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

Primary Purpose

Gynecologic Cancer, Skin Cancer, Head and Neck Cancer

Status
Recruiting
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
Stereotactic body radiotherapy
Palliative RT
Sponsored by
European Organisation for Research and Treatment of Cancer - EORTC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Gynecologic Cancer focused on measuring oligometastatic cancer, Stereotactic body radiotherapy, SBRT

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Universitair Ziekenhuis GentRecruiting
  • Gasthuiszusters Antwerpen - Sint-AugustinusRecruiting
  • Centre Oscar LambretRecruiting
  • Gustave RoussyRecruiting
  • Istituto Europeo di OncologiaRecruiting
  • InselspitalRecruiting
  • UniversitaetsSpital ZurichRecruiting
  • University Hospitals Birmingham NHS Foundation Trust (UHB) - UHB-Queen Elisabeth Medical Centre
  • Royal Marsden Hospital - site: Chelsea, London

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Arm 1: Standard of Care + palliative RT

Arm 2: Standard of Care + SBRT

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Progression-free survival
Disease-specific survival
Time to disease progression
Disease-specific survival is the time interval from the date of randomization to the date of cancer-related death.
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.
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.
Adverse events graded according to the National Cancer Institute Common Terminology Criteria for adverse events (NCI-CTCAE) version 5.0
Health-related quality of life evaluated using self-administered EORTC QLQ-C30 questionnaires
Health-related quality of life evaluated using self-administered EQ-5D-5L questionnaires

Full Information

First Posted
July 30, 2020
Last Updated
April 14, 2023
Sponsor
European Organisation for Research and Treatment of Cancer - EORTC
Collaborators
Anticancer Fund, Belgium, Rising Tide Foundation
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1. Study Identification

Unique Protocol Identification Number
NCT04498767
Brief Title
Stereotactic Body Radiotherapy in Patients With Rare Oligometastatic Cancers (OligoRARE)
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 10, 2021 (Actual)
Primary Completion Date
August 1, 2028 (Anticipated)
Study Completion Date
February 1, 2030 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
European Organisation for Research and Treatment of Cancer - EORTC
Collaborators
Anticancer Fund, Belgium, Rising Tide Foundation

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
Keywords
oligometastatic cancer, Stereotactic body radiotherapy, SBRT

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
200 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm 1: Standard of Care + palliative RT
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Arm 2: Standard of Care + SBRT
Arm Type
Experimental
Arm Description
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.
Intervention Type
Radiation
Intervention Name(s)
Stereotactic body radiotherapy
Other Intervention Name(s)
SBRT
Intervention Description
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.
Intervention Type
Radiation
Intervention Name(s)
Palliative RT
Intervention Description
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).
Primary Outcome Measure Information:
Title
Overall survival
Description
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.
Time Frame
7.5 years from first patient in
Secondary Outcome Measure Information:
Title
Progression-free survival
Time Frame
9 years from first patient in
Title
Disease-specific survival
Time Frame
9 years from first patient in
Title
Time to disease progression
Description
Disease-specific survival is the time interval from the date of randomization to the date of cancer-related death.
Time Frame
9 years from first patient in
Title
Time to development of new metastatic lesions
Description
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.
Time Frame
9 years from first patient in
Title
Time to development of polymetastatic disease
Description
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.
Time Frame
9 years from first patient in
Title
Adverse events graded according to the National Cancer Institute Common Terminology Criteria for adverse events (NCI-CTCAE) version 5.0
Time Frame
9 years from first patient in
Title
Health-related quality of life evaluated using self-administered EORTC QLQ-C30 questionnaires
Time Frame
9 years from first patient in
Title
Health-related quality of life evaluated using self-administered EQ-5D-5L questionnaires
Time Frame
9 years from first patient in

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
EORTC HQ
Phone
+32 2 7744 1611
Email
eortc@eortc.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Matthias Guckenberger
Organizational Affiliation
University of Zurich
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Piet Ost
Organizational Affiliation
Gasthuiszusters Antwerpen - Sint-Augustinus
Official's Role
Principal Investigator
Facility Information:
Facility Name
Universitair Ziekenhuis Gent
City
Gent
ZIP/Postal Code
9000
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pieter Deseyne, MD
First Name & Middle Initial & Last Name & Degree
Pieter Deseyne, MD
Facility Name
Gasthuiszusters Antwerpen - Sint-Augustinus
City
Wilrijk
ZIP/Postal Code
2610
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Piet Ost, MD
First Name & Middle Initial & Last Name & Degree
Piet Ost, MD
Facility Name
Centre Oscar Lambret
City
Lille
ZIP/Postal Code
59020
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
David Pasquier, MD
First Name & Middle Initial & Last Name & Degree
David Pasquier, MD
Facility Name
Gustave Roussy
City
Villejuif
ZIP/Postal Code
94805
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Antonin Levy, MD
First Name & Middle Initial & Last Name & Degree
Antonin Levy, MD
Facility Name
Istituto Europeo di Oncologia
City
Milano
ZIP/Postal Code
20141
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Daniela Alterio, MD
First Name & Middle Initial & Last Name & Degree
Daniela Alterio, MD
Facility Name
Inselspital
City
Bern
ZIP/Postal Code
3010
Country
Switzerland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hossein Hemmatazad, MD
First Name & Middle Initial & Last Name & Degree
Hossein Hemmatazad, MD
Facility Name
UniversitaetsSpital Zurich
City
Zurich
ZIP/Postal Code
8091
Country
Switzerland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Matthias Guckenberger, MD
First Name & Middle Initial & Last Name & Degree
Matthias Guckenberger, MD
Facility Name
University Hospitals Birmingham NHS Foundation Trust (UHB) - UHB-Queen Elisabeth Medical Centre
City
Birmingham
ZIP/Postal Code
B15 2TH
Country
United Kingdom
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jennifer Sherriff, MD
First Name & Middle Initial & Last Name & Degree
Jennifer Sherriff, MD
Facility Name
Royal Marsden Hospital - site: Chelsea, London
City
London
ZIP/Postal Code
SW3 6JJ
Country
United Kingdom
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Shane Zaidi, MD

12. IPD Sharing Statement

Learn more about this trial

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

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