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

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ClinicalTrials.gov Identifier: NCT01792934
Recruitment Status : Recruiting
First Posted : February 15, 2013
Last Update Posted : August 1, 2017
Sponsor:
Collaborator:
Erasmus Medical Center
Information provided by (Responsible Party):
H.M.W. Verheul, VU 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.

Condition or disease Intervention/treatment Phase
Multi-organ Metastatic Colorectal Cancer 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 Not Applicable

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 478 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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.
Actual Study Start Date : May 2013
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: XELOX or FOLFOX regimen
XELOX or FOLFOX regimen
Drug: XELOX regimen according to standard procedures
Drug: FOLFOX regimen according to standard procedures
Drug: Bevacizumab
may be added to both regimens according to standard procedures

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

Experimental: 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).
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
may be added to both regimens according to standard procedures

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




Primary Outcome Measures :
  1. 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 Outcome Measures :
  1. 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 ]
  2. Response rates [ Time Frame: assessed every 3 months, after a follow up of 3 years assessed every 6 months ]
  3. 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 ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 - 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01792934


Contacts
Contact: H.M.W. Verheul, MD PhD 0031 (0)20 4444321 h.verheul@vumc.nl

Locations
Netherlands
Noordwest Ziekenhuis Groep Recruiting
Alkmaar, Netherlands
Contact: MP Hendriks, Dr         
Principal Investigator: MP Hendriks, Dr         
Ziekenhuisgroep Twente Recruiting
Almelo, Netherlands
Contact: R Hoekstra, R         
Principal Investigator: R Hoekstra, R         
Meander Medisch Centrum Recruiting
Amersfoort, Netherlands
Contact: HJ Bloemendal, HJ         
Principal Investigator: HJ Bloemendal, Dr         
Amstelveen Ziekenhuis Recruiting
Amstelveen, Netherlands
Contact: AA van Zweeden, Drs         
Principal Investigator: AA van Zweeden, Drs         
VU Medical Center Recruiting
Amsterdam, Netherlands, NL-1081 HV
Contact: H.M.W. Verheul, MD, PhD    0031-20-4444321    h.verheul@vumc.nl   
Principal Investigator: H.M.W. Verheul, MD, PhD         
Academisch Medisch Centrum Recruiting
Amsterdam, Netherlands
Contact: PJ Tanis, Dr         
Principal Investigator: PJ Tanis, Dr         
Onze Lieve Vrouwe Gasthuis Not yet recruiting
Amsterdam, Netherlands
Contact: JM Meerum Terwogt, Dr         
Principal Investigator: JM Meerum Terwogt, Dr         
Amphia Ziekenhuis Recruiting
Breda, Netherlands
Contact: A Ten Tije, Dr         
Principal Investigator: A Ten Tije, Dr         
Medisch Centrum Haaglanden Recruiting
Den Haag, Netherlands
Contact: HH Helgason, Dr         
Principal Investigator: HH Helgason, Dr         
Deventer Ziekenhuis Recruiting
Deventer, Netherlands
Contact: H Torrenga, Dr         
Principal Investigator: H Torrenga, Dr         
Albert Schweizer ziekenhuis Recruiting
Dordrecht, Netherlands
Contact: M Trajkovic, MD         
Principal Investigator: M Trajkovic, MD         
Maxima Medisch Centrum Recruiting
Eindhoven, Netherlands
Contact: G Vreugdenhil, Dr         
Principal Investigator: G Vreugdenhil, Dr         
Universitair Medisch Centrum Groningen Recruiting
Groningen, Netherlands
Contact: GAP Hospers, Prof Dr         
Principal Investigator: GAP Hospers, Dr         
Spaarne ziekenhuis Recruiting
Hoofddorp, Netherlands
Contact: A Beeker, Drs.         
Principal Investigator: A Beeker, Drs         
Medisch Centrum Leeuwarden Recruiting
Leeuwarden, Netherlands
Contact: M Polee, Dr         
Principal Investigator: M Polee, Dr         
Academisch ziekenhuis Maastricht Recruiting
Maastricht, Netherlands
Contact: RLH Jansen, Dr         
Principal Investigator: RLH Jansen, Dr         
Sint Antonius Ziekenhuis Recruiting
Nieuwegein, Netherlands
Contact: M Los, Dr         
Principal Investigator: M Los, Dr         
UMC Sint Radboud Recruiting
Nijmegen, Netherlands
Contact: SA Radema, Dr         
Principal Investigator: SA Radema, Dr         
Bravis ziekenhuis Recruiting
Roosendaal, Netherlands
Contact: Troost         
Principal Investigator: Troost         
Erasmus University Medical Center Recruiting
Rotterdam, Netherlands, NL-3075 EA
Contact: C. Verhoef, MD PhD    0031 (0)10 7040704    c.verhoef@erasmusmc.nl   
Principal Investigator: C. Verhoef, MD PhD         
Franciscus Gasthuis Recruiting
Rotterdam, Netherlands
Contact: P Hamberg, Dr         
Principal Investigator: P Hamberg, Dr         
IJsselland ziekenhuis Recruiting
Rotterdam, Netherlands
Contact: Vermaas         
Principal Investigator: Vermaas         
Maasstadziekenhuis Recruiting
Rotterdam, Netherlands
Contact: TC Kok, Dr         
Principal Investigator: TC Kok, Dr         
Elisabeth Tweesteden Ziekenhuis Recruiting
Tilburg, Netherlands
Contact: L Beerepoot, Dr         
Principal Investigator: L Beerepoot, Dr         
Diakonessenhuis Utrecht Recruiting
Utrecht, Netherlands
Contact: D Ten Bokkel Huinink, Dr         
Principal Investigator: D Ten Bokkel Huinink, Dr         
Universitait Medisch Centrum Utrecht Not yet recruiting
Utrecht, Netherlands
Contact: IHM Borel Rinkes, Prof Dr         
Principal Investigator: IHM Rinkes, IHM         
Admiraal de Ruyter Hospital Recruiting
Vlissingen, Netherlands
Contact: van Halteren         
Principal Investigator: van Halteren         
Jeroen Bosch Ziekenhuis Not yet recruiting
Zaltbommel, Netherlands
Contact: JFM Pruijt, Dr         
Principal Investigator: JFM Pruijt, Dr         
Isala Klinieken Recruiting
Zwolle, Netherlands
Contact: JWB de Groot, Dr         
Principal Investigator: JWB de Groot, Dr         
Sponsors and Collaborators
VU University Medical Center
Erasmus Medical Center
Investigators
Principal Investigator: H.M.W. Verheul, MD PhD VU University Medical Center

Responsible Party: H.M.W. Verheul, Head Department Medical Oncology, VU University Medical Center
ClinicalTrials.gov Identifier: NCT01792934     History of Changes
Other Study ID Numbers: 2012-073
First Posted: February 15, 2013    Key Record Dates
Last Update Posted: August 1, 2017
Last Verified: July 2017

Keywords provided by H.M.W. Verheul, VU University Medical Center:
Debulking, cytoreduction, RFA, SABR, palliative chemotherapy

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Bevacizumab
Irinotecan
Oxaliplatin
Fluorouracil
Leucovorin
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimetabolites
Antimetabolites, Antineoplastic
Immunosuppressive Agents