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Study Summary
No. 2004-0826:.......Colon......Milind Javle......Gastrointestinal Medical Oncology
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Study Summary Title
Study Summary
Number:
2004-0826
Study Title:A Randomized, Three Arm Multinational Phase III Study to Investigate Bevacizumab (q3w or q2w) in Combination with Either Intermittent Capecitabine Plus Oxaliplatin ("XELOX") (q3w) or Fluorouracil/Leucovorin with Oxaliplatin ("FOLFOX-4") Versus "FOLFOX-4" Regimen Alone as Adjuvant Chemotherapy in Colon Carcinoma (BO 17920)
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Physician New Patient Referral
Name:Milind JavlePatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:Gastrointestinal Medical OncologyReferring MD
Call:
800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-792-2828
Contact us about clinical trials
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General Information
Disease Group:ColonSupported By:N/A
Phase of Study:Phase IIIReturn
Visit:
Arm A and B every 2 weeks, Arm C every 3 weeks.
Treatment
Agents:
5-Fluorouracil
Bevacizumab
Calcium Leucovorin
Capecitabine
Oxaliplatin
Home Care:Study tests and evaluations will be performed at MDACC.
Treatment Loc:Independent Multicenter Arrangements
Estimated
Length of Stay
in Houston:
Hospitalization is not required.
Description/
Intervention:
The goal of this clinical research study is to find out if adding Avastin
(bevacizumab) to the chemotherapy treatments FOLFOX-4 [5-fluorouracil (5-FU),
leucovorin (LV), and Eloxatin (oxaliplatin)] or XELOX (capecitabine plus
oxaliplatin) can help to decrease the chance of colon cancer returning in
patients who have had surgery to remove it. The study also will look at the
side effects of these different treatments.
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Study Objectives / Outcomes
Primary objectives of the study were:
1. To demonstrate that the combination of bevacizumab and FOLFOX-4 is superior to FOLFOX-4 alone in terms of disease-free survival in chemotherapy-naive patients who underwent surgery with curative intent for colon carcinoma.
2. To demonstrate that the combination of bevacizumab and XELOX is superior to FOLFOX-4 alone in terms of disease-free survival in chemotherapy-naive patients who underwent surgery with curative intent for colon carcinoma.

In case both primary objectives were achieved, one secondary objective was to further investigate if the combination of bevacizumab and XELOX is at least as efficacious as the combination of bevacizumab and FOLFOX-4 in terms of diseasefree survival and overall survival.

The primary efficacy analysis (cut-off date: 30th June 2010) showed that the study did not meet the co-primary objectives of prolonging disease-free survival in stage III colon carcinoma patients.


Secondary objectives:
  • To further follow-up patients in terms of overall survival.
  • To further evaluate and compare the safety profiles of the treatment groups.
  • To evaluate the immunogenicity of bevacizumab measured as induction of HAHA (completed with the primary efficacy analysis).


Tertiary objectives:
  • To evaluate and compare medical care utilization in the three treatment groups.
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Study Status Information
Study Activation / Registration Date:06/09/2005
IRB Review and Approval Date:01/19/2005
Study Type:Phase Iii
Recruitment Status:Closed
Projected Accrual:3450
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Enrollment Eligibility
If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:1) Signed written informed consent obtained prior to any study specific screening procedures.

2) Patient must be willing and able to comply with the protocol.

3) Age >/= 18.

4) Histologically confirmed colon carcinoma, AJCC/UICC Stage II or Stage III defined as a tumour location >/= 15cm from the anal verge by endoscopy or above the peritoneal reflection at surgery. The patient must not be a candidate for (neo) adjuvant radiotherapy.

5) NOTE: Stage II patients have to be considered as high-risk patients fulfilling one of the following criteria: T4 tumours; patients presenting with bowel obstruction or perforation; histological signs of vascular invasion (i.e. blood and lymphatic vessels) or perineural invasion; patients aged less than 50 years; patients with sub-optimal surgery (less than 12 nodes analyzed).

6) Curative surgery not less than 4 and not more than 8 weeks prior to randomization.

7) ECOG performance status 0 or 1.

8) Life expectancy of >/= 5 years.

Exclusion Criteria:1) Macroscopic or microscopic evidence of remaining tumour. Patients should never have had any evidence of metastatic disease (including presence of tumour cells in the ascites). The isolated finding of cytokeratin positive cells in bone marrow is not considered evidence of metastatic disease for purposes of this study.

