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

Not Applicable
Recruiting
Conditions
Multi-organ Metastatic Colorectal Cancer
Interventions
Drug: XELOX regimen according to standard procedures
Drug: FOLFOX regimen according to standard procedures
Procedure: Surgery
Procedure: tumor biopsy
Other: radiofrequency ablation (RFA)
Other: transarterial chemo-embolization using irinotecan drug-eluted beads ((DEBIRI-)TACE)
Radiation: stereotactic body radiation therapy (SBRT)
Drug: Bevacizumab
Registration Number
NCT01792934
Lead Sponsor
Radboud University Medical Center
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
478
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.

  • To meet the inclusion criteria a cytological analysis should be performed in case of any uncertainty about the presence of a lesion e.g. a false positive or false negative result on imaging.

  • 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.

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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.

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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
XELOX or FOLFOX regimenFOLFOX regimen according to standard proceduresXELOX or FOLFOX regimen
XELOX or FOLFOX regimenXELOX regimen according to standard proceduresXELOX or FOLFOX regimen
XELOX or FOLFOX regimentumor biopsyXELOX or FOLFOX regimen
XELOX or FOLFOX regimen and maximal tumor debulkingXELOX regimen according to standard proceduresXELOX 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).
XELOX or FOLFOX regimen and maximal tumor debulkingFOLFOX regimen according to standard proceduresXELOX 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).
XELOX or FOLFOX regimen and maximal tumor debulkingSurgeryXELOX 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).
XELOX or FOLFOX regimen and maximal tumor debulkingradiofrequency ablation (RFA)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).
XELOX or FOLFOX regimen and maximal tumor debulkingtransarterial chemo-embolization using irinotecan drug-eluted beads ((DEBIRI-)TACE)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).
XELOX or FOLFOX regimen and maximal tumor debulkingstereotactic body radiation therapy (SBRT)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).
XELOX or FOLFOX regimen and maximal tumor debulkingBevacizumabXELOX 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).
XELOX or FOLFOX regimen and maximal tumor debulkingtumor biopsyXELOX 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).
XELOX or FOLFOX regimenBevacizumabXELOX or FOLFOX regimen
Primary Outcome Measures
NameTimeMethod
Overall survivalfrom date of study inclusion until the date of death or until the end of follow up, assessed up to 10 years
Secondary Outcome Measures
NameTimeMethod
Progression free survival ratesdate of study inclusion to the first event defined as local recurrence or progression, distant recurrence or death from any cause assessed up to 10 years
Response ratesassessed every 3 months, after a follow up of 3 years assessed every 6 months
Safety and efficacy of the additional local treatment measured by number of serious adverse events.assessed after inclusion of 25, 50 and 100 patients, after 30% of the patients are included in the study for 12 months and after the end of follow up, assessed up to 10 years

Trial Locations

Locations (29)

Amstelveen Ziekenhuis

🇳🇱

Amstelveen, Netherlands

VU Medical Center

🇳🇱

Amsterdam, Netherlands

Sint Antonius Ziekenhuis

🇳🇱

Nieuwegein, Netherlands

IJsselland ziekenhuis

🇳🇱

Rotterdam, Netherlands

Zaans Medisch Centrum

🇳🇱

Zaandam, Netherlands

Isala Klinieken

🇳🇱

Zwolle, Netherlands

Meander Medisch Centrum

🇳🇱

Amersfoort, Netherlands

Antoni van Leeuwenhoek

🇳🇱

Amsterdam, Netherlands

Amphia Ziekenhuis

🇳🇱

Breda, Netherlands

Albert Schweizer ziekenhuis

🇳🇱

Dordrecht, Netherlands

Bravis ziekenhuis

🇳🇱

Roosendaal, Netherlands

Gelre

🇳🇱

Apeldoorn, Netherlands

Jeroen Bosch Ziekenhuis

🇳🇱

Den Bosch, Netherlands

Maxima Medisch Centrum

🇳🇱

Eindhoven, Netherlands

Medisch Centrum Leeuwarden

🇳🇱

Leeuwarden, Netherlands

Ziekenhuisgroep Twente

🇳🇱

Almelo, Netherlands

Noordwest Ziekenhuis Groep

🇳🇱

Alkmaar, Netherlands

Medisch Centrum Haaglanden

🇳🇱

Den Haag, Netherlands

Deventer Ziekenhuis

🇳🇱

Deventer, Netherlands

Dijklander

🇳🇱

Hoorn, Netherlands

Medisch Spectrum Twente

🇳🇱

Enschede, Netherlands

Radboud University Medical Center

🇳🇱

Nijmegen, Netherlands

Erasmus University Medical Center

🇳🇱

Rotterdam, Netherlands

Franciscus Gasthuis

🇳🇱

Rotterdam, Netherlands

Maasstadziekenhuis

🇳🇱

Rotterdam, Netherlands

Elisabeth Tweesteden Ziekenhuis

🇳🇱

Tilburg, Netherlands

Admiraal de Ruyter Hospital

🇳🇱

Vlissingen, Netherlands

University College London Hospital

🇬🇧

London, United Kingdom

University Hospital Southampton

🇬🇧

Southampton, United Kingdom

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