Single vs. Multiple Fraction Trial of Stereotactic Ablative Radiotherapy for Comprehensive Treatment of Oligometastases/Progression

Quality of Life Clinical Trial

Official title:

Single vs. Multiple Fraction Non-Inferiority Trial of Stereotactic Ablative Radiotherapy for the Comprehensive Treatment of Oligo-metastases/Progression: SIMPLIFY-SABR-COMET

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05784428
• Other study ID #: SIMPLIFY-SABR-COMET
• Status: Not yet recruiting
• Phase: N/A
• Start date: March 1, 2024
• Est. completion date: March 30, 2034

Study information

• Verified date: February 2023
• Source: British Columbia Cancer Agency
• Contact: Robert Olson, MD, MSC, FRCPC
• Phone: 250-645-7300
• Email: rolson2[@]bccancer.bc.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Stereotactic Ablative Radiotherapy (SABR) is a modern RT technique that delivers high doses of radiation to small tumor targets using highly conformal techniques, while trying to avoid healthy tissues and organs. However, SABR treatment requires increased planning, treatment time, cost and potential for higher toxicity due to the higher dose. The purpose of this study is to compare single fraction (SF) SABR vs. multiple fraction (MF) SABR in regards to toxicities, progression-free survival, quality of life (QoL), and cost-effectiveness. In a subset of patients, we will also compare patient QoL, hospitalization rates, and cost-effectiveness between patients who complete QoL questionnaires, record symptoms and receive healthcare provider-guided intervention vs. patients who complete QoL questionnaires only.

Description:

Radiation can be delivered in multiple fractions, or doses, and can take up to several weeks or months of treatment depending on the type of cancer. Radiation can also be offered in a single fraction. Both techniques have evidence for use in clinical care. Multiple fraction is offered to reduce the amount of radiation given at a single time that could reduce late toxicities. However, single fraction radiotherapy is more cost-effective and saves patient time. With this trial, we will compare single fraction vs. multiple fraction in regards to their impact on toxicity, progression-free survival: time from randomization to disease progression at any site or death, lesional control rate: lesion size post-SABR, quality of life and cost-effectiveness. In a subset of sites, we will also investigate the impact of healthcare-provider guided intervention on quality of life. Questionnaires capture various symptoms such as pain, fatigue and information relating to physical, social, and mental wellbeing. This information can help shed light on patient experience and provide a better understanding of the effects of radiation therapy. In this trial, we will compare quality of life questionnaire completion, symptom reporting and healthcare-provider guided intervention vs. quality of life questionnaire completion alone, in regards to patient quality of life. Hospitalization rates and frequency of emergency department visits will also be investigated. Sample size: The total sample size of 598 for this trial was calculated based on the primary endpoint of toxicity for the single vs. multiple fraction SABR randomization. Calculations were performed based on the results of the SABR-5 trial and our clinical judgement. Quality Assurance: Radiation treatments are based on the current phase III SABR-COMET-3 trial and as per recent clinical evidence. All treatments will be planned as per protocol including computed tomography (CT) simulation, organs at risk contouring and undergo a quality assurance process. For the subset of sites involved in the second randomization, training will be provided to patients on the use of Noona, a patient-reported outcome platform.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 598
• Est. completion date: March 30, 2034
• Est. primary completion date: March 30, 2034
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 1-5 current oligometastatic or oligo-progressive lesions
• Age 18 years or older
• Able to provide informed consent
• Able to complete electronic entry of patient reported outcomes and questionnaires independently or with assistance from a caregiver/family/friend/research staff using electronic methods after providing consent to email use.
• Life expectancy > 6 months
• Histologically confirmed malignancy with metastatic disease detected on imaging. Biopsy of metastasis is preferred, but not required.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Controlled primary tumor: defined as at least 3 months since original tumor treated radically, with no progression at primary site (can be considered controlled if no evidence of the primary tumour on imaging [e.g. primary unknown])
• A history and physical examination, including ECOG performance status, performed within 6 weeks prior to enrollment
• Patient has had a CT chest, abdomen and pelvis or PET-CT within 8 weeks prior to enrollment, and within 12 weeks prior to treatment
• Patient has had a nuclear bone scan (if no positron emission tomography-computed tomography [PET-CT]) within 8 weeks prior to enrollment, and within 12 weeks prior to treatment
• Patient has had CT or MRI brain imaging if primary has a propensity for central nervous system metastases within 8 weeks prior to enrollment, and within 12 weeks prior to treatment.
• For patients with known spine metastases, patient has had MRI spine imaging within 8 weeks prior to enrollment, and with 12 weeks prior to treatment.
• If solitary lung nodule for which biopsy is unsuccessful or not possible, patient has had an FDG (fluorodeoxyglucose) PET scan or CT (chest, abdomen, pelvis) and bone scan within 8 weeks prior to enrollment, and within 12 weeks prior to treatment
• If colorectal primary with rising Carcinoembryonic antigen (CEA), but equivocal imaging, patient has had an FDG PET scan within 8 weeks prior to enrollment, and within 12 weeks prior to treatment
• Patient is judged able to:
• Maintain a stable position during therapy
• Tolerate immobilization device(s) that may be required to deliver SABR safely
• Negative pregnancy test for People of Child-Bearing Potential (POCBP) within 4 weeks of RT start date Waivers to inclusion criteria will NOT be allowed.

