Chemotherapy and Maximal Tumor Debulking of Multi-organ Colorectal Cancer Metastases
ORCHESTRA
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.
1 other identifier
interventional
478
2 countries
29
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for not_applicable
Started May 2013
Longer than P75 for not_applicable
29 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 20, 2012
CompletedFirst Posted
Study publicly available on registry
February 15, 2013
CompletedStudy Start
First participant enrolled
May 1, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
July 1, 2027
ExpectedApril 15, 2025
March 1, 2025
11.7 years
December 20, 2012
April 10, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Overall survival
from date of study inclusion until the date of death or until the end of follow up, assessed up to 10 years
Secondary Outcomes (3)
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
Study Arms (2)
XELOX or FOLFOX regimen
ACTIVE COMPARATORXELOX or FOLFOX regimen
XELOX or FOLFOX regimen and maximal tumor debulking
EXPERIMENTALXELOX 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).
Interventions
may be added to both regimens according to standard procedures
at baseline (diagnostic or study) biopsy and after 3 or 4 cycles an optional tumor biopsy
Eligibility Criteria
You may qualify if:
- 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;
- +6 more criteria
You may not qualify if:
- 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.
- +1 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Radboud University Medical Centerlead
- Erasmus Medical Centercollaborator
Study Sites (29)
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, NL-1081 HV, 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, NL-3075 EA, 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
Related Publications (1)
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.
PMID: 37856212DERIVED
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
H.M.W. Verheul, MD PhD
Radboud University Medical Center
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 20, 2012
First Posted
February 15, 2013
Study Start
May 1, 2013
Primary Completion
January 1, 2025
Study Completion (Estimated)
July 1, 2027
Last Updated
April 15, 2025
Record last verified: 2025-03