A Randomized Multicenter Clinical Trial for Patient With Multi-organ, Colorectal Cancer Metastases Comparing the Combination of Chemotherapy and Maximal Tumor Debulking Versus Chemotherapy Alone.
Overview
- Phase
- Not Applicable
- Intervention
- XELOX regimen according to standard procedures
- Conditions
- Multi-organ Metastatic Colorectal Cancer
- Sponsor
- Radboud University Medical Center
- Enrollment
- 478
- Locations
- 29
- Primary Endpoint
- Overall survival
- Status
- Active, not recruiting
- Last Updated
- last year
Overview
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.
Investigators
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.
- •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 -
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).
Arms & Interventions
XELOX or FOLFOX regimen
XELOX or FOLFOX regimen
Intervention: XELOX regimen according to standard procedures
XELOX or FOLFOX regimen
XELOX or FOLFOX regimen
Intervention: FOLFOX regimen according to standard procedures
XELOX or FOLFOX regimen
XELOX or FOLFOX regimen
Intervention: Bevacizumab
XELOX or FOLFOX regimen
XELOX or FOLFOX regimen
Intervention: 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).
Intervention: XELOX regimen according to standard procedures
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).
Intervention: FOLFOX regimen according to standard procedures
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).
Intervention: Surgery
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).
Intervention: radiofrequency ablation (RFA)
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).
Intervention: transarterial chemo-embolization using irinotecan drug-eluted beads ((DEBIRI-)TACE)
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).
Intervention: stereotactic body radiation therapy (SBRT)
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).
Intervention: Bevacizumab
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).
Intervention: tumor biopsy
Outcomes
Primary Outcomes
Overall survival
Time Frame: from date of study inclusion until the date of death or until the end of follow up, assessed up to 10 years
Secondary Outcomes
- Progression free survival rates(date 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 rates(assessed 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)