Exclusion Criteria:

• Uncontrolled concurrent malignant cancer
• Lesion in femoral bone requiring surgical fixation
• No chemotherapy agents (cytotoxic, or molecularly targeted agents) will be used within the period of time commencing 1 week prior to radiation, lasting until 1 week after the last fraction. See section 5.3.3 regarding this criterion.
• Serious medical comorbidities precluding radiotherapy. These include interstitial lung disease in patients requiring thoracic radiation, Crohn's disease in patients where the gastrointestinal (GI) tract will receive radiotherapy, and connective tissue disorders such as lupus or scleroderma.
• Substantial overlap with a previously treated radiation volume. Prior radiotherapy in general is allowed, as long as the composite plan meets dose constraints herein. For patients treated with radiation previously, similar biological effective dose calculations should be used to equate previous doses to the tolerance doses listed below. All such cases should be discussed with the local and study principal investigators (PIs).
• Current malignant pleural effusion
• Liver metastases located in the "Biliary no fly zone" defined for this trial as common biliary track, cystic duct and distal branches (1 cm) + 5 mm.
• Inability to treat all sites of oligometastatic or oligoprogressive disease
• Maximum size of 5 cm for lesions outside the brain, except:
• Bone metastases over 5 cm may be included, if in the opinion of the local PI it can be treated safely (e.g. rib, scapula, pelvis)
• Any brain metastasis > 3.5 cm in size or a total volume of brain metastases greater than 30 cc is excluded
• Clinical or radiologic evidence of spinal cord compression. Patients can be eligible if surgical resection has been performed
• Patients with spine instability as judged by a Spinal Instability Neoplastic Score (SINS) of >12
• Dominant brain metastasis requiring surgical decompression
• Surgical resection of all metastases (i.e. no lesion available to be treated with SABR)
• Pregnant or breast feeding

Related Conditions & MeSH terms

• Oligometastatic Disease
• Quality of Life
• Toxicity Due to Radiotherapy

Intervention

Radiation:
• Single fraction SABR
Participants randomized to this arm will receive SF SABR Treatment recommendations are as follows: Lung: Greater than 2 cm from mediastinum or brachial plexus or if mandatory OAR constraints are met: 30 Gy in 1 fraction Lung: Within 2 cm of mediastinum or brachial plexus 20 Gy in 1 fraction Bone, Spine, Adrenal, lymph node/soft tissue: 20 Gy in 1 fraction Liver: 30 Gy in 1 fraction Brain: dose as per institutional policy
• Multiple fraction SABR
Participants randomized to this arm will receive MF SABR: Dose/Fractionation are as follows: Lung: Greater than 2 cm from mediastinum or brachial plexus or if mandatory organ-at-risk (OAR) constraints are met: 48 Gy in 4 fractions (12 Gy/#), 54 Gy in 3 fractions (18 Gy/#), daily or every second day Lung: Within 2 cm of mediastinum or brachial plexus 60 Gy in 8 fractions (7.5 Gy/#), 50 Gy in 5 fractions (10 Gy/#), daily Bone: Any bone except spine: 35 Gy in 5 fractions (7 Gy/#), daily Liver: 54 Gy in 3 fractions (18 Gy/#) or 5 fractions (10.8 Gy/#), daily or every second day Spine: 24 Gy in 2 fractions (12 Gy/#) or 35 Gy in 5 fractions (7 Gy/#), daily Adrenal: 40 Gy in 5 fractions (8 Gy/#) or 35 Gy in 5 fractions (7 Gy/#), daily Lymph node/soft tissue: 40 Gy in 5 fractions (8 Gy/#) or 35 Gy in 5 fractions (7 Gy/#), daily Brain - dose per institutional policy for stereotactic lesions (no whole brain RT).

