints are the objective response rate and prostate-specific antigen (PSA) response rate. Secondary endpoints include safety, radiographic progression-free survival, clinical benefit rate, duration of response, PSA-progression-free survival beyond 12 weeks, quality of life and overall survival. Exploratory endpoints include translational analyses of tumour biopsies and consecutive blood samples. Biopsies from metastatic sites are collected at baseline, before the third treatment and at the end of treatment. Blood sampling for immune monitoring and circulating tumour DNA is performed consecutively at baseline and every radiographic assessment. Ethics and dissemination This study follows the Helsinki Declaration and is approved by the Danish Ethics Committee System (journal no. H-19016100). All participants must receive written and oral information and provide a signed informed consent document prior to inclusion. The study results will be published in an international peer-review journal. Trial registration number EudraCT number: 2018-003461-34. clinicaltrials.gov ID NCT05655715.

KW - adult oncology

KW - prostate disease

KW - protocols & guidelines

KW - radiotherapy

U2 - 10.1136/bmjopen-2022-063500

DO - 10.1136/bmjopen-2022-063500

M3 - Journal article

C2 - 36717150

AN - SCOPUS:85147170057

VL - 13

JO - BMJ Open

JF - BMJ Open

SN - 2044-6055

IS - 1

M1 - e063500

ER -