A randomized, open-label Phase III study to assess efficacy and safety of bevacizumab in combination with capecitabine as first line treatment for elderly patients with metastatic colorectal cancer - AVEX: Avastin in Elderly with Xeloda

Conditions: First line metastatic colorectal carcinoma
MedDRA version: 8.1Level: LLTClassification code 10052358Term: Colorectal cancer metastatic

Registration Number: EUCTR2006-003293-10-PL

Lead Sponsor: F. Hoffmann-La Roche Ltd.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 430

Inclusion Criteria

1) Written informed consent (approved by the Institutional Review Board [IRB] / Independent Ethics Committee [IEC]) obtained prior to any study specific screening procedures
2) Age >= 70 years
3) Patient must be able to comply with the protocol
4) Histologically or cytologically confirmed carcinoma of the colon and/or rectum with evidence of metastases (new confirmation of metastatic disease is required in case the time interval from last histological/cytological diagnosis to enrolment exceeds 3 years)
5) Diagnosis of metastatic disease not more than 6 months prior to enrolment
6) At least one measurable metastatic lesion, measurable or at least evaluable disease (as per RECIST criteria)
7) Prior adjuvant (or neo-adjuvant for rectal cancer patients) chemotherapy allowed if completed more than 6 months before inclusion
8) ECOG performance score of 0 – 2
9) Life Expectancy of at least 3 months
10) Adequate haematological function: ANC >= 1.5 x 10Exp9/L; platelets >= 100 x 10Exp9/L, Hb >= 9 g/dL
11) INR <= 1.5; PTT <= 1.5 × ULN within 7 days prior to starting study treatment
12) Adequate liver function: Serum bilirubin <= 1.5 x ULN; AST / ALP <= 2.5 x ULN (in case of liver metastases < 5 × ULN)
13) Calculated creatinine clearance >= 50 mL/min
14) Urine dipstick for proteinuria < 2+. If urine dipstick is >= 2+, 24-hour urine must demonstrate <= 1 g of protein in 24 hours

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
;
1) Written informed consent (approved by the Institutional Review Board [IRB] / Independent Ethics Committee [IEC]) obtained prior to any study specific screening procedures
2) Age >= 70 years
3) Patient must be able to comply with the protocol
4) Histologically or cytologically confirmed carcinoma of the colon and/or rectum with evidence of metastases (new confirmation of metastatic disease is required in case the time interval from last histological/cytological diagnosis to enrolment exceeds 3 years)
5) Diagnosis of metastatic disease not more than 6 months prior to enrolment
6) At least one measurable metastatic lesion, measurable or at least evaluable disease (as per RECIST criteria)
7) Prior adjuvant (or neo-adjuvant for rectal cancer patients) chemotherapy allowed if completed more than 6 months before inclusion
8) ECOG performance score of 0 – 2
9) Life Expectancy of at least 3 months
10) Adequate haematological function: ANC >= 1.5 x 10Exp9/L; platelets >= 100 x 10Exp9/L, Hb >= 9 g/dL
11) INR <= 1.5; PTT <= 1.5 × ULN within 7 days prior to starting study treatment
12) Adequate liver function: Serum bilirubin <= 1.5 x ULN; AST / ALP <= 2.5 x ULN (in case of liver metastases < 5 × ULN)
13) Calculated creatinine clearance >= 50 mL/min
14) Urine dipstick for proteinuria < 2+. If urine dipstick is >= 2+, 24-hour urine must demonstrate <= 1 g of protein in 24 hours

