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COLLISION RELAPSE Trial

Primary Purpose

Colorectal Cancer, Liver Metastases, Liver Metastasis Colon Cancer

Status
Recruiting
Phase
Phase 3
Locations
Netherlands
Study Type
Interventional
Intervention
Neoadjuvant systemic therapy (CAPOX+/-B FOLFOX+/-B FOLFIRI+/-B)
Repeat local treatment
Sponsored by
Amsterdam UMC, location VUmc
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Colorectal Cancer

Eligibility Criteria

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

Inclusion criteria Age >18 years Good performance status (ECOG 0-2 // ASA 1-3) Histological documentation of primary colorectal tumor Local treatment performed for initial CRLM New recurrence ≤12 months ≥1 locally treatable CRLM (resectable* and/or ablatable) Total number of new CRLM ≤5 Chemo-naïve or history of response to CAPOX/FOLFOX/FOLRIRI Life expectancy of at least 12 weeks Adequate bone marrow, liver and renal function Written informed consent Exclusion criteria Extrahepatic disease MSI/dMMR Radical local treatment unfeasible or unsafe (e.g. insufficient future liver volume) Compromised liver function (e.g. signs of portal hypertension, INR > 1,5 without use of anticoagulants, ascites) Uncontrolled infections (> grade 2 NCI-CTC version 3.0) Pregnant or breast-feeding subjects Immuno- or chemotherapy ≤ 6 weeks prior to the randomization Severe allergy to contrast media not controlled with premedication Substance abuse, medical, psychological or social conditions that may interfere with the subject's participation in the study or evaluation of the study results ECOG = Eastern Cooperative Oncology Group, ASA = American Society of Anesthesiologists, MSI = Microsatellite instability, dMMR = deficient mismatch repair * Resection for resectable lesions considered possible obtaining negative resection margins (R0) and preserving adequate liver reserve

Sites / Locations

  • Amsterdam UMCRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Upfront repeat local treatment

Neoadjuvant systemic therapy followed by repeat local treatment

Arm Description

Outcomes

Primary Outcome Measures

Overall survival (OS) per patient
Primary objective is to compare overall survival (OS) in both study arms, counting from the date of randomization to the date of death of the patient or to the last day of follow-up (censored).

Secondary Outcome Measures

Distant progression-free survival (DPFS) per patient
Distant progression free survival (DPFS; per patient analysis): Overall DPFS is defined as the time from randomization to the time of disease progression (according to the RECIST 1.1 guideline) or cancer related death (events), death related to other causes is considered a competing risk
Local tumor progression-free survival (LTPFS) per patient and per tumor treated
Local tumor progression free survival (LTPFS; per tumor and per patient analysis): Overall LTPFS is defined as the time from randomization to the time of local disease progression, new metastases (events), censoring the date of death from any cause (competing risk), completion ablations performed within 6 weeks for residual tumor are not considered events for the local tumor progression analysis
Systemic therapy related toxicity per patient following neoadjuvant systemic therapy
Systemic therapy related toxicity is graded from 1 to 5 according to the CTCAE version 5.0
Procedural morbidity and mortality per patient following repeat local treatment
Procedural morbidity and mortality are graded from I to V according to the standard classification of surgical complications
Length of hospital stay per patient following repeat local treatment
In days
Assessment of pain per patient
- Pain assessment using visual analogue scale questionnaires (VAS; per procedure analysis: Assessed prior to, directly after and every three months after local treatment;
Quality of life (QoL) per patient
- To determine quality of life in both treatment arms. Quality of life assessment using EORCT QLQ-C30, EQ-5D, and PRODISQ questionnaires (per procedure analysis): Assessed prior to, and every three months after local treatment, assessed prior to, during and after neoadjuvant systemic therapy
Quality-adjusted life years (QALY) per patient
- Quality-adjusted life years (QALY) per treatment arm (per patient analysis).
Cost-effectiveness ratio (ICER)
- Direct and indirect total costs of care per treatment arm, and incremental cost-effectiveness ratio (ICER)

