OligoCare TwiCs (Trials Within Cohorts) Trial Comparing Acute Toxicity in Single-fraction vs Multiple-fraction SBRT for Metastasis-directed Treatment (SPRINT)

Breast Cancer Clinical Trial

— SPRINT  

Official title:

OligoCare TwiCs (Trials Within Cohorts) Trial Comparing Acute Toxicity in Single-fraction vs Multiple-fraction SBRT for Metastasis-directed Treatment (SPRINT)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06462963
• Other study ID #: EORTC-2387
• Status: Not yet recruiting
• Phase: N/A
• Start date: December 15, 2024
• Est. completion date: November 15, 2028

Study information

• Verified date: June 2024
• Source: European Organisation for Research and Treatment of Cancer - EORTC
• Contact: EORTC HQ
• Phone: +32 2 774 16 11
• Email: eortc[@]eortc.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this clinical trial is to evaluate single-fraction metastases-directed SBRT in the broader radiation oncology community and to compare its safety and efficacy profile with the current Standard of Care (SoC) of multiple-fraction SBRT in patients with oligometastatic disease of primary breast, prostate, NSCLC and colorectal cancer having all lesions that will be treated with radical radiotherapy amenable to single-fraction SBRT.

The main question/hypothesis this clinical trial aims to answer is:

• Single-fraction SBRT has comparable outcomes as those obtained with multiple fraction SBRT, both in terms of safety and efficacy.

Patients from the OligoCare cohort will be randomized to receive either single-fraction SBRT or the current SoC of multiple-fraction SBRT.

Description:

As a consequence of improved survival of metastatic cancer patients due to more effective systemic therapy, focused radiotherapy in the form of stereotactic body radiotherapy (SBRT) has become a standard of care in many clinical situations to achieve durable symptom and / or metastasis control: treatment of brain metastases, of painful bone or spinal metastases and especially as local treatment in a multimodality treatment strategy for oligometastatic disease. These indications are supported by international practice guidelines, e.g. ESMO guidelines for NSCLC and colorectal cancer; and NCCN guidelines for NSCLC, prostate cancer, renal cell cancer, colorectal cancer and sarcoma.

However, despite the universal use of SBRT in the local treatment of oligometastases, the level of evidence supporting stereotactic radiotherapy is low, apart from few small prospective clinical trials showing a very favourable toxicity profile of SBRT and promising efficacy data. In this context, the OligoCare research project, a prospective observational cohort study, has been developed within the E²-RADIatE platform. The aim of this project is to collect real-world data on SBRT treatment of patients with oligometastic disease of primary breast, prostate, lung and colorectal cancer, with no limit on the maximum number of treated metastases.

Yet, the local treatment of multiple metastases poses several challenges. One of them is the integration of local metastases-directed SBRT into a systemic treatment strategy: in an interim analysis of the OligoCare cohort, almost all patients were treated with fractionated SBRT and the median number of SBRT fractions was 5. This would result in a total of 50 SBRT fractions in a patient with 10 metastases. Considering that several drugs are paused before and after SBRT, the systemic therapy free interval could last for almost 2 months, which one could consider as unacceptably long in metastatic cancer patients.

One solution to this problem would be the delivery of radiotherapy in a smaller number of SBRT fractions, preferably as single-fraction SBRT. Single-fraction SBRT has been described since the 90's for treatment of liver metastases, lung metastases or vertebral metastases. A recent randomized phase II trial compared multiple-fraction vs single-fraction SBRT for pulmonary oligometastases (n=90) and did not observe differences in toxicity or any oncological outcome parameter.

Nevertheless, single-fraction SBRT still lacks adoption in the radiation oncology community. Likely reasons are the experience of single-fraction SBRT restricted to small, highly specialized centers, the small number of patients treated with single-fraction SBRT in the literature and the concerns of potentially increased toxicity and / or decreased efficacy.

There is consequently a strong rationale to implement and evaluate single-fraction metastases-directed SBRT in the broader radiation oncology community and to compare its safety and efficacy profile with the current SoC of multiple-fraction SBRT.

