Longitudinal Study of Local Ablative Therapy in Oligometastatic Disease

Surgery Clinical Trial

— OLIGO-DK  

Official title:

A National Longitudinal Study of Metastases-directed Local Ablative Therapy for Patients With Oligometastatic Disease - a Combined Interventional and Observational Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06356779
• Other study ID #: H-23066725
• Status: Recruiting
• Phase: N/A
• Start date: April 15, 2024
• Est. completion date: December 31, 2035

Study information

• Verified date: April 2024
• Source: Herlev Hospital
• Contact: Michael RT Laursen, MD
• Phone: +45 3868 9202
• Email: michael.ruben.teindl.laursen[@]regionh.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1200
• Est. completion date: December 31, 2035
• Est. primary completion date: December 31, 2030
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Ablation Techniques
• Metastases
• Neoplasm Metastasis
• Oligometastatic Disease
• Radiotherapy
• Surgery

Intervention

Procedure:
• Local ablative therapy (LAT)
Surgical metastasectomy, stereotactic ablative radiotherapy, thermal ablation, or electroporation to all oligometastatic lesions

Locations

Country	Name	City	State
Denmark	Aalborg University Hospital	Aalborg	Northern Region Of Denmark
Denmark	Aarhus University Hospital	Aarhus	Central Denmark Region
Denmark	Danish Center for Particle Therapy	Aarhus	Central Region Denmark
Denmark	Copenhagen University Hospital Rigshospitalet	Copenhagen	Capital Region Of Denmark
Denmark	Copenhagen University Hospital Herlev and Gentofte	Herlev	Capital Region Of Denmark
Denmark	Gødstrup Hospital	Herning	Central Denmark Region
Denmark	Hillerød Hospital	Hillerød	Capital Region Of Denmark
Denmark	Odense University Hospital	Odense	Southern Denmark Region
Denmark	Zealand University Hospital, Roskilde and Næstved	Roskilde	Zealand Region
Denmark	Sønderborg Hospital	Sønderborg	Southern Denmark Region
Denmark	Vejle Hospital	Vejle	Southern Denmark Region

Sponsors (1)

Lead Sponsor	Collaborator
Gitte Fredberg Persson MD PhD

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to failure of local ablative therapy (LAT) strategy	Defined as time from first day of LAT to progression of disease, locally or metastatically, not amenable to new LAT or progression of disease leading to initiation of or change in systemic treatment	Assessed every 3-6 months for 5 years or life-long
Secondary	Progression-free survival	Defined as time from first day of LAT to disease progression at any site or death	Assessed every 3-6 months for 5 years or life-long
Secondary	Time to widespread progression	Defined as time from first day of LAT to disease progression not amenable to new LAT. Deaths from any cause are censored. Initiation of or change in systemic treatment is ignored	Assessed every 3-6 months for 5 years or life-long
Secondary	Freedom from systemic treatment	Defined as time from first day of LAT to initiation of systemic treatment, change in systemic treatment, or end of systemic treatment due to progression. Change in or end of systemic treatment due to toxicity is ignored	Assessed every 3-6 months for 5 years or life-long
Secondary	Overall survival	Defined as time from first day of first LAT to death from any cause	Assessed every 3-6 months for 5 years or life-long
Secondary	Time to progression	Defined as time from first day of LAT to progression of the disease. Deaths from any cause are censored	Assessed every 3-6 months for 5 years or life-long
Secondary	Time to local progression	Defined as time from first day of LAT to progression within the treated area. In case of doubt or disagreement, the case is reviewed at the local MDT conference. Deaths from any cause are censored	5 years or life-long
Secondary	Local lesion control rate at 1- and 3-years post-local ablative therapy	Fractions of treated lesions which have not locally progressed at 1- and 3-years after local ablative therapy. Analysed per lesion, per patient, per treatment modality and per organ	3 years
Secondary	Time to distant progression	Defined as time from first day of LAT to progression outside the treatment field. Deaths from any cause are censored.	Assessed every 3-6 months for 5 years or life-long
Secondary	Investigator reported grade 3-5 CTCAE (v.5.0) LAT related toxicity	LAT related toxicity is defined as adverse events which are categorized by the local investigator as suspected expected or suspected unexpected due to LAT	2 years
Secondary	Harms	Defined as LAT-related toxicity which occurs or is worsened within 3- months of end-of-treatment (EOT). LAT-related toxicity, which occurs or is worsened after the commencement of the LAT course but before EOT, is also registered as early toxicity.	Actively every 3-months for 2 years