Full Information

First Posted
April 26, 2023
Last Updated
May 5, 2023
Sponsor
Amsterdam UMC, location VUmc
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1. Study Identification

Unique Protocol Identification Number
NCT05861505
Brief Title
COLLISION RELAPSE Trial
Official Title
COLLISION RELAPSE Trial - Recurrent Colorectal Liver Metastases: Repeat Local Treatment +/- Neoadjuvant Systemic Therapy - a Phase III Prospective Randomized Controlled Trial
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 24, 2023 (Actual)
Primary Completion Date
May 1, 2027 (Anticipated)
Study Completion Date
May 1, 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Amsterdam UMC, location VUmc

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The primary objective is to demonstrate superiority of neoadjuvant systemic therapy followed by repeat local treatment as compared to upfront repeat local treatment in patients with at least one locally treatable recurrent CRLM in the absence of extrahepatic disease.
Detailed Description
Study design: The COLLISION RELAPSE trial is a prospective multicenter phase III randomized controlled trial. The primary conducting center will be the Amsterdam UMC (Amsterdam, the Netherlands). We hypothesize that neoadjuvant systemic therapy followed by repeat local treatment is superior to upfront repeat local treatment for the selected patient groups in terms of the primary objective (OS). The Cox proportional hazards model (1-sided; superiority) and the PASKWIL criteria for adjuvant treatment for the benefit of OS from the Dutch Society of Medical Oncology are used for the sample size calculations. A total number of 360 patients will be randomized (NR) into one of two arms: arm A (control group) upfront repeat local treatment (n=180) and arm B (intervention group) 12 weeks of neoadjuvant systemic therapy followed by repeat local treatment (n=180). Study population: Patients with a maximum of 5 recurrent new locally treatable CRLM within 12 months after initial curative intent local treatment of CRLM, no extrahepatic disease, and a good performance status (ECOG 0-2) are considered eligible. Both chemo-naïve patients and patients who did not progress on either oxaliplatin or irinotecan chemotherapy prior to the initial local treatment are eligible for inclusion. Eligible patients will be stratified before randomization into two groups depending on the interval between initial local treatment and first detection of recurrent CRLM: recurrence within 6 months and recurrence between 6 and 12 months, RAS/BRAF mutation vs RAS/BRAF wildtype, prognostic risk score (low vs high risk, clinical risk score Fong et al. (83)) and previous chemotherapy versus no previous chemotherapy. Intervention: Eligible patients will be randomized into one of two arms: arm A (control group) upfront repeat local treatment and arm B (intervention group) 12 weeks of neoadjuvant systemic therapy followed by repeat local treatment. Patients in arm B will receive maximum 4 cycles of CAPOX or 6 cycles of FOLFOX/FOLFIRI +/- bevacizumab regardless of the location of primary tumor or RAS/BRAF mutation. Choice of repeat local treatment is to the discretion of the local investigator, and may be selected on a per patient basis.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer, Liver Metastases, Liver Metastasis Colon Cancer, Chemotherapy Effect, Surgery, Recurrence

