Stereotactic Body Radiotherapy in Patients With Rare Oligometastatic Cancers (OligoRARE)

Pancreatic Cancer Clinical Trial

— OligoRARE  

Official title:

Stereotactic Body Radiotherapy in Addition to Standard of Care Treatment in Patients With Rare Oligometastatic Cancers (OligoRARE): a Randomized, Phase 3, Open-label Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04498767
• Other study ID #: EORTC 1945
• Status: Recruiting
• Phase: N/A
• Start date: June 10, 2021
• Est. completion date: February 1, 2030

Study information

• Verified date: April 2024
• Source: European Organisation for Research and Treatment of Cancer - EORTC
• Contact: EORTC HQ
• Phone: +32 2 7744 1611
• Email: eortc[@]eortc.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a randomized open-label multicentre Phase III superiority study of the effect of adding SBRT to the standard of care treatment on overall survival in patients with rare oligometastatic cancers. Patients will be randomized in a 1:1 ratio between current standard of care treatment vs. standard of care treatment + SBRT to all sites of known metastatic disease. The primary objective of this trial is to assess if the addition of stereotactic body radiotherapy (SBRT) to standard of care treatment improves overall survival (OS) as compared to standard of care treatment alone in patients with rare oligometastatic cancers.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: February 1, 2030
• Est. primary completion date: August 1, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically confirmed malignancy with metastatic disease detected on imaging. Biopsy of metastasis is preferred, but not required.
• Controlled primary tumour, defined as:
• at least 3 months since original tumour treated definitively, with no progression at primary site
• Total number of oligometastases of 1-5 including:
• Brain metastases amenable to radiosurgery or fractionated stereotactic radiotherapy patient who had neurosurgical resection before trial inclusion are allowed and resected brain metastases count to the total number of oligometastases
• All sites of disease can be safely treated based on the judgement of an experienced radiation oncologist
• ECOG score 0-2
• Life expectancy > 6 months
• Age 18 or older
• Before patient randomization, written informed consent must be given according to ICH/GCP, and national/local regulations.

Exclusion Criteria:

• Primary cancer of prostate, breast, lung or colorectal
• Serious medical comorbidities precluding radiotherapy:
• These include interstitial lung disease in patients requiring thoracic radiation, Crohn's disease in patients where the GI tract will receive radiotherapy, or ulcerative colitis where the bowel will receive radiotherapy and connective tissue disorders such as lupus or scleroderma.
• For patients with liver metastases, moderate/severe liver dysfunction (Child Pugh B or C)
• Substantial overlap with a previously treated radiation volume. Prior radiotherapy in general is allowed, as long as the composite plan meets dose constraints herein. For patients treated previously with radiation, biological effective dose calculations should be used to equate previous doses to the tolerance doses listed in the RTQA Guidelines. All such cases should be discussed with one of the study coordinators
• Brain metastases only, without extra-cerebral metastases
• Malignant pleural effusion, malignant ascites, meningeal carcinomatosis and peritoneal carcinomatosis
• Maximum size of 6 cm for lesions outside the brain, except:
• Bone metastases over 5 cm may be included, if in the opinion of the local radiation oncologist it can be treated safely (e.g. rib, scapula, pelvis)
• Clinical or radiologic evidence of symptomatic spinal cord compression. Patients can be eligible if surgical resection has been performed, but the surgical site counts toward the total of up to 3 metastases.
• Metastatic disease that invades any of the following: GI tract (including oesophagus, stomach, small or large bowel), mesenteric lymph nodes, or disseminated skin metastases and lymphangiosis
• Pregnant or breast feeding women
• Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before randomization in the trial

Related Conditions & MeSH terms

• Bladder Cancer
• Colon Cancer
• Esophageal Cancer
• Gastric Cancer
• Gynecologic Cancer
• Head and Neck Cancer
• Hepatobiliary Cancer
• Kidney Neoplasms
• Melanoma
• Oligometastasis
• Pancreatic Cancer
• Renal Cancer
• Sarcoma
• Skin Cancer
• Small Bowel Cancer