2) Carcinoembryonic antigen > 1.5 x ULN after surgery (during screening period).

3) For patients with colostomy, unwilling to delay revision until at least 28 days after treatment completion.

4) Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study treatment start, not fully healed wounds, or anticipation of the need for major surgical procedure during the course of the study. Central venous access device (CVAD) for chemotherapy administration must be inserted at least 2 days prior to treatment start.

5) Previous anti-angiogenic treatment for any malignancy; cytotoxic chemotherapy, radiotherapy or immunotherapy for colon cancer.

6) Other malignancies within the last 5 years (other than curatively treated basal cell carcinoma of the skin and/or in situ carcinoma of the cervix).

7) Females with a positive or no pregnancy test (within 7 days before treatment start) unless childbearing potential can be otherwise excluded (postmenopausal i.e. amenorrheic for at least 2 years, hysterectomy or oophorectomy).

8) Lactating women.

9) Fertile women (<2 years after last menstruation) and men of childbearing potential not willing to use effective means of contraception.

10) History or evidence upon physical examination of CNS disease (e.g., primary brain tumour, seizure not controlled with standard medical therapy, any brain metastases).

11) History of psychiatric disability judged by the investigator to be clinically significant, precluding informed consent or interfering with compliance for oral drug intake.

12) Clinically significant (i.e. active) cardiovascular disease. This includes, but is not limited to, the following examples: cerebrovascular accidents (</= 6 months prior to randomisation), myocardial infarction (</= 1 year prior to randomisation), uncontrolled hypertension (>140/90 mmHg) while receiving chronic medication, unstable angina, New York Heart Association (NYHA) Grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication, clinically significant ECG findings (e.g. QTc ≥ 440 msecs [male] 460 msecs [female] or >/= 2º AV Block, etc.).

13) Continued from Exclusion #12: Patients with pacemakers are allowed to enter the study only if they are considered as being in a stable condition. In case of doubt, the investigator should obtain a consultation with a local cardiologist. Lack of physical integrity of the upper gastro-intestinal tract, malabsorption syndrome, or inability to take oral medication.

14) Interstitial pneumonia or extensive symptomatic fibrosis of the lungs.

15) Known peripheral neuropathy >/= CTCAE v 3.0 Grade 1. Absence of deep tendon reflexes (DTRs) as the sole neurological abnormality does not render the patient ineligible.

16) Organ allografts requiring immunosuppressive therapy.

17) Serious, non-healing wound, ulcer, or bone fracture.

18) Evidence of bleeding diathesis or coagulapathy.

19) Current or recent (within 10 days prior to study treatment start) use of full-dose oral or parenteral anticoagulants or thrombolytic agent for therapeutic purposes.

20) Chronic, daily treatment with high-dose aspirin (>325mg/day) or clopidogrel (> 75 mg/day).

21) Chronic treatment with corticosteroids (dose of >/= 10 mg/day methylprednisolone equivalent) (excluding inhaled steroids).

22) Serious intercurrent infections (uncontrolled or requiring treatment).

23) Known dihydropyrimidine dehydrogenase (DPD) deficiency.

24) Current or recent (within the 28 days prior to randomization) treatment with another investigational drug or participation in another investigation study.

25) Patients with known allergy to Chinese hamster ovary cell proteins or other recombinant human or humanized antibodies or any excipients of bevacizumab formulation, platinum compounds or to any other components of the study drugs.

26) History or presence of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug or patient at high risk from treatment complications.

27) Presence of proteinuria at baseline as defined by: Patients with > 1g of protein/24 hr by a 24-hour urine collection.

28) Any laboratory values at baseline are as follows: Haematology - Absolute neutrophil count (ANC) < 1.5 x 10^9/L; Platelet count < 100 x 10^9/L; Haemoglobin < 9 g/dL (may be transfused to maintain or exceed this level); International Normalized Ratio (INR) > 1.5; APTT >/=1.5 x Upper Limit of Normal (ULN). Biochemistry - Total bilirubin > 1.5 x ULN; AST, ALT > 2.5 x ULN; Alkaline phosphatase > 2.5 xULN; Serum Creatinine > 1.5 x ULN or creatinine clearance </= 50 mL/min (e.g.Cockroft and Gault formula).

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Links
Registration Number: NCT00112918
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
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Results


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