Maintenance Treatment Versus Observation After Induction in Advanced Colorectal Carcinoma (CAIRO3)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Koningin Wilhelmina Fonds
Sanofi
Hoffmann-La Roche
Information provided by (Responsible Party):
Dutch Colorectal Cancer Group
ClinicalTrials.gov Identifier:
NCT00442637
First received: February 28, 2007
Last updated: December 11, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
Colorectal Cancer Metastatic
Drug: capecitabine + bevacizumab
Other: observation
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Dutch Colorectal Cancer Group:

Primary Outcome Measures:
  • Progression-free survival after re-introduction of MTD chemotherapy and bevacizumab (PFS2) [ Time Frame: study duration ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression-free survival between observation versus maintenance therapy (PFS1) [ Time Frame: study duration ] [ Designated as safety issue: No ]
  • Response rate during re-introduction of MTD chemotherapy and bevacizumab [ Time Frame: study duration ] [ Designated as safety issue: No ]
  • Toxicity [ Time Frame: study duration ] [ Designated as safety issue: Yes ]
  • Quality of life [ Time Frame: study duration ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: study duration ] [ Designated as safety issue: No ]
  • Translational research [ Time Frame: study duration ] [ Designated as safety issue: No ]

Estimated Enrollment: 635
Study Start Date: January 2007
Estimated Study Completion Date: December 2013
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
observation
Other: observation
observation after induction treatment
Active Comparator: 2
capecitabine plus bevacizumab
Drug: capecitabine + bevacizumab
Ca 1250 mg/m2 daily orally continuously, B 7.5 mg/kg i.v. q 3 w

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Before the start of induction therapy:

Inclusion Criteria:

  • 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.

Exclusion criteria

  • 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:

Inclusion criteria:

  • 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;
  • 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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00442637

Locations
Netherlands
University Medical Center Nijmegen
Nijmegen, Gelderland, Netherlands
Sponsors and Collaborators
Dutch Colorectal Cancer Group
Koningin Wilhelmina Fonds
Sanofi
Hoffmann-La Roche
Investigators
Principal Investigator: C. JA Punt, MD PhD Amsterdam Medical Centre, Amsterdam Netherlands
  More Information

Additional Information:
No publications provided

Responsible Party: Dutch Colorectal Cancer Group
ClinicalTrials.gov Identifier: NCT00442637     History of Changes
Other Study ID Numbers: CAIRO3
Study First Received: February 28, 2007
Last Updated: December 11, 2013
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Dutch Colorectal Cancer Group:
CAIRO3
DCCG
colorectal cancer
induction
metronomic chemotherapy
observation
capecitabine
bevacizumab
oxaliplatin

Additional relevant MeSH terms:
Colorectal Neoplasms
Colonic Diseases
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms
Neoplasms by Site
Rectal Diseases
Bevacizumab
Capecitabine
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Growth Inhibitors
Growth Substances
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014