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Colorectal Cancer MetastaticPhase 3CAIRO3NCT00442637

Maintenance Treatment Versus Observation After Induction in Advanced Colorectal Carcinoma

A Phase 3 study testing capecitabine + bevacizumab and observation in people with Colorectal Cancer Metastatic, run by Dutch Colorectal Cancer Group at 1 site in Netherlands.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

The optimal duration of systemic treatment in patients with advanced colorectal cancer is unknown. 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Colorectal Cancer Metastatic
What is being tested?
capecitabine + bevacizumab and observation
Could I receive a placebo?
No, everyone receives an active treatment
How many people
635 participants
Where
1 siteNetherlands
Study dates
Jan 2007to Dec 2013
Phase
Phase 3
Are there results?
None posted in the registry

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 proof of colorectal cancer (in case of a single metastasis, histological or cytological proof of this lesion should be obtained);
  • 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%);
Show all 28Show fewer
  • 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;
  • Written informed consent Exclusion criteria
  • 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).

Who cannot join

  • Prior adjuvant treatment for stage II/III colorectal cancer ending within 6 months before the start of induction treatment
  • Any prior adjuvant treatment after resection of distant metastases
  • Previous systemic treatment for advanced disease
  • At randomisation:

Trial locations and contacts

1 site in 1 country.

Netherlands1 site

  • University Medical Center Nijmegen

    Nijmegen, Gelderland

Other trials in Netherlands

About this study

Official title: Maintenance Treatment With Capecitabine and Bevacizumab Versus Observation After Induction Treatment With Chemotherapy and Bevacizumab as First-line Treatment in Patients With Advanced Colorectal Carcinoma

The optimal duration of systemic treatment in patients with advanced colorectal cancer is unknown.

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.

Read the detailed description

Standard 1st-line treatment for patients with advanced colorectal cancer currently consists of chemotherapy plus bevacizumab. With this approach the median overall survival is approximately 20 months, and progression-free survival in first-line approximately 9-11 months. The optimal duration of treatment is unknown. Current data suggest that the efficacy of bevacizumab is dependent on concomitant use of chemotherapy. However, oxaliplatin almost invariably gives rise to neuropathy after 6-8 cycles. Prolonged use of capecitabine is associated with e.g. hand-foot syndrome. Lastly, the prolonged use of these agents is associated with considerable costs.

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.

Being tested
capecitabine + bevacizumab, observation
Keywords
CAIRO3, DCCG, colorectal cancer, induction, metronomic chemotherapy, observation, capecitabine, bevacizumab, oxaliplatin
Medical subject headings
Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • capecitabine + bevacizumabDrug

    Ca 1250 mg/m2 daily orally continuously, B 7.5 mg/kg i.v. q 3 w

  • observationOther

    observation after induction treatment

Study groups in NCT00442637
Study groupRoleWhat they receive
1Experimentalobservation
Receives: Other: observation
2Active comparatorcapecitabine plus bevacizumab
Receives: Drug: capecitabine + bevacizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression-free survival after re-introduction of MTD chemotherapy and bevacizumab (PFS2)

    Measured: study duration

Secondary outcomes (6)

  1. Progression-free survival between observation versus maintenance therapy (PFS1)

    Measured: study duration

  2. Response rate during re-introduction of MTD chemotherapy and bevacizumab

    Measured: study duration

  3. Toxicity

    Measured: study duration

  4. Quality of life

    Measured: study duration

  5. Overall survival

    Measured: study duration

  6. Translational research

    Measured: study duration

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Mar 2007 (estimated)
  2. Study startJan 2007
  3. Primary completionSep 2013
  4. Study completionDec 2013 (estimated)

Resources

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
635 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00442637
Sponsor's protocol ID
CAIRO3
Acronym
CAIRO3
Status last verified
Dec 2013
First submitted
28 Feb 2007
Last updated
12 Dec 2013
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 31094083

  • 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.

    PubMed 28911067

  • 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.

    PubMed 25862517

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing capecitabine + bevacizumab and observation in people with Colorectal Cancer Metastatic, run by Dutch Colorectal Cancer Group at 1 site in Netherlands.

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 28 inclusion and 4 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: status not confirmed, as of the sponsor's last update on 12 Dec 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Netherlands. 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.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

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?

Progression-free survival after re-introduction of MTD chemotherapy and bevacizumab (PFS2) (time frame: study duration). 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 NCT00442637, which also lists 3 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 12 Dec 2013.

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