Longitudinal Study of Local Ablative Therapy in Oligometastatic Disease (OLIGO-DK)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Surgery; Oligometastatic Disease; Radiotherapy; Metastases; Stereotactic Radiation; Ablation Techniques
• Intervention / Treatment: Procedure: Local ablative therapy (LAT)

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.

• Study Type: Interventional
• Enrollment (Estimated): 1200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Michael RT Laursen, MD; Phone Number: +45 3868 9202; Email: michael.ruben.teindl.laursen@regionh.dk
• Study Contact Backup: Name: Gitte F Persson; Phone Number: +453868 9299; Email: Gitte.Persson@regionh.dk

Study Locations

• Denmark
  • Capital Region Of Denmark
    • Copenhagen, Capital Region Of Denmark, Denmark, 2100
      • Not yet recruiting
      • Copenhagen University Hospital Rigshospitalet
      • Contact: Mette Pøhl, MD PhD
      • Principal Investigator: Mette Pøhl, MD PhD
      • Sub-Investigator: Maja Maraldo, MD PhD
      • Sub-Investigator: Morten Suppli, MD PhD
      • Sub-Investigator: Rene H Petersen, MD PhD
      • Sub-Investigator: Hans-Christian Pommergaard, MD PhD
      • Sub-Investigator: Søren Møller, MD PhD
      • Sub-Investigator: Michael Achiam, MD PhD
      • Sub-Investigator: Mikkel Rosendahl, MD PhD
    • Herlev, Capital Region Of Denmark, Denmark, 2730
      • Recruiting
      • Copenhagen University Hospital Herlev and Gentofte
      • Contact: Michael RT Laursen, MD; Phone Number: +453868 9202; Email: michael.ruben.teindl.laursen@regionh.dk
      • Sub-Investigator: Mette Felter, MD PhD
      • Principal Investigator: Henriette Lindberg, MD PhD
      • Sub-Investigator: Eva Serup-Hansen, MD PhD
      • Sub-Investigator: Sebastian Krog, MD
      • Sub-Investigator: Jesper Palshof, MD PhD
      • Sub-Investigator: Bodil Engelmann, MD PhD
      • Sub-Investigator: Eva Ellebæk, MD PhD
      • Sub-Investigator: Lisbet Hölmich, MD PhD
    • Hillerød, Capital Region Of Denmark, Denmark, 3400
      • Not yet recruiting
      • Hillerød Hospital
      • Contact: Maria Lendorf
      • Principal Investigator: Maria Lendorf, MD PD
  • Central Denmark Region
    • Aarhus, Central Denmark Region, Denmark, 8200
      • Not yet recruiting
      • Aarhus University Hospital
      • Contact: Mette Marie Fode, MD PhD; Email: mettfode@rm.dk
      • Principal Investigator: Mette Marie Fode, MD PhD
      • Sub-Investigator: Azza Khalil, MD PhD
      • Sub-Investigator: Thomas Decker Christensen, MD PhD
      • Sub-Investigator: Ole Graumann, MD PhD
      • Sub-Investigator: Jørgen Bjerggaard Jensen, MD PhD
    • Herning, Central Denmark Region, Denmark, 7400
      • Not yet recruiting
      • Gødstrup Hospital
      • Contact: Trine Øllegaard
      • Principal Investigator: Trine Øllegaard, MD PhD
  • Central Region Denmark
    • Aarhus, Central Region Denmark, Denmark, 8200
      • Not yet recruiting
      • Danish Center for Particle Therapy
      • Contact: Britte Weber, MD PhD
      • Principal Investigator: Britta Weber, MD PhD
  • Northern Region Of Denmark
    • Aalborg, Northern Region Of Denmark, Denmark, 9000
      • Not yet recruiting
      • Aalborg University Hospital
      • Contact: Jimmy Søndergaard, MD PhD
      • Contact: Laurids Ø Poulsen, MD PhD
      • Principal Investigator: Jimmi Søndergaard, MD PhD
      • Sub-Investigator: Laurids Ø Poulsen, MD PhD
      • Sub-Investigator: Hella Sand, MSc
  • Southern Denmark Region
    • Odense, Southern Denmark Region, Denmark, 5000
      • Not yet recruiting
      • Odense University Hospital
      • Contact: Tine Schytte, MD PhD
      • Principal Investigator: Tine Schytte, MD PhD
      • Sub-Investigator: Jørgen Johansen, MD PhD
      • Sub-Investigator: Christina Nyborg, MD PhD
    • Sønderborg, Southern Denmark Region, Denmark, 6400
      • Not yet recruiting
      • Sønderborg Hospital
    • Vejle, Southern Denmark Region, Denmark, 7100
      • Not yet recruiting
      • Vejle Hospital
      • Contact: Charlotte Kristiansen, MD
      • Principal Investigator: Charlotte Kristiansen, MD
      • Sub-Investigator: Lars Fokdal, MD PhD
      • Sub-Investigator: Lise Bentzen, MD PhD
  • Zealand Region
    • Roskilde, Zealand Region, Denmark, 4000
      • Not yet recruiting
      • Zealand University Hospital, Roskilde and Næstved
      • Contact: Julie Gehl, MD DMSc
      • Principal Investigator: Julie Gehl, MD DMSc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Local ablative therapy; Discussion at multidisciplinary team conferences Lesion-specific treatment plan with allocation to; surgical metastasectomy; stereotactic radiotherapy; thermal ablation; electroporation	Procedure: Local ablative therapy (LAT); Surgical metastasectomy, stereotactic ablative radiotherapy, thermal ablation, or electroporation to all oligometastatic lesions; Other Names: Metastases-directed therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Gitte Fredberg Persson MD PhD
• Investigators: Study Chair: Gitte F Persson, MD PhD, Copenhagen University Hospital Herlev and Gentofte; Principal Investigator: Michael RT Laursen, MD, Copenhagen University Hospital Herlev and Gentofte

Study record dates

Study Major Dates

• Study Start (Actual): April 15, 2024
• Primary Completion (Estimated): December 31, 2030
• Study Completion (Estimated): December 31, 2035

Study Registration Dates

• First Submitted: March 25, 2024
• First Submitted That Met QC Criteria: April 4, 2024
• First Posted (Actual): April 10, 2024

Study Record Updates

• Last Update Posted (Actual): April 16, 2024
• Last Update Submitted That Met QC Criteria: April 15, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: stereotactic radiosurgery; thermal ablation; metastasectomy; oligometastatic disease; stereotactic ablative radiotherapy; metastases-directed therapy; endpoints
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Neoplasm Metastasis
• Other Study ID Numbers: H-23066725

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Disease specific individual participant data will be available to the Danish Multidisciplinary Cancer Groups.

Modality specific individual participant data will be available for separate analysis.

• IPD Sharing Time Frame: The study protocol and the first draft of the SAP will be shared and available after the publication of the protocol article.
• IPD Sharing Access Criteria: No specific access criteria
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No