Maintenance Treatment Versus Observation After Induction in Advanced Colorectal Carcinoma

• Status: Unknown status
• Trial end date: 2013-12-01
• Target enrollment: 0
• Participant gender: All

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 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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Dutch Colorectal Cancer Group
• Collaborators: Hoffmann-La Roche; Koningin Wilhelmina Fonds; Sanofi
• Treatments: Bevacizumab; Capecitabine

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).