Chemotherapy and Maximal Tumor Debulking of Multi-organ Colorectal Cancer Metastases

NCT ID: NCT01792934

Last Updated: 2025-04-15

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 478 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-05-31
• Study Completion Date: 2027-07-31

Brief Summary

The purpose of this study is to compare overall survival rates of colorectal cancer patients with multi-organ metastases with an indication for first line systemic treatment randomized for treatment with combination chemotherapy or treatment with combination chemotherapy and additional maximal tumor debulking including surgical tumor resection, RFA, (DEBIRI-)TACE and SBRT, depending on best clinical judgement according to a standardized treatment algorithm. Our hypothesis is that maximal tumor debulking in addition to systemic treatment with chemotherapy and biologicals will provide an improvement in progression free and overall survival in this patient group.

Conditions

Multi-organ Metastatic Colorectal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

XELOX or FOLFOX regimen

XELOX or FOLFOX regimen

Group Type: ACTIVE_COMPARATOR

XELOX regimen according to standard procedures

Intervention Type: DRUG

FOLFOX regimen according to standard procedures

Intervention Type: DRUG

Bevacizumab

Intervention Type: DRUG

may be added to both regimens according to standard procedures

tumor biopsy

Intervention Type: PROCEDURE

at baseline (diagnostic or study) biopsy and after 3 or 4 cycles an optional tumor biopsy

XELOX or FOLFOX regimen and maximal tumor debulking

XELOX or FOLFOX regimen and maximal tumor debulking including Surgery, radiofrequency ablation (RFA), transarterial chemo-embolization using irinotecan drug-eluted beads ((DEBIRI)-TACE) or stereotactic body radiation therapy (SBRT).

Group Type: EXPERIMENTAL

XELOX regimen according to standard procedures

Intervention Type: DRUG

FOLFOX regimen according to standard procedures

Intervention Type: DRUG

Surgery

Intervention Type: PROCEDURE

radiofrequency ablation (RFA)

Intervention Type: OTHER

transarterial chemo-embolization using irinotecan drug-eluted beads ((DEBIRI-)TACE)

Intervention Type: OTHER

stereotactic body radiation therapy (SBRT)

Intervention Type: RADIATION

Bevacizumab

Intervention Type: DRUG

may be added to both regimens according to standard procedures

tumor biopsy

Intervention Type: PROCEDURE

at baseline (diagnostic or study) biopsy and after 3 or 4 cycles an optional tumor biopsy

Interventions

XELOX regimen according to standard procedures

Intervention Type: DRUG

FOLFOX regimen according to standard procedures

Intervention Type: DRUG

Surgery

Intervention Type: PROCEDURE

radiofrequency ablation (RFA)

Intervention Type: OTHER

transarterial chemo-embolization using irinotecan drug-eluted beads ((DEBIRI-)TACE)

Intervention Type: OTHER

stereotactic body radiation therapy (SBRT)

Intervention Type: RADIATION

Bevacizumab

may be added to both regimens according to standard procedures

Intervention Type: DRUG

tumor biopsy

at baseline (diagnostic or study) biopsy and after 3 or 4 cycles an optional tumor biopsy

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Histological or cytological documentation of cancer is required.
• Indication for first line palliative systemic treatment for metastatic colorectal cancer (mCRC).
• Patients with CRC metastases in (the primary tumor is excluded as metastatic site)

• ≥ 2 different organs if at least >1 extra-hepatic metastases or
• ≥ 2 different organs including >5 hepatic metastases not located to one lobe or
• ≥ 2 different organs including either a positive para-aortal lymph nodes or celiac lymph nodes or adrenal metastases or pleural carcinomatosis or peritoneal carcinomatosis
• Feasible radical tumor debulking. Incomplete tumor debulking is allowed only if at least 80% of metastases can be treated.
• Age ≥ 18 years.
• WHO performance status 0 - 1.
• Life expectancy of at least 12 weeks.
• Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to screening:

• Hemoglobin ≥ 5.6 mmol/L;
• Absolute neutrophil count (ANC) ≥ 1,500/mm3;
• Platelet count ≥ 100*109/l;
• Total bilirubin ≤ 1.5 times the upper limit of normal;
• ALT and AST ≤ 2.5 x upper limit of normal (≤ 5 x upper limit of normal for subjects with liver involvement of their cancer);
• Albumin > 30 g/l;
• Serum creatinine ≤ 1.5 x upper limit of normal or a MDRD ≥ 50 ml/min;
• 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.
• 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).
• Written informed consent.