Exclusion Criteria

1) Patients who received adjuvant antiVEGF treatment
2) Prior chemotherapeutic treatment for metastatic CRC
3) Clinical evidence of brain metastases or history or evidence upon physical examination of CNS disease unless adequately treated (e.g., seizure not controlled with standard medical therapy or history of stroke) or psychiatric disability judged by the investigator to be clinically significant precluding informed consent or interfering with compliance for oral drug intake
4) Past or current history (within the last 5 years prior to treatment start) of other malignancies except metastatic colorectal cancer (Patients with curatively treated basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix are eligible)
5) Clinically significant cardiovascular disease, for example CVA (<= 6 months before treatment start), myocardial infarction (<= 6 months before treatment start), unstable angina, NYHA >= grade 2 CHF, arrhythmia requiring medication, or uncontrolled hypertension
6) Treatment with any other investigational agent, or participation in another clinical trial within 30 days prior to entering this study
7) Known hypersensitivity to any of the study drugs
8) Current or recent (within 10 days of first dose of study treatment) daily use of aspirin (> 325 mg/day) or other NSAID
9) Current or recent (within 10 days prior to study treatment start) use of full-dose oral or parenteral anticoagulants or thrombolytic agent for therapeutic (as opposed to prophylactic) purposes. Patients receiving (or considered candidate to receive) anticoagulants agents as prophylaxis of cardiovascular risk, should continue (or start) the appropriate treatment at study entry
10) History of thromboembolic or haemorrhagic events within 6 months prior to treatment
11) History of abdominal fistula, gastrointestinal perforation or intraabdominal abscess within 6 month prior to enrolment
12) Evidence of bleeding diathesis or coagulopathy
13) Serious, non healing wound, ulcer, or bone fracture
14) Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to treatment
15) Evidence of any other disease, metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or puts the patient at high risk for treatment-related complications (e.g. serious intercurrent infections, other serious uncontrolled concomitant disease)
16) Patients who don’t have an intact GI (e.g. clinically significant malabsorption syndrome) and those who are unable to take oral medication (e.g. swallowing difficulty)
17) Men of childbearing potential not willing to use effective means of contraception
18) Requirement for concurrent use of the antiviral agent sorivudine or chemically related analogues, such as brivudine
19) Organ allografts requiring immunosuppressive therapy

;
1) Patients who received adjuvant antiVEGF treatment
2) Prior chemotherapeutic treatment for metastatic CRC
3) Clinical evidence of brain metastases or history or evidence upon physical examination of CNS disease unless adequately treated (e.g., seizure not controlled with standard medical therapy or history of stroke) or psychiatric disability judged by the investigator to be clinically significant precluding informed consent or interfering with compliance for oral drug intake
4) Past or current history (within the last 5 years prior to treatment start) of other malignancies except metastatic colorectal cancer (Patients with curatively treated basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix are eligible)
5) Clinically significant cardiovascular disease, for example CVA (<= 6 months before treatment start), myocardial infarction (<= 6 months before treatment start), unstable angina, NYHA >= grade 2 CHF, arrhythmia requiring medication, or uncontrolled hypertension
6) Treatment with any other investigational agent, or participation in another clinical trial within 30 days prior to entering this study
7) Known hypersensitivity to any of the study drugs
8) Current or recent (within 10 days of first dose of study treatment) daily use of aspirin (> 325 mg/day) or other NSAID
9) Current or recent (within 10 days prior to study treatment start) use of full-dose oral or parenteral anticoagulants or thrombolytic agent for therapeutic (as opposed to prophylactic) purposes. Patients receiving (or considered candidate to receive) anticoagulants agents as prophylaxis of cardiovascular risk, should continue (or start) the appropriate treatment at study entry
10) History of thromboembolic or haemorrhagic events within 6 months prior to treatment
11) History of abdominal fistula, gastrointestinal perforation or intraabdominal abscess within 6 month prior to enrolment
12) Evidence of bleeding diathesis or coagulopathy
13) Serious, non healing wound, ulcer, or bone fracture
14) Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to treatment
15) Evidence of any other disease, metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or puts the patient at high risk for treatment-related complications (e.g. serious intercurrent infections, other serious uncontrolled concomitant disease)
16) Patients who don’t have an intact GI (e.g. clinically significant malabsorption syndrome) and those who are unable to take oral medication (e.g. swallowing difficulty)
17) Men of childbearing potential not willing to use effective means of contraception
18) Requirement for concurrent use of the antiviral agent sorivudine or chemically related analogues, such as brivudine
19) Organ allografts requiring immunosuppressive therapy

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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