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

Australasian Gastro-Intestinal Trials Group

Status: Enrolling

Conditions: Oligometastatic Disease; Colorectal Cancer

Treatments: Procedure: Local Ablative Therapy; Procedure: Standard first-line systemic treatment

Study type: Interventional

Funder types: Other; NETWORK

Identifiers

NCT05862051

RESOLUTE

Details and patient eligibility

About

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.

Full 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.

Enrollment: 75 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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75 participants in 2 patient groups, including a placebo group

Local ablative therapies (LAT) arm

Experimental group

Description:

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.

Treatment:

Procedure: Local Ablative Therapy

Procedure: Standard first-line systemic treatment

Control arm

Placebo Comparator group

Description:

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.

Treatment:

Procedure: Standard first-line systemic treatment