COLLISION RELAPSE trial Recurrent colorectal liver metastases: repeat local treatment +/- neoadjuvant systemic therapy, a phase III prospective randomized controlled trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Stichting Amsterdam UMC

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04], Diseases [C] - Digestive System Diseases [C06]

Trial duration

11 Dec 2024 → ongoing

Decision date (initial)

2024-12-11

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-515341-41-01

EudraCT number

2022-002214-17

ClinicalTrials.gov

NCT05861505

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

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 objectives 7

1. 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 (205)) or cancer related death (events), death related to other causes is considered a competing risk
2. 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
3. Rate of adverse events and serious adverse events (AE and SAE; per procedure analysis), associated with both treatment arms; o Systemic therapy related toxicity is graded from 1 to 5 according to the CTCAE version 5.0, discussed in paragraph 9.4; o Procedural morbidity and mortality are graded from I to V according to the standard classification of surgical complications (206), discussed in paragraph 9.4
4. Length of hospital stay
5. Pain assessment using visual analogue scale questionnaires (VAS; per procedure analysis: Assessed prior to, directly after and every three months after local treatment
6. 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 Version 3 May 12th 2023 31 of 140 every three months after local treatment, assessed prior to, during and after neoadjuvant systemic therapy
7. Direct and indirect total costs of care per treatment arm, quality-adjusted life years (QALY) and incremental cost-effectiveness ratio (ICER) per treatment arm (per patient analysis)

Conditions and MedDRA coding

Colorectal liver metastases

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Histological documentation of primary colorectal tumor
2. Local treatment performed for initial CRLM
3. At least one recurrent CRLM eligible for local treatment (partial hepatectomy and/or thermal ablation
4. Maximum number of CRLM 5
5. Resection for resectable lesions considered possible obtaining negative resection margins (R0) and preserving adequate liver reserve
6. Resectability and ablatability should be re-confirmed with full exploration for hepatic, peritoneal and regional lymph node metastases
7. Age >18 years
8. Eastern Cooperative Oncology Group performance status (ECOG) 0-2
9. American Society of Anesthesiologists (ASA) grade 1-3
10. Life expectancy of at least 12 weeks
11. Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to screening: Version 3 May 12th 2023 45 of 140 o Hemoglobin ≥ 5.6 mmol/L; o Absolute neutrophil count (ANC) ≥ 1,500/mm3; o Platelet count ≥ 100*109/l; o Total bilirubin ≤ 1.5 times the upper limit of normal; o ALT and AST ≤ 2.5 x upper limit of normal (≤ 5 x upper limit of normal for subjects with liver involvement of their cancer); o Albumine > 30 g/l; o Serum creatinine ≤ 1.5 x upper limit of normal or a MDRD ≥ 50 ml/min; o Prothrombin time or INR < 1.5 x ULN, unless coumarin derivates are used. Due to interactions with capecitabine, all patients using coumarin derivates will be treated with LMWH instead. o Activated partial thromboplastin time < 1.25 x ULN (therapeutic anticoagulation therapy is allowed if this treatment can be interrupted as judged by the treating physician).
12. Written informed consent

Exclusion criteria 12

1. No target lesions suitable for both resection and ablation
2. Radical treatment unfeasible or unsafe (e.g. insufficient FLR)
3. The presence of extrahepatic nodal or non-nodal metastases; see below for additional information regarding pulmonary nodules
4. Compromised liver function (e.g. signs of portal hypertension, INR > 1,5 without use of anticoagulants, ascites)
5. Uncontrolled infections (> grade 2 NCI-CTC version 3.0)
6. Pregnant or breast-feeding subjects. Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of treatment
7. Immunotherapy ≤ 6 weeks prior to the randomization
8. Chemotherapy ≤ 6 weeks prior to the randomization
9. Progression on both oxaliplatin and irinotecan
10. Severe allergy to contrast media not controlled with premedication
11. Substance abuse, medical, psychological or social conditions that may interfere with the subject’s participation in the study or evaluation of the study results
12. Microsatellite instability (MSI)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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 endpoints 7

1. 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 (205)) or cancer related death (events), death related to other causes is considered a competing risk
2. 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
3. Rate of adverse events and serious adverse events (AE and SAE; per procedure analysis), associated with both treatment arms; o Systemic therapy related toxicity is graded from 1 to 5 according to the CTCAE version 5.0, discussed in paragraph 9.4; o Procedural morbidity and mortality are graded from I to V according to the standard classification of surgical complications (206), discussed in paragraph 9.4
4. Length of hospital stay
5. Pain assessment using visual analogue scale questionnaires (VAS; per procedure analysis: Assessed prior to, directly after and every three months after local treatment
6. 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 Version 3 May 12th 2023 31 of 140 every three months after local treatment, assessed prior to, during and after neoadjuvant systemic therapy
7. Direct and indirect total costs of care per treatment arm, quality-adjusted life years (QALY) and incremental cost-effectiveness ratio (ICER) per treatment arm (per patient analysis)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Stichting Amsterdam UMC

Sponsor organisation

Stichting Amsterdam UMC

Address

De Boelelaan 1117

City

Amsterdam

Postcode

1081 HV

Country

Netherlands

Scientific contact point

Organisation

Stichting Amsterdam UMC

Contact name

Martijn Meijerink

Public contact point

Organisation

Stichting Amsterdam UMC

Contact name

Martijn Meijerink

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 3 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications