RESOLUTE Trial Aims to Investigate the Value of Adding Local Ablative Treatment to Standard Systemic Treatment for Unresectable Oligometastatic Colorectal Cancer (RESOLUTE)
Randomised Phase II Trial to Evaluate Progression-Free Survival in Integrating Local Ablative Therapy With First-Line Systemic Treatment for Unresectable Oligometastatic Colorectal Cancer
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Who is this study for:
Adults with unresectable oligo-metastatic colorectal who have demonstrated treatment benefit (partial response or stable disease as per RECIST criteria) after 3-4 months of standard first-line systemic treatment.
Study details
Participants will be randomly allocated to either a LAT arm, who will receive metastasis-directed LAT such as radiotherapy or thermal ablation following initial standard first-line systemic treatment, or a control arm who will receive continued first-line systemic treatment alone. Those receiving LAT will return to systemic treatment 16 weeks post-randomisation. Information on progression-free survival and treatment outcomes will be collected.
Data from this study will inform investigators of the potential benefit of local ablative therapy in the therapeutic setting for metastatic colorectal cancer.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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New South Wales
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Albury, New South Wales, Australia, 2640
- Border Medical Oncology
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Victoria
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Bendigo, Victoria, Australia, 3550
- Bendigo Hospital
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Box Hill, Victoria, Australia, 3128
- Eastern Health
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Epping, Victoria, Australia, 3076
- The Northern Hospital
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Fitzroy, Victoria, Australia, 3065
- St Vincent's Hospital Melbourne
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Geelong, Victoria, Australia, 3220
- Barwon Health
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Melbourne, Victoria, Australia, 3000
- Peter MaCallum Cancer Centre
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Saint Albans, Victoria, Australia, 3021
- Western Health
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Wangaratta, Victoria, Australia, 3677
- Northeast Health Wangaratta
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Metastatic colorectal adenocarcinoma that is not amenable to potentially oncological curative surgery alone.
- Primary tumour must be controlled if the primary is intact, with no evidence of progression at primary site prior to study entry
- Imaging demonstrating ongoing treatment benefit (partial response or stable disease as per RECIST criteria) after 3-4 months of standard first-line systemic treatment.
At least one metastatic lesion detected on CT +/- FDG-PET scan prior to first line systemic treatment AND on screening FDG-PET and CT scans, meeting the following criteria:
- max of 3 lesions per organ except for the liver and lung
- max of 5 lesions in the lung
- no limitation to the number of liver lesions provided they are all amenable to LAT
- max of 3 involved organs including a lymph node station
- only one lymph node station involvement is allowed
- for patients with liver metastases, a quadruple phase contrast enhanced CT or MRI liver is required to fully stage the liver; this can be performed prior to or within 4 weeks of commencing first line systemic treatment
- staging FDG-PET scan is encouraged and can be performed prior to or within 4 weeks of commencing first line systemic treatment
- All lesions can be safely treated by LAT as determined by multidisciplinary team meeting.
Exclusion Criteria:
- Deficient mismatch repair (dMMR) or microsatellite instability-high (MSI-high) tumour
- BRAFV600E mutated tumour
- Concurrent or previous other malignancy within 2 years of study entry, except curatively treated basal or squamous cell skin cancer, prostate intraepithelial neoplasm, carcinoma in-situ of the cervix, Bowen's disease or prostate cancer with a Gleason score ≤6.
- Presence of brain, peritoneal, omental or ovarian metastases
- Malignant pleural effusion or ascites.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
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Experimental: Local ablative therapies (LAT) arm
A maximum of three Local ablative therapy (LAT) modalities can be administered for each participant, with a maximum of 2 modalities per organ, provided all LAT can be delivered within 12 weeks and participant can safely resume systemic treatment within 16 weeks from randomisation. After completing LAT, participant is to resume a further two to three months of first-line systemic treatment to a total of 6 months (including the initial 3-4 months of treatment). For patients receiving a doublet or triplet regimen, treatment may be de-escalated to maintenance fluoropyrimidine +/- biologics or anti-EGFR monotherapy at any point after trial entry at clinician discretion. The treating clinician may choose to discontinue systemic treatment following LAT for patients who have experienced prior intolerable toxicity. |
LAT modalities allowed include surgical resection, stereotactic radiotherapy (SRT), laparoscopic or percutaneous thermal ablation [radiofrequency ablation (RFA) or microwave ablation (MWA)].
