Maintenance Treatment Versus Observation After Induction in Advanced Colorectal Carcinoma
NCT ID: NCT00442637
Last Updated: 2013-12-12
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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UNKNOWN
PHASE3
635 participants
INTERVENTIONAL
2007-01-31
2013-12-31
Brief Summary
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In this study the effects of bevacizumab and low-dose continuous chemotherapy with capecitabine is investigated in patients who have responded to 6 courses of oxaliplatin, capecitabine and bevacizumab ("induction treatment", at standard doses). This treatment is continued until progression or severe toxicity. This regimen is compared to the effects a observation without treatment after the induction treatment.
In case of disease progression, induction treatment will be reintroduced.
Detailed Description
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Evidence, mainly preclinical, suggests that continuous dosing metronomic chemotherapy may be more efficacious than interval-chemotherapy given at MTD. In this study the concept of metronomic chemotherapy is explored by administering a continuous daily instead of the usual 2 weeks-on/1 week-off oral dosing regimen of low-dose capecitabine plus bevacizumab as maintenance therapy after induction combination chemotherapy given at MTD plus bevacizumab.
Conditions
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Keywords
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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1
observation
observation
observation after induction treatment
2
capecitabine plus bevacizumab
capecitabine + bevacizumab
Ca 1250 mg/m2 daily orally continuously, B 7.5 mg/kg i.v. q 3 w
Interventions
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capecitabine + bevacizumab
Ca 1250 mg/m2 daily orally continuously, B 7.5 mg/kg i.v. q 3 w
observation
observation after induction treatment
Eligibility Criteria
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Inclusion Criteria
* Distant metastases (patients with only local recurrence are not eligible);
* Unidimensionally measurable disease (\> 1 cm on spiral CT scan or \> 2 cm on chest X-ray; liver ultrasound is not allowed). Serum CEA may not be used as a parameter for disease evaluation;
* In case of previous radiotherapy, at least one measurable lesion should be located outside the irradiated field.
* Ongoing or planned first line treatment with 6 cycles of Xeloda, Eloxatin, and Avastin.
* WHO performance status 0-1 (Karnofsky PS \> 70%);
* Disease evaluation with proven SD, PR or CR according to RECIST after 6 cycles of MTD chemotherapy performed in week 3-4 of the 6th cycle induction therapy, and randomisation performed in week 3-5 of the 6th cycle (see time table);
* Laboratory values obtained ≤ 2 weeks prior to randomisation: adequate bone marrow function (Hb \> 6.0 mmol/L, absolute neutrophil count \> 1.5 x 109/L, platelets \> 100 x 109/L), renal function (serum creatinine ≤ 1.5x ULN and creatinine clearance, Cockroft formula, \> 30 ml/min), liver function (serum bilirubin ≤ 2 x ULN, serum transaminases ≤ 3 x ULN without presence of liver metastases or ≤ 5x ULN with presence of liver metastases);
* Life expectancy \> 12 weeks;
* Age \>= 18 yrs;
* Negative pregnancy test in women with childbearing potential;
* Expected adequacy of follow-up;
* Institutional Review Board approval;
Exclusion Criteria
* Any prior adjuvant treatment after resection of distant metastases
* Previous systemic treatment for advanced disease
At randomisation:
* History or clinical signs/symptoms of CNS metastases;
* History of a second malignancy ≤ 5 years with the exception of adequately treated carcinoma of cervix or basal/squamous cell carcinoma of skin;
* Previous intolerance of XelodaR, EloxatinR, and/or AvastinR for which any of these drugs have been permanently discontinued; patients with previous dose reductions or delays are eligible; patients with grade 2 neurotoxicity after the 6th cycle are eligible, and retreatment with EloxatinR after PFS1 should depend on the grade of neurotoxicity at that moment;
* Known dihydropyrimidine dehydrogenase (DPD) deficiency;
* (Planned) radical resection of all metastatic disease;
* Uncontrolled hypertension, i.e. consistently \> 150/100 mmHg;
* Use of more than 3 antihypertensive drugs;
* Significant cardiovascular disease \< 1 yr before randomisation (symptomatic congestive heart failure, myocardial ischemia or infarction, unstable angina pectoris, serious uncontrolled cardiac arrhythmia, arterial thrombosis, cerebrovascular event, pulmonary embolism);
* Any of these significant cardiovascular events during previous fluoropyrimidine therapy;
* Chronic active infection;
* Any other concurrent severe or uncontrolled disease preventing the safe administration of study drugs;
* Any impairment of gastrointestinal function or -disease that may significantly impair the absorption of oral drugs (i.e. uncontrolled nausea, vomiting, diarrhoea (defined as \>CTC grade 2), malabsorption syndrome, bowel obstruction, or inability to swallow tablets);
* Concomitant treatments: concomitant (or within 4 weeks before randomisation) administration of any other experimental drug under investigation; concurrent treatment with any other anti-cancer therapy; full-dose anticoagulation (is allowed if started during induction therapy);
* Continuous use of immunosuppressive agents (except the use of corticosteroids as anti-emetic prophylaxis/treatment).
18 Years
ALL
No
Sponsors
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Koningin Wilhelmina Fonds
OTHER
Sanofi
INDUSTRY
Hoffmann-La Roche
INDUSTRY
Dutch Colorectal Cancer Group
OTHER
Responsible Party
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Principal Investigators
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C. JA Punt, MD PhD
Role: PRINCIPAL_INVESTIGATOR
Amsterdam Medical Centre, Amsterdam Netherlands
Locations
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University Medical Center Nijmegen
Nijmegen, Gelderland, Netherlands
Countries
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References
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Kurk S, Peeters P, Stellato R, Dorresteijn B, de Jong P, Jourdan M, Creemers GJ, Erdkamp F, de Jongh F, Kint P, Simkens L, Tanis B, Tjin-A-Ton M, Van Der Velden A, Punt C, Koopman M, May A. Skeletal muscle mass loss and dose-limiting toxicities in metastatic colorectal cancer patients. J Cachexia Sarcopenia Muscle. 2019 Aug;10(4):803-813. doi: 10.1002/jcsm.12436. Epub 2019 May 15.
Goey KKH, Elias SG, van Tinteren H, Lacle MM, Willems SM, Offerhaus GJA, de Leng WWJ, Strengman E, Ten Tije AJ, Creemers GM, van der Velden A, de Jongh FE, Erdkamp FLG, Tanis BC, Punt CJA, Koopman M. Maintenance treatment with capecitabine and bevacizumab versus observation in metastatic colorectal cancer: updated results and molecular subgroup analyses of the phase 3 CAIRO3 study. Ann Oncol. 2017 Sep 1;28(9):2128-2134. doi: 10.1093/annonc/mdx322.
Simkens LH, van Tinteren H, May A, ten Tije AJ, Creemers GJ, Loosveld OJ, de Jongh FE, Erdkamp FL, Erjavec Z, van der Torren AM, Tol J, Braun HJ, Nieboer P, van der Hoeven JJ, Haasjes JG, Jansen RL, Wals J, Cats A, Derleyn VA, Honkoop AH, Mol L, Punt CJ, Koopman M. Maintenance treatment with capecitabine and bevacizumab in metastatic colorectal cancer (CAIRO3): a phase 3 randomised controlled trial of the Dutch Colorectal Cancer Group. Lancet. 2015 May 9;385(9980):1843-52. doi: 10.1016/S0140-6736(14)62004-3. Epub 2015 Apr 7.
Related Links
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Dutch Colorectal Cancer Group
Other Identifiers
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CAIRO3
Identifier Type: -
Identifier Source: org_study_id