Dataset Information

Phase II Trial of Stereotactic Ablative Radiation for Oligoprogressive Metastatic Kidney Cancer.

ABSTRACT:

Background

Patients with metastatic renal cell carcinoma (mRCC) treated with systemic therapy sometimes progress at limited sites.The best treatment approach for patients with oligoprogression remains unclear.

Objective

To determine the ability of stereotactic ablative radiation (SAbR) to extend ongoing systemic therapy in mRCC patients with oligoprogression.

Design, setting, and participants

A single-arm phase II clinical trial was conducted at a university medical center and county hospital, including 20 patients with mRCC on first- to fourth-line systemic therapy with three or fewer sites of progression (including new sites) involving ≤30% of all sites.

Intervention

SAbR to oligoprogressing metastases at outset and longitudinally, while radiated sites remain controlled and overall disease oligoprogressive.

Outcome measurements and statistical analysis

The primary objective was to extend ongoing systemic therapy by >6 mo in >40% of patients. Secondary endpoints included overall survival, toxicity, and patient-reported quality of life.

Results and limitations

Twenty patients were enrolled. Upfront and sequential SAbR was administered to a total of 37 sites. The local control rate was 100%. At a median follow-up of 10.4 mo (interquartile range: 5.8-16.4), SAbR extended the duration of the ongoing systemic therapy by >6 mo in 14 patients (70%, 95% confidence interval [CI]: 49.9-90.1). The median time from SAbR to the onset of new systemic therapy or death was 11.1 mo (95% CI: 4.5-19.3). The median duration of SAbR-aided systemic therapy was 24.4 mo (95% CI: 15.3-42.2). Median overall survival was not reached. One patient developed grade 3 gastrointestinal toxicity possibly related to treatment. There was no significant decline in quality of life. Limitations include nonrandomized design and a small patient cohort.

Conclusions

SAbR extended the duration of the ongoing systemic therapy for patients with oligoprogressive mRCC without undermining quality of life. These data support the evaluation of SAbR for oligoprogressive mRCC in a prospective randomized clinical trial.

Patient summary

Patients with metastatic kidney cancer on systemic therapy but progressing at limited sites may benefit from focused radiation to progressive sites. Focused radiation was safe and effective, and extended the duration of the ongoing systemic therapy.

SUBMITTER: Hannan R

PROVIDER: S-EPMC9090939 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Phase II Trial of Stereotactic Ablative Radiation for Oligoprogressive Metastatic Kidney Cancer.

Hannan Raquibul R Christensen Michael M Hammers Hans H Christie Alana A Paulman Brendan B Lin Dandan D Garant Aurelie A Arafat Waddah W Courtney Kevin K Bowman Isaac I Cole Suzanne S Sher David D Ahn Chul C Choy Hak H Timmerman Robert R Brugarolas James J

European urology oncology 20220102 2

<h4>Background</h4>Patients with metastatic renal cell carcinoma (mRCC) treated with systemic therapy sometimes progress at limited sites.The best treatment approach for patients with oligoprogression remains unclear.<h4>Objective</h4>To determine the ability of stereotactic ablative radiation (SAbR) to extend ongoing systemic therapy in mRCC patients with oligoprogression.<h4>Design, setting, and participants</h4>A single-arm phase II clinical trial was conducted at a university medical center ...[more]

PMID: 34986993

Similar Datasets

Project description:BackgroundWe describe a randomized, non-blinded Phase II interventional study to assess the safety and efficacy of stereotactic ablative radiotherapy (SABR) for hormone-sensitive oligometastatic prostate adenocarcinoma, and to describe the biology of the oligometastatic state using immunologic, cellular, molecular, and functional imaging correlates. 54 men with oligometastatic prostate adenocarcinoma will be accrued. The primary clinical endpoint will be progression at 6 months from randomization with the hypothesis that SABR to all metastases will forestall progression by disrupting the metastatic process. Secondary clinical endpoints will include local control at 6 months post-SABR, toxicity and quality of life, and androgen deprivation therapy (ADT)-free survival (ADT-FS). Further fundamental analysis of the oligometastatic state with be achieved through correlation with investigational 18F-DCFPyL PET/CT imaging and measurement of circulating tumor cells, circulating tumor DNA, and circulating T-cell receptor repertoires, facilitating an unprecedented opportunity to characterize, in isolation, the effects of SABR on the dynamics of and immunologic response to oligometastatic disease.Methods/designPatients will be randomized 2:1 to SABR or observation with minimization to balance assignment by primary intervention, prior hormonal therapy, and PSA doubling time. Progression after 6 months will be compared using Fisher's exact test. Hazard ratios and Kaplan-Meier estimates of progression free survival (PFS), ADT free survival (ADT-FS), time to locoregional progression (TTLP) and time to distant progression (TTDP) will be calculated based on an intention-to-treat. Local control will be assessed using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Withdrawal from the study prior to 6 months will be counted as progression. Adverse events will be summarized by type and grade. Quality of life pre- and post- SABR will be measured by Brief Pain Inventory.DiscussionThe ORIOLE trial is the first randomized, non-blinded Phase II interventional study in the North America evaluating the safety and efficacy of SABR in oligometastatic hormone-sensitive prostate cancer. Leading-edge laboratory and imaging correlates will provide unique insight into the effects of SABR on the oligometastatic state.Trial registrationsClinicalTrials.gov Identifier: NCT02680587. URL of Registry: https://clinicaltrials.gov/show/NCT02680587 Date of Registration: 02/08/2016. Date of First Participant Enrollment: 05/23/2016.