Intervention

Radiation:
• Stereotactic body radiotherapy
Each lesion may be treated with 1, 3, or 5 SBRT fractions of 16-24 Gy, 24-33 Gy or 25-40 Gy, respectively, depending on the local practice and size & location of oligometastases. Three-fraction regimens will deliver a fraction every second day, and five-fraction regimens are delivered daily. All treatments must be completed within 2 weeks (10 working days) in order to avoid delays in starting systemic therapy.
• Palliative RT
Radiotherapy for patients in the standard arm should follow the principles of palliative radiotherapy as per the individual institution, with the goal of alleviating symptoms or preventing imminent complications. Recommended dose fractionations in this arm will include 8 Gy in 1 fractions, 20 Gy in 5 fractions, and 30 Gy in 10 fractions. Patients in this arm should not receive stereotactic doses or radiotherapy boosts, unless there is a clearly known clinical benefit (e.g. stereotactic radiation to a new brain metastases when all disease is controlled on systemic therapy).

Locations

Country	Name	City	State
Belgium	Institut Jules Bordet	Anderlecht
Belgium	Universitair Ziekenhuis Gent	Gent
Belgium	Gasthuiszusters Antwerpen - Sint-Augustinus	Wilrijk
France	Centre Oscar Lambret	Lille
France	Gustave Roussy	Villejuif
Germany	Universitaets Krankenhaus Eppendorf - Universitaetsklinikum Hamburg-Eppendorf KE - University Cancer Center	Hamburg	Martinistrasse 52
Italy	Istituto Europeo di Oncologia	Milano
Poland	Maria Sklodowska-Curie Memorial Cancer Centre - Maria Sklodowska-Curie National Research Institute of Oncology	Warsaw
Switzerland	Inselspital	Bern
Switzerland	UniversitaetsSpital Zurich	Zurich
United Kingdom	University Hospitals Birmingham NHS Foundation Trust (UHB) - UHB-Queen Elisabeth Medical Centre	Birmingham
United Kingdom	Royal Marsden Hospital - site: Chelsea, London	London

Sponsors (3)

Lead Sponsor	Collaborator
European Organisation for Research and Treatment of Cancer - EORTC	Anticancer Fund, Belgium, Rising Tide Foundation

Countries where clinical trial is conducted

Belgium,  France,  Germany,  Italy,  Poland,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival	Overall survival is the time interval from the date of randomization to the date of death whatever the cause of death. Patients who are alive are censored at the last date known to be alive.	7.5 years from first patient in
Secondary	Progression-free survival		9 years from first patient in
Secondary	Disease-specific survival		9 years from first patient in
Secondary	Time to disease progression	Disease-specific survival is the time interval from the date of randomization to the date of cancer-related death.	9 years from first patient in
Secondary	Time to development of new metastatic lesions	Time to development of new metastatic lesions is the time interval from the date of randomization to the date of first occurrence of any of the following events: Development new metastatic lesions,; Cancer-related death.	9 years from first patient in
Secondary	Time to development of polymetastatic disease	Time to development of polymetastatic disease is the time interval from the date of randomization to the date of first occurrence of any of the following events: Presence of more than 5 metastases at a specific timepoint during follow-up,; Development of metastases that preclude treatment with SBRT (e.g. due to large size or locating in previously irradiated region where re-irradiation is not possible),; Cancer-related death.	9 years from first patient in
Secondary	Adverse events graded according to the National Cancer Institute Common Terminology Criteria for adverse events (NCI-CTCAE) version 5.0		9 years from first patient in
Secondary	Health-related quality of life evaluated using self-administered EORTC QLQ-C30 questionnaires		9 years from first patient in
Secondary	Health-related quality of life evaluated using self-administered EQ-5D-5L questionnaires		9 years from first patient in