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Bevacizumab Maintenance Versus no Maintenance After Stop of First-line Chemotherapy in Patients With Metastatic Colorectal Cancer. A Randomized Multicenter Phase III Non-inferiority Trial

Phase 3
18 Years
Open (Enrolling)
Colorectal Cancer

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Trial Information

Bevacizumab Maintenance Versus no Maintenance After Stop of First-line Chemotherapy in Patients With Metastatic Colorectal Cancer. A Randomized Multicenter Phase III Non-inferiority Trial



- To demonstrate that time to progression (TTP) without further treatment is not inferior
to TTP with maintenance therapy comprising bevacizumab in patients with metastatic
colorectal cancer and stable or responding disease after completion of standard
first-line chemotherapy/bevacizumab treatment.


- To evaluate the safety of bevacizumab maintenance therapy in these patients.

- To assess the long-term cost implications of prolonged treatment with bevacizumab.

OUTLINE: This is a multicenter study. Patients are stratified according to best response
during first-line chemotherapy/bevacizumab treatment (complete response and partial response
vs stable disease), duration of first-line treatment (16-20 weeks vs 21-24 weeks), type of
chemotherapy used during first-line treatment (irinotecan and fluoropyrimidine vs
oxaliplatin and fluoropyrimidine vs fluoropyrimidine monotherapy), disease burden (one organ
with metastasis vs more than one organ with metastasis), and by participating center.

- Arm I (bevacizumab maintenance therapy): Patients receive bevacizumab IV over 30
minutes on day 1. Treatment repeats every 21 days in the absence of disease progression
or unacceptable toxicity.

- Arm II (no maintenance therapy): Patients receive no further treatment; they are
monitored for disease progression.

After completion of study therapy or documentation of disease progression, patients are
followed every 3 months for 1 year and then every 6 months for up to 5 years.

Inclusion Criteria


- Histologically or cytologically confirmed metastatic colorectal cancer

- Received prior first-line chemotherapy with oral or intravenous fluoropyrimidine
alone or in combination with irinotecan or oxaliplatin

- Chemotherapy must have been given in combination with a standard dose of
bevacizumab for 16-24 weeks as part of first-line treatment for metastatic
colorectal cancer

- Stable disease, partial response, or complete response after completion of first-line
treatment as documented by abdominal and thoracic CT scan, MRI, or x-ray within the
past 21 days

- No clinical symptoms or history of CNS metastases

- No imaging required in asymptomatic patients


- WHO performance status 0-1

- Serum creatinine < 2.0 mg/dL or 177 μmol/L

- Proteinuria < 2+ by urine dipstick OR urine protein ≤ 1 g by 24-hour urine collection

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 12 months after
completion of study therapy

- Must have basic health insurance with a Swiss health insurance company

- Patients must be compliant and in geographic proximity to allow proper staging and

- No medical reason that prohibits further bevacizumab treatment, including any of the

- Uncontrolled hypertension (systolic blood pressure [BP] > 150 mm Hg and/or
diastolic BP > 100 mm Hg) or clinically significant (i.e., active)
cardiovascular disease

- Serious non-healing wound, active peptic ulcer, or non-healing bone fracture

- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal
abscess within the past 6 months

- History or evidence of inherited bleeding diathesis or coagulopathy with the
risk of bleeding

- No serious underlying medical condition that, in the judgment of the investigator,
could further impair the ability of the patient to participate in the trial (e.g.,
active autoimmune disease or uncontrolled diabetes)

- No psychiatric disorder that would preclude patient understanding of study-related
topics or giving informed consent


- See Disease Characteristics

- At least 4 weeks since prior bevacizumab

- No prior anti-EGFR treatment (e.g., cetuximab) during first-line therapy

- No anticipation of concurrent major surgery (e.g., resection) or ablation of

- No concurrent elective major surgery

- No concurrent daily aspirin exceeding 325 mg/day or clopidogrel exceeding 75 mg/day

- Lower doses of the drugs noted above, or non-steroidal anti-inflammatory drugs
with activity on platelets and gastric mucosa, or dipyridamole are allowed if
given at a stable dose for ≥ 2 weeks prior to study entry

- No other concurrent experimental drugs or anticancer therapy

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Time to progression

Outcome Time Frame:

From randomization until documented progressive disease or death due to tumor.

Safety Issue:


Principal Investigator

Dieter Koeberle, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Kantonsspital St. Gallen


Switzerland: Swissmedic

Study ID:

SAKK 41/06



Start Date:

October 2007

Completion Date:

December 2017

Related Keywords:

  • Colorectal Cancer
  • stage IV colon cancer
  • stage IV rectal cancer
  • Colorectal Neoplasms