RESOLUTE Trial Aims to Investigate the Value of Adding Local Ablative Treatment to Standard Systemic Treatment for Unresectable Oligometastatic Colorectal Cancer

NCT ID: NCT05862051

Last Updated: 2023-10-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

75 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-12-14

Study Completion Date

2025-06-14

Brief Summary

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This study aims to assess the clinical benefit of local ablative therapy (LAT) following initial standard first-line systemic treatment including the impact on survival, compared to continued standard first-line systemic treatment for oligometastatic colorectal cancer.

Detailed Description

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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.

Conditions

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Colorectal Cancer Oligometastatic Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Local Ablative Therapy

Intervention Type PROCEDURE

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 first-line systemic treatment

Intervention Type PROCEDURE

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.

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.

Group Type PLACEBO_COMPARATOR

Standard first-line systemic treatment

Intervention Type PROCEDURE

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.

Interventions

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Local Ablative Therapy

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).

Intervention Type PROCEDURE

Standard first-line systemic treatment

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.

Intervention Type PROCEDURE

Eligibility Criteria

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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:

1. max of 3 lesions per organ except for the liver and lung
2. max of 5 lesions in the lung
3. no limitation to the number of liver lesions provided they are all amenable to LAT
4. max of 3 involved organs including a lymph node station
5. only one lymph node station involvement is allowed
6. 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
7. 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Walter and Eliza Hall Institute of Medical Research

OTHER

Sponsor Role collaborator

Cancer Council Victoria

OTHER

Sponsor Role collaborator

Australasian Gastro-Intestinal Trials Group

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Border Medical Oncology

Albury, New South Wales, Australia

Site Status RECRUITING

Bendigo Hospital

Bendigo, Victoria, Australia

Site Status RECRUITING

Eastern Health

Box Hill, Victoria, Australia

Site Status RECRUITING

The Northern Hospital

Epping, Victoria, Australia

Site Status NOT_YET_RECRUITING

St Vincent's Hospital Melbourne

Fitzroy, Victoria, Australia

Site Status RECRUITING

Peter MaCallum Cancer Centre

Melbourne, Victoria, Australia

Site Status RECRUITING

Peninsula Health

Rosebud, Victoria, Australia

Site Status NOT_YET_RECRUITING

Western Health

Saint Albans, Victoria, Australia

Site Status RECRUITING

Northeast Health Wangaratta

Wangaratta, Victoria, Australia

Site Status RECRUITING

Countries

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Australia

Central Contacts

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Sukanya Sathyamurthie

Role: CONTACT

+61 2 7208 2719

Louise Christophersen

Role: CONTACT

+61 2 7208 2718

Facility Contacts

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Jacqui Mcburnie

Role: primary

Narelle McPhee

Role: primary

Rachel Wong

Role: primary

Karen Matoga

Role: primary

Nadia Ranieri

Role: primary

Marie Luci

Role: primary

Sally Heath

Role: primary

Stephanie Henderson

Role: primary

Nicole Humphreys

Role: primary

Other Identifiers

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RESOLUTE

Identifier Type: -

Identifier Source: org_study_id

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