Evaluation of Bevacizumab in Combination With First-Line Chemotherapy in Patients Aged 75 Years of Older With Metastatic Colorectal Adenocarcinoma (Prodige20) (Prodige20)
Primary Purpose
Metastatic Colorectal Adenocarcinoma
Status
Completed
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
LV5FU2 simplified, FOLFOX 4 simplified, FOLFIRI modified
LV5FU2 simplified,FOLFOX 4 simplified, FOLFIRI modified, Bevacizumab 5 mg/kg/ 2 weeks
Sponsored by
About this trial
This is an interventional other trial for Metastatic Colorectal Adenocarcinoma
Eligibility Criteria
Inclusion Criteria:
- Patients aged 75 years or older
- ECOG ≤2
- histologically proven unresectable metastatic colorectal adenocarcinoma
- Measurable lesion according to RECIST criteria
- Absence of prior chemotherapy for metastatic disease. Adjuvant chemotherapy following resection of the primary tumor is authorized if completed more than 6 months previously
- Patients treated with anticoagulants (coumadin, warfarin) can be included if close surveillance of the INR can be ensured. A change to low-molecular-weight heparin is preferable as long as the indications are respected
- Completed geriatric self-questionnaire
- Completed "Team" geriatric questionnaire (including Spitzer QoL Index)
- Written informed consent
Exclusion Criteria:
- Estimated life expectancy < 3 months
- Non-resolved intestinal occlusion or sub-occlusion
- Cerebral metastasis
- Other evolutive malignant tumor (non-stabilized cancer for less than 2 years)
- Evolutive gastroduodenal ulcer, wound or bone fracture
- Active heart disease: uncontrolled hypertension, myocardial infarction In the previous 6 months, angina, non-compensated congestive heart failure
- Major surgery, except for biopsy, or irradiation in the 4 weeks preceding the start of treatment
- Polynuclear neutrophils <1500/mm3, platelets <100 000/mm3 or 24-h proteinuria > 1g
- History of arterial thromboembolic event (cerebrovascular accident, transient ischemic attack, subarachnoid hemorrhage) in the 12 months preceding the first dose of bevacizumab
- History of distal or visceral ischemia ≥ grade 2 in the 12 months preceding the first dose of bevacizumab
- History of life-threatening pulmonary embolism in the 6 months preceding the first dose of bevacizumab
- Impossibility to ensure regular follow-up
Sites / Locations
- CHU de Dijon
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
chimiotherapy alone
chemiotherapy + bevacizumab 5 mg/kg/ 2 weeks
Arm Description
LV5FU2 simplified, 5-fluorouracil/leucovorin with oxaliplatin 4 (FOLFOX) simplified, fluorouracil, leucovorin, and irinotecan(FOLFIRI) modified.
LV5FU2 simplified, FOLFOX 4 simplified, FOLFIRI modified. Bevacizumab 5 mg/kg/ 2 weeks
Outcomes
Primary Outcome Measures
Initial examination
thoraco-abdomino-pelvic tomodensitometry or thoracic tomodensitometry and abdomino-pelvic MRI with identification and measurement of the target tumors according to RECIST (Response Evaluation Criteria in Solid Tumors
)criteria.
Secondary Outcome Measures
Initial examination
Medical history, clinical examination (HR, arterial blood pressure
, temperature, weight, height, Eastern Cooperative Oncology Group performance status),
measurement of body surface area, ECG
completion of questionnaire by the patient (annexe 1),
completion of geriatric questionnaire "team" (annexe 2)
biological examination including:
full blood count-platelets
blood electrolyte panel, creatinemia
Albumin
ASAT, ALAT, PAL, GGT, total and conjugated bilirubin
CEA, CA 19.9, LDH markers
balanced INR for patients on AVK
Urinary dip with 24-hour proteinuria if > 1+
Measurement of creatinine clearance using the Cockcroft formula (in men: (140-age) x weight (kg)/0.814 x creatinemia (μmol), in women: (140-age) x weight (kg)/0.85 x creatinemia (μmol)),
In the absence of a cardiological examination in the year before or in the case of a history of severe cardiovascular disease: consultation in cardiology.
Full Information
NCT ID
NCT01900717
First Posted
July 12, 2013
Last Updated
December 26, 2018
Sponsor
Centre Hospitalier Universitaire Dijon
1. Study Identification
Unique Protocol Identification Number
NCT01900717
Brief Title
Evaluation of Bevacizumab in Combination With First-Line Chemotherapy in Patients Aged 75 Years of Older With Metastatic Colorectal Adenocarcinoma (Prodige20)
Acronym
Prodige20
Official Title
Evaluation of Bevacizumab in Combination With First-Line Chemotherapy in Patients Aged 75 Years of Older With Metastatic Colorectal Adenocarcinoma
Study Type
Interventional
2. Study Status
Record Verification Date
December 2018
Overall Recruitment Status
Completed
Study Start Date
July 2011 (Actual)
Primary Completion Date
May 2015 (Actual)
Study Completion Date
March 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Centre Hospitalier Universitaire Dijon
4. Oversight
5. Study Description
Brief Summary
To evaluate tolerance to and efficacy of bevacizumab in the treatment of MCRC in elderly patients, we propose a phase II randomised study comparing a chemotherapy + bevacizumab arm with a chemotherapy alone arm in the first-line treatment of MCRC in patients aged 75 years and older.