Exclusion Criteria

• Prior (neo-)adjuvant chemotherapy for < 6 months after last treatment and first detection of extra-hepatic metastases, except for neoadjuvant capecitabine in the context of chemoradiation for rectal carcinoma.
• Candidates for HIPEC.
• Patients with liver metastases only
• Evidence of brain metastases.
• History of other prior malignancy except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer. Patients with other malignancies are eligible if they have remained disease free for at least 5 years.- History of cardiac disease:

• Congestive heart failure >NYHA class 2;
• Active Coronary Artery Disease (defined as myocardial infarction within 6 months prior to screening);
• Cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted).
• Uncontrolled hypertension. Blood pressure must be ≤160/95 mm Hg 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.
• Uncontrolled infections (> grade 2 NCI-CTC version 4.0).
• Pregnant or breast-feeding 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.
• Concurrent anticancer chemotherapy, immunotherapy or investigational drug therapy during the study or within 4 weeks of the start of study drug.
• Concomitant use of dexamethasone, anticonvulsants and anti-arrhythmic drugs other than digoxin or beta blockers.
• Severe allergy for 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.
• Any condition that is unstable or could jeopardize the safety of the subject and their compliance in the study.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Erasmus Medical Center

OTHER

Sponsor Role: collaborator

Radboud University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

H.M.W. Verheul, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Radboud University Medical Center

Locations

Jeroen Bosch Ziekenhuis

's-Hertogenbosch, , Netherlands

Noordwest Ziekenhuis Groep

Alkmaar, , Netherlands

Ziekenhuisgroep Twente

Almelo, , Netherlands

Meander Medisch Centrum

Amersfoort, , Netherlands

Amstelveen Ziekenhuis

Amstelveen, , Netherlands

VU Medical Center

Amsterdam, , Netherlands

Antoni van Leeuwenhoek

Amsterdam, , Netherlands

Gelre

Apeldoorn, , Netherlands

Amphia Ziekenhuis

Breda, , Netherlands

Deventer Ziekenhuis

Deventer, , Netherlands

Albert Schweizer ziekenhuis

Dordrecht, , Netherlands

Maxima Medisch Centrum

Eindhoven, , Netherlands

Medisch Spectrum Twente

Enschede, , Netherlands

Admiraal de Ruyter Hospital

Flushing, , Netherlands

Dijklander

Hoorn, , Netherlands

Medisch Centrum Leeuwarden

Leeuwarden, , Netherlands

Sint Antonius Ziekenhuis

Nieuwegein, , Netherlands

Radboud University Medical Center

Nijmegen, , Netherlands

Bravis ziekenhuis

Roosendaal, , Netherlands

Erasmus University Medical Center

Rotterdam, , Netherlands

Franciscus Gasthuis

Rotterdam, , Netherlands

IJsselland ziekenhuis

Rotterdam, , Netherlands

Maasstadziekenhuis

Rotterdam, , Netherlands

Medisch Centrum Haaglanden

The Hague, , Netherlands

Elisabeth Tweesteden Ziekenhuis

Tilburg, , Netherlands

Zaans Medisch Centrum

Zaandam, , Netherlands

Isala Klinieken

Zwolle, , Netherlands

University College London Hospital

London, , United Kingdom

University Hospital Southampton

Southampton, , United Kingdom

Countries

Netherlands; United Kingdom

References

Bakkerus L, Buffart LM, Buffart TE, Meyer YM, Zonderhuis BM, Haasbeek CJA, Versteeg KS, Loosveld OJL, de Groot JWB, Hendriks MP, Verhoef C, Verheul HMW, Gootjes EC. Health-Related Quality of Life in Patients With Metastatic Colorectal Cancer Undergoing Systemic Therapy With or Without Maximal Tumor Debulking. J Natl Compr Canc Netw. 2023 Oct;21(10):1059-1066.e5. doi: 10.6004/jnccn.2023.7050.

Reference Type: DERIVED

PMID: 37856212 (View on PubMed)

Other Identifiers

2012-073

Identifier Type: -

Identifier Source: org_study_id