A randomised multicenter clinical trial for patients with multi-organ, colorectal cancer metastases comparing the combination of chemotherapy and removing as many visible tumors as possible by surgery or other means versus chemotherapy alone

Not Applicable

• Conditions: Multi-organ, colorectal cancer metastases; Cancer

• Registration Number: ISRCTN15067672
• Lead Sponsor: Radboud University Medical Centre Nijmegen (Netherlands)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-02-07
• Last Update Posted: 30 January 2023
• Study Completion: 2025-07-01

Recruitment & Eligibility

• Status: Ongoing
• Sex: All
• Target Recruitment: 478

Inclusion Criteria

1. Patients with CRC metastases in = 2 different organs and
1.1. >3 extrahepatic metastases or
1.2. >5 hepatic metastases not located to one lobe or
1.3. =1 hepatic metastases and either positive para-aortal lymph nodes or celiac lymph nodes or adrenal metastases or pleural carcinomatosis or peritoneal carcinomatosis
1.4. The primary tumor is excluded as metastatic site
2. Feasible radical tumor debulking. Incomplete tumor debulking is allowed only if at least 80% of metastases can be treated
3. Age >= 18 years
4. WHO performance status 0 – 1
5. Life expectancy of at least 12 weeks
6. Written informed consent

Exclusion Criteria

1. Prior (neo-)adjuvant chemotherapy for < 6 months after last treatment and first detection of extrahepatic metastases, except for neoadjuvant capecitabin in the context of chemoradiation for rectal carcinoma
2. Candidates for HIPEC
3. Patients with liver metastases only
4. Evidence of brain metastases
5. History of other prior malignancy except for adequately treated basal cell or squamous cell skin cancer or in-situ carcinoma of any organ. Patients with other malignancies are eligible if they have remained disease free for at least 5 years
6. History of cardiac disease:
6.1. Congestive heart failure >NYHA class 2
6.2. Active Coronary Artery Disease (defined as myocardial infarction within 6 months prior to screening)
6.3. Cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted)
7. Uncontrolled hypertension. Blood pressure must be =160/95 mmHg at the time of screening on a stable antihypertensive regimen. Blood pressure must be stable on at least 3 separate measurements on at least 2 separate days
8. Uncontrolled infections (> grade 2 NCI-CTC version 4.0)
9. Pregnant or breastfeeding women. Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of treatment. Both men and women enrolled in this trial must agree to use adequate barrier birth control measures (e.g., cervical cap, condom, and diaphragm) or intrauterine device during the course of the trial. Oral birth control methods alone will not be considered adequate on this study, because of the potential pharmacokinetic interaction between study drug and oral contraceptives. Concomitant use of oral and barrier contraceptives is advised.
10. Concurrent anticancer chemotherapy, immunotherapy or investigational drug therapy during the study or within 4 weeks of the start of study drug
11. Concomitant chronic use of dexamethasone, anti-convulsants and anti-arrhythmic drugs other than digoxin or beta blockers
12. Severe allergy for contrast media not controlled with premedication
13. Substance abuse, medical, psychological or social conditions that may interfere with the subject’s participation in the study or evaluation of the study results
14. Any condition that is unstable or could jeopardize the safety of the subject and their compliance in the study

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Overall survival (OS), counting from the date of study inclusion to the date of death of the patient

Secondary Outcome Measures

Name	Time	Method
<br> 1. Progression-free survival measured using the inclusion date and the progression date. Progression measured using RECIST 1.1 scoring system for each CT scan at baseline, randomization (after 3 or 4 cycles of chemotherapy) and every 3 months until progressive disease<br> 2. Safety and efficacy of additional local treatment measured using scoring of Serious Adverse Events using the CTCAE version 4 and Clavien Dindo scoring systems when a SAE occurred<br> 3. Quality of life measured using the validated EORTC QLQ CR29 and C30 questionaires at baseline, randomization (after 3 or 4 cycles of chemotherapy) and every 3 months until progressive disease<br>