This study is destined to continue as a phase III trial if both arms meet the selection criteria to show or not the benefits of treatment with bevacizumab combined with chemotherapy.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Colorectal Adenocarcinoma
7. Study Design
Primary Purpose
Other
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
102 (Actual)
8. Arms, Groups, and Interventions
Arm Title
chimiotherapy alone
Arm Type
Active Comparator
Arm Description
LV5FU2 simplified,
5-fluorouracil/leucovorin with oxaliplatin 4 (FOLFOX) simplified,
fluorouracil, leucovorin, and irinotecan(FOLFIRI) modified.
Arm Title
chemiotherapy + bevacizumab 5 mg/kg/ 2 weeks
Arm Type
Experimental
Arm Description
LV5FU2 simplified,
FOLFOX 4 simplified,
FOLFIRI modified.
Bevacizumab 5 mg/kg/ 2 weeks
Intervention Type
Drug
Intervention Name(s)
LV5FU2 simplified, FOLFOX 4 simplified, FOLFIRI modified
Intervention Type
Drug
Intervention Name(s)
LV5FU2 simplified,FOLFOX 4 simplified, FOLFIRI modified, Bevacizumab 5 mg/kg/ 2 weeks
Primary Outcome Measure Information:
Title
Initial examination
Description
thoraco-abdomino-pelvic tomodensitometry or thoracic tomodensitometry and abdomino-pelvic MRI with identification and measurement of the target tumors according to RECIST (Response Evaluation Criteria in Solid Tumors
)criteria.
Time Frame
21 days before the first course of treatment
Secondary Outcome Measure Information:
Title
Initial examination
Description
Medical history, clinical examination (HR, arterial blood pressure
, temperature, weight, height, Eastern Cooperative Oncology Group performance status),
measurement of body surface area, ECG
completion of questionnaire by the patient (annexe 1),
completion of geriatric questionnaire "team" (annexe 2)
biological examination including:
full blood count-platelets
blood electrolyte panel, creatinemia
Albumin
ASAT, ALAT, PAL, GGT, total and conjugated bilirubin
CEA, CA 19.9, LDH markers
balanced INR for patients on AVK
Urinary dip with 24-hour proteinuria if > 1+
Measurement of creatinine clearance using the Cockcroft formula (in men: (140-age) x weight (kg)/0.814 x creatinemia (μmol), in women: (140-age) x weight (kg)/0.85 x creatinemia (μmol)),
In the absence of a cardiological examination in the year before or in the case of a history of severe cardiovascular disease: consultation in cardiology.
Time Frame
14 days before inclusion
10. Eligibility
Sex
All
Minimum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients aged 75 years or older
ECOG ≤2
histologically proven unresectable metastatic colorectal adenocarcinoma
Measurable lesion according to RECIST criteria
Absence of prior chemotherapy for metastatic disease. Adjuvant chemotherapy following resection of the primary tumor is authorized if completed more than 6 months previously
Patients treated with anticoagulants (coumadin, warfarin) can be included if close surveillance of the INR can be ensured. A change to low-molecular-weight heparin is preferable as long as the indications are respected
Completed geriatric self-questionnaire
Completed "Team" geriatric questionnaire (including Spitzer QoL Index)
Written informed consent
Exclusion Criteria:
Estimated life expectancy < 3 months
Non-resolved intestinal occlusion or sub-occlusion
Cerebral metastasis
Other evolutive malignant tumor (non-stabilized cancer for less than 2 years)
Evolutive gastroduodenal ulcer, wound or bone fracture
Active heart disease: uncontrolled hypertension, myocardial infarction In the previous 6 months, angina, non-compensated congestive heart failure
Major surgery, except for biopsy, or irradiation in the 4 weeks preceding the start of treatment
Polynuclear neutrophils <1500/mm3, platelets <100 000/mm3 or 24-h proteinuria > 1g
History of arterial thromboembolic event (cerebrovascular accident, transient ischemic attack, subarachnoid hemorrhage) in the 12 months preceding the first dose of bevacizumab
History of distal or visceral ischemia ≥ grade 2 in the 12 months preceding the first dose of bevacizumab
History of life-threatening pulmonary embolism in the 6 months preceding the first dose of bevacizumab
Impossibility to ensure regular follow-up
Facility Information:
Facility Name
CHU de Dijon
City
Dijon
ZIP/Postal Code
21079
Country
France
12. IPD Sharing Statement
Citations:
PubMed Identifier
31101691
Citation
Dohan A, Gallix B, Guiu B, Le Malicot K, Reinhold C, Soyer P, Bennouna J, Ghiringhelli F, Barbier E, Boige V, Taieb J, Bouche O, Francois E, Phelip JM, Borel C, Faroux R, Seitz JF, Jacquot S, Ben Abdelghani M, Khemissa-Akouz F, Genet D, Jouve JL, Rinaldi Y, Desseigne F, Texereau P, Suc E, Lepage C, Aparicio T, Hoeffel C; PRODIGE 9 Investigators and PRODIGE 20 Investigators. Early evaluation using a radiomic signature of unresectable hepatic metastases to predict outcome in patients with colorectal cancer treated with FOLFIRI and bevacizumab. Gut. 2020 Mar;69(3):531-539. doi: 10.1136/gutjnl-2018-316407. Epub 2019 May 17.
Results Reference
derived
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Evaluation of Bevacizumab in Combination With First-Line Chemotherapy in Patients Aged 75 Years of Older With Metastatic Colorectal Adenocarcinoma (Prodige20)
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