Other:
• QoL reporting alone
Participants randomized to this arm will complete the EQ-5D-5L and FACT-G at baseline and each follow-up visit
• QoL reporting, symptom screen and healthcare provider intervention
Participants randomized to this arm will complete the FACT,G, EQ-5D-5L, radiation-symptom screen and receive healthcare provider-guided intervention based on their symptom reports.

Locations

Country	Name	City	State
Canada	BC Cancer	Kelowna	British Columbia
Canada	BC Cancer	Prince George	British Columbia
Canada	BC Cancer	Surrey	British Columbia
Canada	BC Cancer	Vancouver	British Columbia
Canada	BC Cancer - Victoria	Victoria	British Columbia

Sponsors (4)

Lead Sponsor	Collaborator
British Columbia Cancer Agency	London Regional Cancer Program, Canada, Princess Margaret Hospital, Canada, Tom Baker Cancer Centre

Country where clinical trial is conducted

Canada, 

References & Publications (12)

[Japanese translation of common terminology criteria for adverse events (CTCAE), and instructions and guidelines]. Int J Clin Oncol. 2004 Dec;9 Suppl 3:1-82. No abstract available. Japanese. — View Citation

Basch E, Deal AM, Kris MG, Scher HI, Hudis CA, Sabbatini P, Rogak L, Bennett AV, Dueck AC, Atkinson TM, Chou JF, Dulko D, Sit L, Barz A, Novotny P, Fruscione M, Sloan JA, Schrag D. Symptom Monitoring With Patient-Reported Outcomes During Routine Cancer Treatment: A Randomized Controlled Trial. J Clin Oncol. 2016 Feb 20;34(6):557-65. doi: 10.1200/JCO.2015.63.0830. Epub 2015 Dec 7. Erratum In: J Clin Oncol. 2016 Jun 20;34(18):2198. J Clin Oncol. 2019 Feb 20;37(6):528. — View Citation

Basch E, Reeve BB, Mitchell SA, Clauser SB, Minasian LM, Dueck AC, Mendoza TR, Hay J, Atkinson TM, Abernethy AP, Bruner DW, Cleeland CS, Sloan JA, Chilukuri R, Baumgartner P, Denicoff A, St Germain D, O'Mara AM, Chen A, Kelaghan J, Bennett AV, Sit L, Rogak L, Barz A, Paul DB, Schrag D. Development of the National Cancer Institute's patient-reported outcomes version of the common terminology criteria for adverse events (PRO-CTCAE). J Natl Cancer Inst. 2014 Sep 29;106(9):dju244. doi: 10.1093/jnci/dju244. Print 2014 Sep. — View Citation

Cella DF, Tulsky DS, Gray G, Sarafian B, Linn E, Bonomi A, Silberman M, Yellen SB, Winicour P, Brannon J, et al. The Functional Assessment of Cancer Therapy scale: development and validation of the general measure. J Clin Oncol. 1993 Mar;11(3):570-9. doi: 10.1200/JCO.1993.11.3.570. — View Citation

Cox BW, Spratt DE, Lovelock M, Bilsky MH, Lis E, Ryu S, Sheehan J, Gerszten PC, Chang E, Gibbs I, Soltys S, Sahgal A, Deasy J, Flickinger J, Quader M, Mindea S, Yamada Y. International Spine Radiosurgery Consortium consensus guidelines for target volume definition in spinal stereotactic radiosurgery. Int J Radiat Oncol Biol Phys. 2012 Aug 1;83(5):e597-605. doi: 10.1016/j.ijrobp.2012.03.009. Epub 2012 May 19. — View Citation

