Dataset Information

A phase I/II study of stereotactic radiotherapy and pembrolizumab for oligometastatic renal tumours (RAPPORT): Clinical trial protocol.

ABSTRACT:

Background

The management of oligometastatic clear cell renal cell carcinoma (ccRCC) varies widely, ranging from observation to resection or systemic therapies. Prolonged survival has been observed following resection or stereotactic ablative body radiotherapy (SABR). Immunotherapy combinations have shown survival benefits, however, toxicity is higher than that for monotherapy and complete response rates remain less than 10%. The combination of effective local therapies in conjunction with immunotherapy may provide more durable control and pre-clinical models have suggested a synergistic immune-priming effect of SABR.

Objectives

and Methods: RAPPORT is a prospective, single arm, phase I/II study assessing the safety, efficacy and biological effects of single fraction SABR followed by pembrolizumab for oligometastatic ccRCC. The study will include 30 patients with histological confirmed ccRCC and 1-5 oligometastases, one or more of which must be suitable for SABR. Patients can have received prior systemic therapy but not prior immunotherapy. A single 20Gy of SABR is followed 5 days later by 8 cycles of 200 mg pembrolizumab, every 3 weeks. Adverse events are recorded using CTCAE V4.03 and tumour response evaluated by Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST 1.1). Tumour tissue and peripheral blood samples will be collected pre-, during and post-treatment to assess longitudinal changes in immune subsets.

Outcomes and significance

The RAPPORT study will provide important safety and early efficacy data on the combination of SABR and pembrolizumab in oligometastatic ccRCC and will provide an insight into the underlying biological effects of combination therapy.

Trial registration

clinicaltrials.gov ID NCT02855203.

SUBMITTER: Pryor D

PROVIDER: S-EPMC7807247 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Publications

A phase I/II study of stereotactic radiotherapy and pembrolizumab for oligometastatic renal tumours (RAPPORT): Clinical trial protocol.

Pryor David D Bressel Mathias M Lawrentschuk Nathan N Tran Ben B Mooi Jennifer J Lewin Jeremy J Azad Arun A Colyer Duncan D Neha Nitika N Shaw Mark M Chander Sarat S Neeson Paul P Moon Daniel D Cuff Katharine K Wood Simon S Murphy Declan G DG Sandhu Shahneen S Loi Sherene S Siva Shankar S

Contemporary clinical trials communications 20210106

<h4>Background</h4>The management of oligometastatic clear cell renal cell carcinoma (ccRCC) varies widely, ranging from observation to resection or systemic therapies. Prolonged survival has been observed following resection or stereotactic ablative body radiotherapy (SABR). Immunotherapy combinations have shown survival benefits, however, toxicity is higher than that for monotherapy and complete response rates remain less than 10%. The combination of effective local therapies in conjunction wi ...[more]

PMID: 33490707

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Project description:INTRODUCTION:Up to 50% of soft tissue sarcoma (STS) patients develop metastases in the course of their disease. Cytotoxic therapy is a standard treatment in this setting but yields average tumour response rates of 25% at first line and ?10% at later lines. In oligometastatic stage, stereotactic body radiation therapy (SBRT) allows reaching high control rates at treated sites (?80%) and is potentially equally effective to surgery in term of overall survival. In order to shift the balance towards antitumour immunity by multisite irradiation, radiation could be combined with inhibitors of the immunosuppressive pathways. METHODS AND ANALYSIS:STEREOSARC is a prospective, multicentric, randomised phase II, designed to evaluate the efficacy of SBRT associated with immunotherapy versus SBRT only. Randomisation is performed with a 2:1 ratio within two arms. The primary objective is to evaluate the efficacy, in term of progression-free survival (PFS) rate at 6 months, of immunomodulated stereotactic multisite irradiation in oligometastatic sarcoma patients. The secondary objectives include PFS by immune response criteria, overall survival, quality-of-life evaluation and developing mathematical models of tumour growth and dissemination predictive of oligometastatic versus polymetastatic evolution. Patients will be randomised in two groups: SBRT with atezolizumab and SBRT alone. The total number of included patients should be 103. TRIAL REGISTRATION:The trial is registered on ClinicalTrials.gov (ID: NCT03548428). ETHICS AND DISSEMINATION:This study has been approved by Comité de Protection des Personnes du sud-ouest et outre-mer 4 on 18 October 2019 (Reference CPP2019-09-076-PP) and from National Agency for Medical and Health products Safety (Reference: MEDAECNAT-2019-08-00004_2017-004239-35) on 18 September 2019.The results will be disseminated to patients upon individual request or through media release from scientific meetings. The results will be communicated through scientific meetings and publications.

Project description:BackgroundStereotactic ablative body radiotherapy (SABR) is one of the treatment options for oligometastatic renal cell carcinoma (RCC) but is limited by a lack of data to evaluate high-dose SABR to all/multiple sites.ObjectiveThis study retrospectively investigated the efficacy and prognostic factors of high-dose SABR for oligometastatic RCC patients.Design, setting, and participantsPatients with oligometastatic RCC on systemic therapy were retrospectively collected.Intervention(s)All patients were treated with SABR (40-50 Gy/5 fractions) for small tumors or partial-SABR (tumor center boosted with 6-8 Gy/3-5 fractions with 50-60 Gy/20-25 fractions to the whole tumor volume) for bulky tumors or tumors adjacent to critical organs.Outcome measurements and statistical analysisProgression-free survival (PFS) and overall survival (OS) were calculated.Results and limitationsIn total, 35 patients were enrolled, of which 88.5% had intermediate- or high-risk disease, with 60% on second- to fourth-line systemic therapy. The median follow-up time was 17 months. The median PFS and OS times were 11.3 and 29.7 months, respectively. Univariate analysis showed that an OS benefit was found in patients who received radiation before tyrosine kinase inhibitor (TKI) failure (p = 0.006) and where there was a short time interval (<six months) from being diagnosed with metastatic disease to undergoing radiotherapy (p = 0.046). Similar results were also found in PFS in patients who received radiation before TKI failure (p = 0.049) or within eight months (p = 0.047). There were certain differences in PFS (p = 0.033) between patients receiving radiotherapy with all lesions and those with selected tumors. In multivariate analysis, OS benefits were found in patients who received radiotherapy before TKI failure (p = 0.028). The limitations of this study include its retrospective design and the small patient cohort.ConclusionsThe early use of high-dose SABR to multi-lesions may improve survival. Partial-SABR for bulky lesions close to critical organs could be safely and effectively applied under certain circumstances.

Dataset Information

A phase I/II study of stereotactic radiotherapy and pembrolizumab for oligometastatic renal tumours (RAPPORT): Clinical trial protocol.

Background

Objectives

Outcomes and significance

Trial registration

Publications

A phase I/II study of stereotactic radiotherapy and pembrolizumab for oligometastatic renal tumours (RAPPORT): Clinical trial protocol.

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