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 the Elderly with Xeloda
- Conditions
- First line metastatic colorectal carcinomaMedDRA version: 8.1Level: LLTClassification code 10052358Term: Colorectal cancer metastatic
- Registration Number
- EUCTR2006-003293-10-AT
- Lead Sponsor
- F. Hoffmann-La Roche Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 280
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 histological/cytological confirmation of diagnosis is required in case the time interval from last histological/cytological diagnosis to starting study treatment exceeds 3 years)
5) Diagnosis of metastatic disease not more than 6 months prior to starting study treatment. Patient with relapsed metastatic disease after a R0 resection of liver metastases will also be eligible providing that the relapse was diagnosed not more than 6 months prior to starting study treatment.
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 starting study treatment.
8) ECOG performance score of 0 – 2 (see Appendix 4)
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 within 7 days prior to starting study treatment
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) within 7 days prior to starting study treatment
13) Calculated creatinine clearance >= 30 mL/min (measured using the Cockroft and Gault formula, see Appendix 7) within 7 days prior to starting study treatment.
14) Urine dipstick for proteinuria < 2+. If urine dipstick is >= 2+, 24-hour urine must demonstrate <= 1 g of protein in 24 hours within 7 days prior to starting study treatment.
15) Patients with metastatic colorectal cancer, not candidates for curative resection of metastatic lesions and not optimal candidates for a combination chemotherapy including irinotecan or oxaliplatin
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 histological/cytological confirmation of diagnosis is required in case the time interval from last histological/cytological diagnosis to starting study treatment exceeds 3 years)
5) Diagnosis of metastatic disease not more than 6 months prior to starting study treatment. Patient with relapsed metastatic disease after a R0 resection of liver metastases will also be eligible providing that the relapse was diagnosed not more than 6 months prior to starting study treatment.
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 starting study treatment.
8) ECOG performance score of 0 – 2 (see Appendix 4)
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 within 7 days prior to starting study treatment
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) within 7 days prior to starting study treatment
13) Calculated creatinine clearance >= 30 mL/min (measured using the Cockroft and Gault formula, see Appendix 7) within 7 days prior to starting study treatment.
14) Urine dipstick for proteinuria < 2+. If urine dipstick is >= 2+, 24-hour urine must demonstrate <= 1 g of protein in 24 hours within 7 days prior to starting study treatment.
15) Patients with metastatic colorectal cancer, not candidates for curative resection of metastatic lesions and not optimal candidates for a combination chemotherapy including irinotecan or oxaliplatin
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) 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 starting study treatment) 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 starting study treatment), myocardial infarction (<= 6 months before starting study treatment), unstable angina, NYHA >= grade 2 CHF, arrhythmia requiring medication, or uncontrolled hypertension
6) Patients must not have received treatment with any other investigational agent within 30 days prior to starting study treatment.
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 starting study treatment
11) History of abdominal fistula, gastrointestinal perforation or intraabdominal abscess within 6 month prior to starting study treatment
12) Evidence of clinical significant 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 starting study 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) Male patients, with partners of childbearing potential who are not willing to use effective means of contraception whilst on treatment and for 90 days after last dose of the study drug.
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 starting study treatment) 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 starting study treatment), myocardial infarction (<= 6 months before starting study treatment), unstable angina, NYHA >= grade 2 CHF, arrhythmia requiring medication, or uncontrolled hypertension
6) Patients must not have received treatment with any other investigational agent within 30 days prior to starting study treatment.
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 starting study treatment
11) History of abdominal fistula, gastrointestinal perforation or intraabdominal abscess within 6 month prior to starting study treatment
12) Evidence of clinical significant 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 starting study 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) Male patients, with partners of childbearing potential who are not willing to use effective means of contraception whilst on treatment and for 90 days after last dose of the study drug.
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