Multi-organ Metastatic Colorectal CancerORCHESTRANCT01792934
Chemotherapy and Maximal Tumor Debulking of Multi-organ Colorectal Cancer Metastases
A study testing XELOX regimen according to standard procedures, FOLFOX regimen according to standard procedures and Surgery in people with Multi-organ Metastatic Colorectal Cancer, run by Radboud University Medical Center at 29 sites in 2 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multi-organ Metastatic Colorectal Cancer
- What is being tested?
- XELOX regimen according to standard procedures, FOLFOX regimen according to standard procedures and Surgery
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 478 participants
- Where
- 29 sitesin 2 countries
- Study dates
- May 2013to May 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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;
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- 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.
Trial locations and contacts
29 sites in 2 countries.
29 sites in 2 countries
Netherlands27 sites
Jeroen Bosch Ziekenhuis
's-Hertogenbosch
Noordwest Ziekenhuis Groep
Alkmaar
Ziekenhuisgroep Twente
Almelo
Meander Medisch Centrum
Amersfoort
Amstelveen Ziekenhuis
Amstelveen
VU Medical Center
Amsterdam, NL-1081 HV
Antoni van Leeuwenhoek
Amsterdam
Gelre
Apeldoorn
Amphia Ziekenhuis
Breda
Deventer Ziekenhuis
Deventer
Albert Schweizer ziekenhuis
Dordrecht
Maxima Medisch Centrum
Eindhoven
Medisch Spectrum Twente
Enschede
Admiraal de Ruyter Hospital
Flushing
Dijklander
Hoorn
Medisch Centrum Leeuwarden
Leeuwarden
Sint Antonius Ziekenhuis
Nieuwegein
Radboud University Medical Center
Nijmegen
Bravis ziekenhuis
Roosendaal
Erasmus University Medical Center
Rotterdam, NL-3075 EA
Franciscus Gasthuis
Rotterdam
IJsselland ziekenhuis
Rotterdam
Maasstadziekenhuis
Rotterdam
Medisch Centrum Haaglanden
The Hague
Elisabeth Tweesteden Ziekenhuis
Tilburg
Zaans Medisch Centrum
Zaandam
Isala Klinieken
Zwolle
United Kingdom2 sites
University College London Hospital
London
University Hospital Southampton
Southampton
About this study
Official title: 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.
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
- Being tested
- XELOX regimen according to standard procedures, FOLFOX regimen according to standard procedures, Surgery, radiofrequency ablation (RFA), transarterial chemo-embolization using irinotecan drug-eluted beads ((DEBIRI-)TACE)
- Keywords
- Debulking, cytoreduction, RFA, SABR, palliative chemotherapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
XELOX regimen according to standard proceduresDrug
FOLFOX regimen according to standard proceduresDrug
SurgeryProcedure or surgery
radiofrequency ablation (RFA)Other
transarterial chemo-embolization using irinotecan drug-eluted beads ((DEBIRI-)TACE)Other
stereotactic body radiation therapy (SBRT)Radiation
BevacizumabDrug
may be added to both regimens according to standard procedures
tumor biopsyProcedure or surgery
at baseline (diagnostic or study) biopsy and after 3 or 4 cycles an optional tumor biopsy
| Study group | Role | What they receive |
|---|---|---|
| XELOX or FOLFOX regimen | Active comparator | XELOX or FOLFOX regimen Receives: Drug: XELOX regimen according to standard procedures; Drug: FOLFOX regimen according to standard procedures; Drug: Bevacizumab; Procedure: tumor biopsy |
| XELOX or FOLFOX regimen and maximal tumor debulking | Experimental | 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). Receives: Drug: XELOX regimen according to standard procedures; Drug: FOLFOX regimen according to standard procedures; Procedure: Surgery; Other: radiofrequency ablation (RFA); Other: transarterial chemo-embolization using irinotecan drug-eluted beads ((DEBIRI-)TACE); Radiation: stereotactic body radiation therapy (SBRT); Drug: Bevacizumab; Procedure: tumor biopsy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall survival
Measured: 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
Measured: 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
Measured: 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.
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Feb 2013 (estimated)
- Study startMay 2013
- Primary completionMay 2028 (estimated)
- Study completionMay 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Multi-organ Metastatic Colorectal CancerStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 478 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Erasmus Medical Center
- Responsible party
- Sponsor
- Investigators
- H.M.W. Verheul, MD PhD, Principal investigator, Radboud University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01792934
- Sponsor's protocol ID
- 2012-073
- Acronym
- ORCHESTRA
- Status last verified
- Mar 2025
- First submitted
- 20 Dec 2012
- Last updated
- 20 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Gootjes EC, Bakkerus L, Adhin AA, Zonderhuis BM, Versteeg KS, Tuynman JB, Meijerink MR, Haasbeek CJA, de Wilt JHW, Grunhagen DJ, Smit EJ, Primrose JM, Bridgewater J, van Meerten E, de Groot JB, Hendriks MP, Oomen-de Hoop E, Buffart TE, Verhoef C, Verheul HMW; ORCHESTRA Study Group. Tumor Debulking in Combination With Chemotherapy in Multiorgan Metastatic Colorectal Cancer: The ORCHESTRA Randomized Clinical Trial. JAMA. 2026 Apr 21;335(15):1311-1320. doi: 10.1001/jama.2026.1929.