This question will be addressed in the current Trials within Cohorts (TwiCs) study, in which patients from the OligoCare cohort will be randomized to receive either single-fraction SBRT or the current SoC of multiple-fraction SBRT. The main hypothesis is that single-fraction SBRT has comparable outcomes as those obtained with multiple fraction SBRT, both in terms of safety and efficacy.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 302
• Est. completion date: November 15, 2028
• Est. primary completion date: November 15, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Patient is part of the RP1822-OligoCare. As in OligoCare, ALL active cancer lesions (loco-regional primary and all oligometastases) were or will be treated with radical intent (surgery or radiotherapy).

• All lesions that will be treated with radical radiotherapy have to be amenable to single-fraction SBRT. Concurrent systemic treatment is allowed.

• Written informed consent must be given according to ICH/GCP, and national/local regulations. Patients will be consented in a step-wise approach.

Step 1 [both control and experimental arms]: patients will need to consent to be included and evaluated in E²-RADIatE (that includes the non-interventional OligoCare prospective registry cohort) and to potentially be randomized to future sub-studies for which they are eligible; no further consent will be sought if they are randomized to the SoC (control) arm; Step 2 [experimental arm only]: if eligible for the current sub-study and randomized to receive single-fraction SBRT, patients will need to consent to receiving the experimental treatment.

Exclusion Criteria:

All targeted lesion judged by the treating physician to be associated with risks for severe toxicity following single-fraction SBRT. The following lesions are systematically excluded:

• Pulmonary metastases within 1 cm of proximal bronchial tree, esophagus or brachial plexus

• Metastases within < 5 mm of any hollow GI structure: esophagus, stomach, small bowel, large bowel

• Metastases within < 5 mm of the spinal cord, the cauda equina or the brachial plexus

• Metastases > 5 cm in largest diameter.

Related Conditions & MeSH terms

• Breast Cancer
• Colorectal Cancer
• Colorectal Neoplasms
• NSCLC
• Oligometastatic Disease
• Prostate Cancer

Intervention

Radiation:
• single-fraction SBRT
Single-fraction SBRT (Stereotactic Body Radiation Therapy) is a precise form of radiation therapy that delivers a high dose of radiation in a single treatment session to a targeted area, often used for treating small, well-defined tumors. This approach minimizes exposure to surrounding healthy tissues while effectively treating the tumor.
• multiple-fraction SBRT
Multiple-fraction SBRT (Stereotactic Body Radiation Therapy) is a precise form of radiation therapy that delivers high doses of radiation over several treatment sessions to a targeted area, typically used for treating small, well-defined tumors. This method helps to further protect surrounding healthy tissues by spreading the total radiation dose over multiple sessions.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
European Organisation for Research and Treatment of Cancer - EORTC

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Health-related Quality of life (HRQoL)	The magnitude of change in HRQoL in terms of physical functioning from EORTC QLQ-C30.	4.5 years from first patient in
Other	Health-related Quality of life (HRQoL)	The magnitude of change in HRQoL in terms of pain/discomfort from EQ5D-5L questionnaires.	4.5 years from first patient in
Other	Economic impact of radiation treatment	To document the health economic impact of the two treatments by collecting Use of resources questionnaires during radiation treatment and during follow up.	4.5 years from first patient in
Primary	Grade 3+ SBRT-related toxicity	The cumulative incidence of grade 3+ SBRT-related toxicity within 12 months following treatment with radical radiotherapy. This study will use the International Common Terminology Criteria for Adverse Events (CTCAE), version 5.0, for adverse event reporting.	within 12 months following treatment with radical radiotherapy.
Secondary	Progression free survival (PFS)	defined as the time from the date of randomization to the date of first progression (local, regional or distant) as per local assessment or death.	4.5 years from first patient in
Secondary	Overall survival (OS)	defined as the time from the date of randomization to the date of death from any cause.	4.5 years from first patient in
Secondary	Local control (LC)	defined as freedom from local metastasis (inside the PTV or prior treated field).	4.5 years from first patient in
Secondary	Pattern of progression of primary disease and metastases	Pattern of progression of primary disease and metastases includes local, regional and/or distant progression or recurrence.	4.5 years from first patient in