Project description:BACKGROUND:Stereotactic ablative body radiotherapy (SABR) is a non-invasive alternative to surgery to control primary renal cell cancer (RCC) in patients that are medically inoperable or at high-risk of post-surgical dialysis. The objective of the FASTRACK II clinical trial is to investigate the efficacy of SABR for primary RCC. METHODS:FASTRACK II is a single arm, multi-institutional phase II study. Seventy patients will be recruited over 3 years and followed for a total of 5 years. Eligible patients must have a biopsy confirmed diagnosis of primary RCC with a single lesion within a kidney, have ECOG performance ?2 and be medically inoperable, high risk or decline surgery. Radiotherapy treatment planning is undertaken using four dimensional CT scanning to incorporate the impact of respiratory motion. Treatment must be delivered using a conformal or intensity modulated technique including IMRT, VMAT, Cyberknife or Tomotherapy. The trial includes two alternate fractionation schedules based on tumour size: for tumours ?4 cm in maximum diameter a single fraction of 26Gy is delivered; and for tumours >?4 cm in maximum diameter 42Gy in three fractions is delivered. The primary outcome of the study is to estimate the efficacy of SABR for primary RCC. Secondary objectives include estimating tolerability, characterising overall survival and cancer specific survival, estimating the distant failure rate, describing toxicity and renal function changes after SABR, and assessment of cost-effectiveness of SABR compared with current therapies. DISCUSSION:The present study design allows for multicentre prospective validation of the efficacy of SABR for primary RCC that has been observed from prior single institutional and retrospective series. The study also allows assessment of treatment related toxicity, overall survival, cancer specific survival, freedom from distant failure and renal function post therapy. TRIAL REGISTRATION:Clinicaltrials.gov NCT02613819 , registered Nov 25th 2015.

Project description:Abstract Background Background: It is estimated that a significant number of patients presenting with metastatic RCC are either ineligible, not recommended for, or refuse surgery. There remains no well-established method for addressing the primary tumor in such patients. Stereotactic ablative radiotherapy (SABR) is a highly effective modality for the treatment of the primary tumor in RCC. Our study seeks to evaluate SABR as an alternative approach to treat the primary tumor in patients with metastatic RCC receiving immunotherapy, who are not recommended for surgery, or who decline surgery. The primary objective of the study is to determine whether the addition of SABR to the primary tumor in combination with immunotherapy improves outcomes compared to immunotherapy alone in patients with metastatic, unresected, renal cell carcinoma (RCC). The primary endpoint is nephrectomy and radiographic progression-free survival (nrPFS) with progression determined as per iRECIST criteria. Patients are eligible if they are not recommended for upfront surgery, have a primary tumor treatable with SABR, and are candidates for immunotherapy. Immunotherapy is physician’s choice and will include either two different immunotherapy regimens (IO-IO) or immunotherapy in combination with a VEGF inhibitor (IO-VEGF). Methods 240 patients will be randomized in a 2:1 ratio favoring SABR plus immunotherapy (n=160) as compared to standard of care immunotherapy alone (n=80). The sample size will provide 90% power at a one-sided alpha level of 0.05 to detect a hazard ratio for nrPFS of 0.61, i.e., a 40% reduction in the rate of events. One-year PFS in the nivolumab plus ipilmumab arm was 50% (n=550, intermediate/poor risk population). Checkmate 9ER (Choueiri 2021) showed a one-year PFS rate in patients receiving nivolumab plus Cabozantinib (n=323) of 45-58% (intermediate/poor risk population). We have therefore estimated a one-year nrPFS rate of 50% in the control (immunotherapy alone) arm for SAMURAI. We expect nephrectomies to contribute only a small fraction to the total nrPRS events. To detect a hazard ratio of 0.62, which corresponds under exponential distribution assumptions to an absolute 15% improvement in one-year nrPFS from 50% in the control group to 65% in the experimental arm (SABR plus immunotherapy), a total sample size of 240 patients will be enrolled. This design will provide 90% power, based on a one-sided logrank test at the 0.05 alpha level, with three years of accrual and two further years of follow-up. The expected number of nrPFS events is E=175. The calculations allow for a 10% non-eligible/early dropout rate. The trial is currently open and accruing through the NRG oncology cooperative group (NCT05327686).

