Clinical trial NCT06356779: Longitudinal Study of Local Ablative Therapy in Oligometastatic Disease
Official title: A National Longitudinal Study of Metastases-directed Local Ablative Therapy for Patients With Oligometastatic Disease - a Combined Interventional and Observational Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Oligometastatic Disease
Metastases
Ablation Techniques
Radiotherapy
Stereotactic Radiation
Surgery
Keywords: oligometastatic disease
metastases-directed therapy
metastasectomy
thermal ablation
stereotactic ablative radiotherapy
stereotactic radiosurgery
endpoints
Lead sponsor: Herlev Hospital
Sponsor class: OTHER
First posted: 2024-04-10
Enrollment: 1200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This prospective national multicenter observational and interventional study aims to assess the longitudinal disease trajectory of patients with oligometastatic disease (OMD) who receive local metastasis-directed therapy. Patients with any category of OMD from any non-hematological cancer are eligible for inclusion. Local ablative therapy (LAT) includes surgical metastasectomy, radiotherapy, thermal ablation, and electroporations.

The primary objective is to assess the time to failure of LAT strategy in patients with OMD from any primary cancer treated with all LAT modalities.

Detailed description: Patients with oligometastatic disease (OMD) are often treated with a combination of surgery, stereotactic radiotherapy, thermal ablations, or electroporation, either concurrently or in succession, however, most studies are focused on a single modality. In addition, local differences in the use of local ablative therapy (LAT) in different metastatic sites and diseases exist and may impact outcomes for patients with OMD. OLIGO-DK is designed to address these shortcomings. The aim is to offer LAT with any modality to all patients with OMD from all primary cancer histologies and in all metastatic sites, where it is deemed clinically relevant, within the framework of a national prospective multicenter study, combining both standard and non-standard LAT of OMD in an observational and an interventional cohort, respectively. At the same time, we aim to assess the longitudinal treatment trajectory of oligometastatic patients and create a national network for radiotherapy of oligometastases. Finally, we aim to create a clinically applicable prediction model for patient selection.

The trial is a national, prospective, multicentre trial. Patients with both genuine and induced non-hematological OMD who are receiving metastases-directed local ablative therapy are included, and all LAT modalities of all metastatic sites from all primary cancers are included. The trial will include both an observational cohort and an interventional cohort.

The observational cohort will include patients with OMD who are treated with LAT, which is considered standard-of-care according to national guidelines. The interventional cohort will include patients who are treated with implemented LAT techniques but for indications that are not considered standard-of-care. The final decision on treatment choice is made by the treating physician in consultation with the patient, and the patient may be referred across regional borders for specific treatments. This trial is not on its own designed for the evaluation of novel or experimental LAT techniques, where safety is a primary concern. In these cases, a separate ethical approval protocol is necessary. Patients can still be included in the OLIGO-DK protocol for prospective data collection. In addition, inclusion in this protocol does not impede patients from inclusion in other oligometastatic protocols. Patients are prospectively included, followed, and evaluated by the Centralised Trial Unit and remain included for follow-up until death or patient preference. Due to the nature of oligometastatic disease, patients may receive LAT more than once in the protocol, if the disease is amenable to further local ablative therapy.

The trial will initiate accrual in the Capital Region of Denmark, with subsequent expansion after the first interim analysis. A national OMD MDT conference and a nationwide overview of LAT options will be established during the trial. All departments of oncology, and their associated departments of surgery and interventional radiology performing LAT will be able to include patients.