PubMed 41837962Bakkerus 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.
PubMed 37856212
Study at a glance
From the registry record, last updated by the sponsor on 20 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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.
- ClinicalTrials.gov ID
- NCT01792934
- Acronym / sponsor ID
- ORCHESTRA / 2012-073
- Conditions
- Multi-organ Metastatic Colorectal Cancer
- Keywords
- Debulking, cytoreduction, RFA, SABR, palliative chemotherapy
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 478 participants (estimated)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Collaborators
- Erasmus Medical Center
- Study start
- May 2013 (actual)
- Primary completion
- May 2028 (estimated)
- Study completion
- May 2028 (estimated)
- First posted
- 15 Feb 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| XELOX or FOLFOX regimen | Active comparator | Drug: XELOX regimen according to standard procedures, Drug: FOLFOX regimen according to standard procedures, Drug: Bevacizumab, Procedure: tumor biopsyXELOX or FOLFOX regimen |
| XELOX or FOLFOX regimen and maximal tumor debulking | Experimental | Drug: XELOX regimen according to standard procedures, Drug: FOLFOX regimen according to standard procedures, Procedure: Surgery, Other: radiofrequency ablation (RFA), Other: transarterial chemo-embolization using irinotecan drug-eluted beads ((DEBIRI-)TACE), Radiation: stereotactic body radiation therapy (SBRT), Drug: Bevacizumab, Procedure: tumor 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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- 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)
- 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.
Key exclusion criteria (16 listed)
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| XELOX regimen according to standard procedures | Drug | XELOX or FOLFOX regimen, XELOX or FOLFOX regimen and maximal tumor debulking |
| FOLFOX regimen according to standard procedures | Drug | XELOX or FOLFOX regimen, XELOX or FOLFOX regimen and maximal tumor debulking |
| Surgery | Procedure or surgery | XELOX or FOLFOX regimen and maximal tumor debulking |
| radiofrequency ablation (RFA) | Other | XELOX or FOLFOX regimen and maximal tumor debulking |
| transarterial chemo-embolization using irinotecan drug-eluted beads ((DEBIRI-)TACE) | Other | XELOX or FOLFOX regimen and maximal tumor debulking |
| stereotactic body radiation therapy (SBRT) | Radiation | XELOX or FOLFOX regimen and maximal tumor debulking |
| Bevacizumabmay be added to both regimens according to standard procedures | Drug | XELOX or FOLFOX regimen, XELOX or FOLFOX regimen and maximal tumor debulking |
| tumor biopsyat baseline (diagnostic or study) biopsy and after 3 or 4 cycles an optional tumor biopsy | Procedure or surgery | XELOX or FOLFOX regimen, XELOX or FOLFOX regimen and maximal tumor debulking |
Primary outcome
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
3 secondary outcomes
Progression free survival rates
Time frame: 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
Time frame: 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.
Time frame: 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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Aug 2026.
- Derived from this study: PubMed 41837962Gootjes EC, Bakkerus L, Adhin AA, Zonderhuis BM, Versteeg KS, Tuynman JB, Meijerink MR, Haasbeek CJA, de Wilt JHW, Grunhagen DJ, Smit EJ, Primrose JM, Bridgewater J, van Meerten E, de Groot JB, Hendriks MP, Oomen-de Hoop E, Buffart TE, Verhoef C, Verheul HMW; ORCHESTRA Study Group. Tumor Debulking in Combination With Chemotherapy in Multiorgan Metastatic Colorectal Cancer: The ORCHESTRA Randomized Clinical Trial. JAMA. 2026 Apr 21;335(15):1311-1320. doi: 10.1001/jama.2026.1929.
- Derived from this study: PubMed 37856212Bakkerus 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
H.M.W. Verheul, MD PhD principal investigator
Radboud University Medical Center
29 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing XELOX regimen according to standard procedures, FOLFOX regimen according to standard procedures and Surgery in people with Multi-organ Metastatic Colorectal Cancer, run by Radboud University Medical Center at 29 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 20 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 29 sites in Netherlands, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01792934, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Aug 2026; AzTrials last refreshed its copy on 8 Nov 2026.