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
360 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Upfront repeat local treatment
Arm Type
Active Comparator
Arm Title
Neoadjuvant systemic therapy followed by repeat local treatment
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Neoadjuvant systemic therapy (CAPOX+/-B FOLFOX+/-B FOLFIRI+/-B)
Intervention Description
Standard first line systemic treatment: CAPOX+/-B FOLFOX+/-B FOLFIRI+/-B CAPOX 4x (12 weeks) FOLFOX/FOLFIRI 6x (12 weeks) Maximum 4 cycles of CAPOX or 6 cycles of FOLFOX/FOLFIRI +/- bevacizumab regardless of the location of primary tumor or RAS/BRAF mutation
Intervention Type
Other
Intervention Name(s)
Repeat local treatment
Intervention Description
Choice of repeat local treatment is to the discretion of the local investigator, and may be selected on a per patient basis. The safety, feasibility and preferred type of surgical resection(s) is at the discretion of the liver surgeon (whether or not combined with thermal ablation). The safety, feasibility and preferred type of thermal ablation(s) is at the discretion of the interventional radiologist (whether or not combined with surgical resection).
Primary Outcome Measure Information:
Title
Overall survival (OS) per patient
Description
Primary objective is to compare overall survival (OS) in both study arms, counting from the date of randomization to the date of death of the patient or to the last day of follow-up (censored).
Time Frame
5 years
Secondary Outcome Measure Information:
Title
Distant progression-free survival (DPFS) per patient
Description
Distant progression free survival (DPFS; per patient analysis): Overall DPFS is defined as the time from randomization to the time of disease progression (according to the RECIST 1.1 guideline) or cancer related death (events), death related to other causes is considered a competing risk
Time Frame
5 years
Title
Local tumor progression-free survival (LTPFS) per patient and per tumor treated
Description
Local tumor progression free survival (LTPFS; per tumor and per patient analysis): Overall LTPFS is defined as the time from randomization to the time of local disease progression, new metastases (events), censoring the date of death from any cause (competing risk), completion ablations performed within 6 weeks for residual tumor are not considered events for the local tumor progression analysis
Time Frame
5 years
Title
Systemic therapy related toxicity per patient following neoadjuvant systemic therapy
Description
Systemic therapy related toxicity is graded from 1 to 5 according to the CTCAE version 5.0
Time Frame
5 years
Title
Procedural morbidity and mortality per patient following repeat local treatment
Description
Procedural morbidity and mortality are graded from I to V according to the standard classification of surgical complications
Time Frame
5 years
Title
Length of hospital stay per patient following repeat local treatment
Description
In days
Time Frame
5 years
Title
Assessment of pain per patient
Description
- Pain assessment using visual analogue scale questionnaires (VAS; per procedure analysis: Assessed prior to, directly after and every three months after local treatment;
Time Frame
5 years
Title
Quality of life (QoL) per patient
Description
- To determine quality of life in both treatment arms. Quality of life assessment using EORCT QLQ-C30, EQ-5D, and PRODISQ questionnaires (per procedure analysis): Assessed prior to, and every three months after local treatment, assessed prior to, during and after neoadjuvant systemic therapy
Time Frame
5 years
Title
Quality-adjusted life years (QALY) per patient
Description
- Quality-adjusted life years (QALY) per treatment arm (per patient analysis).
Time Frame
5 years
Title
Cost-effectiveness ratio (ICER)
Description
- Direct and indirect total costs of care per treatment arm, and incremental cost-effectiveness ratio (ICER)
Time Frame
5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria Age >18 years Good performance status (ECOG 0-2 // ASA 1-3) Histological documentation of primary colorectal tumor Local treatment performed for initial CRLM New recurrence ≤12 months ≥1 locally treatable CRLM (resectable* and/or ablatable) Total number of new CRLM ≤5 Chemo-naïve or history of response to CAPOX/FOLFOX/FOLRIRI Life expectancy of at least 12 weeks Adequate bone marrow, liver and renal function Written informed consent Exclusion criteria Extrahepatic disease MSI/dMMR Radical local treatment unfeasible or unsafe (e.g. insufficient future liver volume) Compromised liver function (e.g. signs of portal hypertension, INR > 1,5 without use of anticoagulants, ascites) Uncontrolled infections (> grade 2 NCI-CTC version 3.0) Pregnant or breast-feeding subjects Immuno- or chemotherapy ≤ 6 weeks prior to the randomization Severe allergy to contrast media not controlled with premedication Substance abuse, medical, psychological or social conditions that may interfere with the subject's participation in the study or evaluation of the study results ECOG = Eastern Cooperative Oncology Group, ASA = American Society of Anesthesiologists, MSI = Microsatellite instability, dMMR = deficient mismatch repair * Resection for resectable lesions considered possible obtaining negative resection margins (R0) and preserving adequate liver reserve
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
M Dijkstra
Phone
+31(0)204444444
Email
interventieradiologie@vumc.nl
Facility Information:
Facility Name
Amsterdam UMC
City
Amsterdam
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
M Dijkstra
Phone
+31(0)204444444
Email
interventieradiologie@vumc.nl

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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COLLISION RELAPSE Trial

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