Dunne EM, Sahgal A, Lo SS, Bergman A, Kosztyla R, Dea N, Chang EL, Chang UK, Chao ST, Faruqi S, Ghia AJ, Redmond KJ, Soltys SG, Liu MC. International consensus recommendations for target volume delineation specific to sacral metastases and spinal stereotactic body radiation therapy (SBRT). Radiother Oncol. 2020 Apr;145:21-29. doi: 10.1016/j.radonc.2019.11.026. Epub 2019 Dec 23. — View Citation

Hellman S, Weichselbaum RR. Oligometastases. J Clin Oncol. 1995 Jan;13(1):8-10. doi: 10.1200/JCO.1995.13.1.8. No abstract available. — View Citation

Herdman M, Gudex C, Lloyd A, Janssen M, Kind P, Parkin D, Bonsel G, Badia X. Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L). Qual Life Res. 2011 Dec;20(10):1727-36. doi: 10.1007/s11136-011-9903-x. Epub 2011 Apr 9. — View Citation

Nguyen TK, Chin L, Sahgal A, Dagan R, Eppinga W, Guckenberger M, Kim JH, Lo SS, Redmond KJ, Siva S, Stish BJ, Chan R, Lawrence L, Lau A, Tseng CL. International Multi-institutional Patterns of Contouring Practice and Clinical Target Volume Recommendations for Stereotactic Body Radiation Therapy for Non-Spine Bone Metastases. Int J Radiat Oncol Biol Phys. 2022 Feb 1;112(2):351-360. doi: 10.1016/j.ijrobp.2021.09.004. Epub 2021 Sep 9. — View Citation

Olson R, Mathews L, Liu M, Schellenberg D, Mou B, Berrang T, Harrow S, Correa RJM, Bhat V, Pai H, Mohamed I, Miller S, Schneiders F, Laba J, Wilke D, Senthi S, Louie AV, Swaminath A, Chalmers A, Gaede S, Warner A, de Gruijl TD, Allan A, Palma DA. Stereotactic ablative radiotherapy for the comprehensive treatment of 1-3 Oligometastatic tumors (SABR-COMET-3): study protocol for a randomized phase III trial. BMC Cancer. 2020 May 5;20(1):380. doi: 10.1186/s12885-020-06876-4. — View Citation

Patel PH, Palma D, McDonald F, Tree AC. The Dandelion Dilemma Revisited for Oligoprogression: Treat the Whole Lawn or Weed Selectively? Clin Oncol (R Coll Radiol). 2019 Dec;31(12):824-833. doi: 10.1016/j.clon.2019.05.015. Epub 2019 Jun 8. — View Citation

Redmond KJ, Robertson S, Lo SS, Soltys SG, Ryu S, McNutt T, Chao ST, Yamada Y, Ghia A, Chang EL, Sheehan J, Sahgal A. Consensus Contouring Guidelines for Postoperative Stereotactic Body Radiation Therapy for Metastatic Solid Tumor Malignancies to the Spine. Int J Radiat Oncol Biol Phys. 2017 Jan 1;97(1):64-74. doi: 10.1016/j.ijrobp.2016.09.014. Epub 2016 Sep 17. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse events	Occurrences and changes in grade 3 or higher adverse events related to treatment, according to CTCAE v5.0	At 6 weeks, 3 months, 6 months, 12 months, 24 months, 36 months, 48 months, 60 months
Primary	Change in patient-reported quality of life	As measured by the EQ-5D-5L. This questionnaire provides measures for mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. It also includes a numbered scale from 0 to 100 where 100 means the best health one can imagine, and 0 means the worst health one can imagine.	At 6 weeks, 3 months, 6 months, 12 months, 24 months, 36 months, 48 months, 60 months
Secondary	Lesional control rate	Rate is determined based on lesion size post-SABR using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1	At 6 weeks, 3 months, 6 months, 12 months, 24 months, 36 months, 48 months, 60 months
Secondary	Progression-free survival	Time from randomization to disease progression at any site or death	At 6 weeks, 3 months, 6 months, 12 months, 24 months, 36 months, 48 months, 60 months
Secondary	Overall survival	Time from randomization to death from any cause (exploratory)	Approximately at the end of year 5 of follow-up, at study completion
Secondary	Resource utilization	Assessed via patient- and provider-reported hospitalization rates, frequency of emergency department visits, number of patients with systemic or radiation therapy post SABR treatment on trial	At 3 months, 6 months, 12 months, 24 months, 36 months, 48 months, 60 months