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

Study Purpose

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.#46; 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 Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion Criteria

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

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT04498767
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	N/A
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	European Organisation for Research and Treatment of Cancer - EORTC
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Matthias GuckenbergerPiet Ost
Principal Investigator Affiliation	University of ZurichGasthuiszusters Antwerpen - Sint-Augustinus
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Recruiting
Countries	Belgium, France, Germany, Italy, Poland, Switzerland, United Kingdom
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Gynecologic Cancer, Skin Cancer, Head and Neck Cancer, Sarcoma, Renal Cancer, Bladder Cancer, Upper Urinary Tract Carcinoma, Pancreatic Cancer, Hepatobiliary Cancer, Gastric Cancer, Small Bowel Cancer, Esophageal Cancer, Melanoma, Colon Cancer, Oligometastasis

Arms & Interventions

Arms

Active Comparator: Arm 1: Standard of Care + 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). Systemic therapy will be pre-specified based on the standard of care approach for that patient, and it may include cytotoxic, targeted, hormonal, or immunotherapy.

Experimental: Arm 2: Standard of Care + SBRT

The experimental arm consists of SBRT (and standard of care systemic therapy). 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. Patients treated with prior or concomitant systemic therapy are eligible for this study. Use of chemotherapy regimens, targeted therapy or immunotherapy containing potent enhancers of radiation damage (e.g. gemcitabine, doxorubicin) can be postponed or interrupted for a duration of one month after radiation.

Interventions

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.

Radiation: - Palliative RT

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.