The LAT modalities will be delivered by specialists in the field (surgeons, radiation oncologists and/or interventional radiologists).
The precise mode of delivery and number of times the LAT modality is delivered is case-dependent and is determined at a multi-disciplinary meeting (MDM).
Standard of care as determined by the treating clinician.
The following standard chemotherapy regimens are allowed: single agent fluoropyrimidine, CAPOX, FOLFOX, FOLFIRI, CAPIRI or FOLFOXIRI.
Treatment with a biologic is allowed including bevacizumab or an anti-EGFR antibody (cetuximab or panitumumab).
For patients receiving a doublet or triplet regimen, treatment may be de-escalated to maintenance fluoropyrimidine +/- biologics or anti-EGFR monotherapy at any point after trial entry at clinician discretion.
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Placebo Comparator: Control arm
The first-line systemic treatment will be standard of care as determined by the treating clinician.
The following standard chemotherapy regimens are allowed: single agent fluoropyrimidine, CAPOX, FOLFOX, FOLFIRI, CAPIRI or FOLFOXIRI.
Treatment with a biologic is allowed including bevacizumab or an anti-EGFR antibody (cetuximab or panitumumab).
For patients receiving a doublet or triplet regimen, treatment may be de-escalated to maintenance fluoropyrimidine +/- biologics or anti-EGFR monotherapy at any point after trial entry at clinician discretion.
|
Standard of care as determined by the treating clinician.
The following standard chemotherapy regimens are allowed: single agent fluoropyrimidine, CAPOX, FOLFOX, FOLFIRI, CAPIRI or FOLFOXIRI.
Treatment with a biologic is allowed including bevacizumab or an anti-EGFR antibody (cetuximab or panitumumab).
For patients receiving a doublet or triplet regimen, treatment may be de-escalated to maintenance fluoropyrimidine +/- biologics or anti-EGFR monotherapy at any point after trial entry at clinician discretion.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Progression free survival (PFS)
Time Frame: 12 Months from randomisation
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To compare the efficacy of metastasis-directed LAT following initial standard first-line systemic treatment vs continued first-line systemic treatment alone, as measured by Progression-Free Survival (PFS)
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12 Months from randomisation
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Overall survival
Time Frame: 12 Months from randomisation and through study completion, an average of 1 year
|
To compare the efficacy of LAT following initial standard first-line systemic treatment, compared to continued first-line systemic treatment alone, as measured by Overall Survival (OS)
|
12 Months from randomisation and through study completion, an average of 1 year
|
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Efficacy of local ablative therapy
Time Frame: 12 Months from randomisation and through study completion, an average of 1 year
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To compare the efficacy of LAT following initial standard first-line systemic treatment, compared to continued first-line systemic treatment alone, on:
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12 Months from randomisation and through study completion, an average of 1 year
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Time to progression following local ablative therapy
Time Frame: Through study completion, an average of 1 year
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To assess the time to progression of LAT treated lesions.
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Through study completion, an average of 1 year
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Systemic treatment-free interval
Time Frame: Through study completion, an average of 1 year
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To compare systemic treatment-free interval between the two treatment groups.
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Through study completion, an average of 1 year
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Rate of high-grade toxicities
Time Frame: Through study completion, an average of 1 year
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To assess and compare rate of high-grade (Grade 3-5) toxicities between the two treatment groups.
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Through study completion, an average of 1 year
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Quality of life measure
Time Frame: Through study completion, an average of 1 year
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To compare quality of life measures between the two treatment groups using patient questionnaire - The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) using the 4-point ordinal scale (not at all, a little, quite a bit and very much)
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Through study completion, an average of 1 year
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Overall survival
Time Frame: Through study completion, an average of 1 year
|
To assess the potential of serial circulating tumour DNA as a prognostic and predictive marker of benefit to LAT treatment. To create a virtual biobank of archival tumour tissue (primary +/- metastases) to support future translational studies of tissue biomarkers that could enable the identification of the oligometastatic phenotype and therefore the patients who are most likely to benefit from LAT. Correlate CT and FDG-PET radiomic metrics with clinical outcome. To examine outcomes relative to a synthetic real-world control arm from the TRACC clinical registry in order to estimate the external validity of study results. |
Through study completion, an average of 1 year
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Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- RESOLUTE
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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