Project description:ImportanceComplete metastatic ablation of oligometastatic prostate cancer may provide an alternative to early initiation of androgen deprivation therapy (ADT).ObjectiveTo determine if stereotactic ablative radiotherapy (SABR) improves oncologic outcomes in men with oligometastatic prostate cancer.Design, setting, and participantsThe Observation vs Stereotactic Ablative Radiation for Oligometastatic Prostate Cancer (ORIOLE) phase 2 randomized study accrued participants from 3 US radiation treatment facilities affiliated with a university hospital from May 2016 to March 2018 with a data cutoff date of May 20, 2019, for analysis. Of 80 men screened, 54 men with recurrent hormone-sensitive prostate cancer and 1 to 3 metastases detectable by conventional imaging who had not received ADT within 6 months of enrollment or 3 or more years total were randomized.InterventionsPatients were randomized in a 2:1 ratio to receive SABR or observation.Main outcomes and measuresThe primary outcome was progression at 6 months by prostate-specific antigen level increase, progression detected by conventional imaging, symptomatic progression, ADT initiation for any reason, or death. Predefined secondary outcomes were toxic effects of SABR, local control at 6 months with SABR, progression-free survival, Brief Pain Inventory (Short Form)-measured quality of life, and concordance between conventional imaging and prostate-specific membrane antigen (PSMA)-targeted positron emission tomography in the identification of metastatic disease.ResultsIn the 54 men randomized, the median (range) age was 68 (61-70) years for patients allocated to SABR and 68 (64-76) years for those allocated to observation. Progression at 6 months occurred in 7 of 36 patients (19%) receiving SABR and 11 of 18 patients (61%) undergoing observation (P = .005). Treatment with SABR improved median progression-free survival (not reached vs 5.8 months; hazard ratio, 0.30; 95% CI, 0.11-0.81; P = .002). Total consolidation of PSMA radiotracer-avid disease decreased the risk of new lesions at 6 months (16% vs 63%; P = .006). No toxic effects of grade 3 or greater were observed. T-cell receptor sequencing identified significant increased clonotypic expansion following SABR and correlation between baseline clonality and progression with SABR only (0.082085 vs 0.026051; P = .03).Conclusions and relevanceTreatment with SABR for oligometastatic prostate cancer improved outcomes and was enhanced by total consolidation of disease identified by PSMA-targeted positron emission tomography. SABR induced a systemic immune response, and baseline immune phenotype and tumor mutation status may predict the benefit from SABR. These results underline the importance of prospective randomized investigation of the oligometastatic state with integrated imaging and biological correlates.Trial registrationClinicalTrials.gov Identifier: NCT02680587.

Project description:BackgroundMost renal cell carcinomas (RCCs) are localized and managed by active surveillance, surgery, or minimally invasive techniques. Stereotactic ablative radiation (SAbR) may provide an innovative non-invasive alternative although prospective data are limited.ObjectiveTo investigate whether SAbR is effective in the management of primary RCCs.Design, setting, and participantsPatients with biopsy-confirmed radiographically enlarging primary RCC (≤5 cm) were enrolled. SAbR was delivered in either three (12 Gy) or five (8 Gy) fractions.Outcome measurements and statistical analysisThe primary endpoint was local control (LC) defined as a reduction in tumor growth rate (compared with a benchmark of 4 mm/yr on active surveillance) and pathologic evidence of tumor response at 1 yr. Secondary endpoints included LC by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1), safety, and preservation of kidney function. Exploratory tumor cell-enriched spatial protein and gene expression analysis were conducted on pre- and post-treatment biopsy samples.Results and limitationsTarget accrual was reached with the enrollment of 16 ethnically diverse patients. Radiographic LC at 1 yr was observed in 94% of patients (15/16; 95% confidence interval: 70, 100), and this was accompanied by pathologic evidence of tumor response (hyalinization, necrosis, and reduced tumor cellularity) in all patients. By RECIST, 100% of the sites remained without progression at 1 yr. The median pretreatment growth rate was 0.8 cm/yr (interquartile range [IQR]: 0.3, 1.4), and the median post-treatment growth rate was 0.0 cm/yr (IQR: -0.4, 0.1, p < 0.002). Tumor cell viability decreased from 4.6% to 0.7% at 1 yr (p = 0.004). With a median follow-up of 36 mo for censored patients, the disease control rate was 94%. SAbR was well tolerated with no grade ≥2 (acute or late) toxicities. The average glomerular filtration rate declined from a baseline of 65.6 to 55.4 ml/min at 1 yr (p = 0.003). Spatial protein and gene expression analyses were consistent with the induction of cellular senescence by radiation.ConclusionsThis clinical trial adds to the growing body of evidence suggesting that SAbR is effective for primary RCC supporting its evaluation in comparative phase 3 clinical trials.Patient summaryIn this clinical trial, we investigated a noninvasive treatment option of stereotactic radiation therapy for the treatment of primary kidney cancer and found that it was safe and effective.

Dataset Information

Phase II Trial of Stereotactic Ablative Radiation for Oligoprogressive Metastatic Kidney Cancer.

Background

Objective

Design, setting, and participants

Intervention

Outcome measurements and statistical analysis

Results and limitations

Conclusions

Patient summary

Publications

Phase II Trial of Stereotactic Ablative Radiation for Oligoprogressive Metastatic Kidney Cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets