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

E

European Organisation for Research and Treatment of Cancer (EORTC)

Status

Not yet enrolling

Conditions

Breast Cancer
Oligometastatic Disease
Prostate Cancer
Colorectal Cancer
NSCLC

Treatments

Radiation: multiple-fraction SBRT
Radiation: single-fraction SBRT

Study type

Interventional

Funder types

NETWORK

Identifiers

NCT06462963
EORTC-2387

Details and patient eligibility

About

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.

Full 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.

Enrollment

302 estimated patients

Sex

All

Volunteers

No Healthy Volunteers

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.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

302 participants in 2 patient groups

single-fraction SBRT
Experimental group
Description:
All lesions to be treated with radical radiotherapy will be treated with single-fraction SBRT, delivered using a dose ranging from 16 Gy to 34 Gy, depending on metastasis location. Acceptable ablative doses are developed in the protocol (see Section 6.4). Radiotherapy treatment will last from one single visit to a few weeks, depending on the number of treated metastases.
Treatment:
Radiation: single-fraction SBRT
multiple-fraction SBRT
Active Comparator group
Description:
All lesions to be treated with radical radiotherapy will be treated with multiple-fraction SBRT.
Treatment:
Radiation: multiple-fraction SBRT

Trial contacts and locations

0

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Central trial contact

EORTC HQ

Data sourced from clinicaltrials.gov

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