Eligibility criteria: Inclusion Criteria:

* Histology or cytology proven non-haematological cancer
* Stage IV disease
* ECOG performance status ≤ 2
* Life expectancy \> 6 months
* A baseline scan within 42 days of inclusion (PET-CT or CT or MRI scan) is required, preferably within 28 days for optimal prospective evaluation
* Primary tumor must be controlled, defined by the radiographical response of the primary tumor by systemic or local treatment. If progressing, it is planned to be treated with local ablative therapy (LAT)
* Oligometastatic disease according to the ESTRO-EORTC classification, both de-novo and induced, including oligoprogression
* A maximum of five oligometastases or oligopersistent/oligoprogressive lesions. More than five metastases are allowed in the following cases, 1) location in a defined anatomical entity or 2) location in immediate proximity and as such, cannot be treated separately
* All oligometastatic lesions must be planned for definitive LAT. If all visible/progressive/persistent disease is not treated, the patient cannot be included
* Local ablative therapy must be deemed clinically relevant for the individual patient by the treating team of physicians, or a multidisciplinary team and discussion must be documented in the patient chart
* Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

* Pregnancy
* Diffuse cancer disease, which cannot be locally ablated, i.e., leptomeningeal carcinomatosis, malignant pleural effusions, lymphangitic carcinomatosis, or peritoneal carcinomatosis
* If LAT is deemed unsafe by the MDT (e.g., tumor perforation of hollow organs)

In addition, the patients receiving SBRT to oligometastatic sites should comply with the following criteria.

* The size of the target is limited by the ability to safely deliver locally ablative doses to the metastatic lesions. Generally, an upper limit of 5 cm is recommended
* If the patient has received previous radiotherapy, the combined dose at the radiation site must not exceed the dose constraints according to Appendix 2 - Radiotherapy Recommendations

Primary outcomes:
measure: Time to failure of local ablative therapy (LAT) strategy
timeFrame: Assessed every 3-6 months for 5 years or life-long
Secondary outcomes:
measure: Progression-free survival
timeFrame: Assessed every 3-6 months for 5 years or life-long
measure: Time to widespread progression
timeFrame: Assessed every 3-6 months for 5 years or life-long
measure: Freedom from systemic treatment
timeFrame: Assessed every 3-6 months for 5 years or life-long
measure: Overall survival
timeFrame: Assessed every 3-6 months for 5 years or life-long
measure: Time to progression
timeFrame: Assessed every 3-6 months for 5 years or life-long
measure: Time to local progression
timeFrame: 5 years or life-long
measure: Local lesion control rate at 1- and 3-years post-local ablative therapy
timeFrame: 3 years
measure: Time to distant progression
timeFrame: Assessed every 3-6 months for 5 years or life-long
measure: Investigator reported grade 3-5 CTCAE (v.5.0) LAT related toxicity
timeFrame: 2 years
measure: Harms
timeFrame: Actively every 3-months for 2 years
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Copenhagen University Hospital Rigshospitalet
state: Capital Region Of Denmark
city: Herlev
country: Denmark
facility: Copenhagen University Hospital Herlev and Gentofte
state: Capital Region Of Denmark
city: Hillerød
country: Denmark
facility: Hillerød Hospital
state: Capital Region Of Denmark
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
state: Central Denmark Region
city: Herning
country: Denmark
facility: Gødstrup Hospital
state: Central Denmark Region
city: Aarhus
country: Denmark
facility: Danish Center for Particle Therapy
state: Central Region Denmark
city: Aalborg
country: Denmark
facility: Aalborg University Hospital
state: Northern Region Of Denmark
city: Odense
country: Denmark
facility: Odense University Hospital
state: Southern Denmark Region
city: Sønderborg
country: Denmark
facility: Sønderborg Hospital
state: Southern Denmark Region
city: Vejle
country: Denmark
facility: Vejle Hospital
state: Southern Denmark Region
city: Roskilde
country: Denmark
facility: Zealand University Hospital, Roskilde and Næstved
state: Zealand Region
Study officials:
affiliation: Copenhagen University Hospital Herlev and Gentofte
name: Gitte F Persson, MD PhD
role: STUDY_CHAIR
affiliation: Copenhagen University Hospital Herlev and Gentofte
name: Michael RT Laursen, MD
role: PRINCIPAL_INVESTIGATOR
References: