Clinical trial NCT01571284: Safety and Quality of Life Study of Aflibercept in Patients With Metastatic Colorectal Cancer Previously Treated With an Oxaliplatin-Based Regimen
Official title: A Multicenter, Single Arm, Open Label Clinical Trial to Evaluate the Safety and Health-Related Quality of Life of Aflibercept in Patients With Metastatic Colorectal Cancer (mCRC) Previously Treated With an Oxaliplatin-Containing Regimen
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Colorectal Cancer Metastatic
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2012-04-05
Enrollment: 781
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Primary Objective:

To provide metastatic colorectal cancer participants with access to aflibercept and to document the overall safety in these participants

Secondary Objective:

To document the Health-Related Quality of Life of aflibercept in this participants population

Detailed description: Each participants will be treated until disease progression, unacceptable toxicity, death, Investigator's decision or participant's refusal for further treatment (whichever comes first). Participants were followed-up during study treatment and for at least 30 days after last administration.

Eligibility criteria: Inclusion criteria :

* Histologically or cytologically proven adenocarcinoma of the colon or rectum.
* Metastatic disease.
* Eastern Cooperative Oncology Group performance status 0-1.
* One and only one prior chemotherapeutic regimen for metastatic disease. This prior chemotherapy was an oxaliplatin containing regimen. Participants must had progressed during or after the oxaliplatin based chemotherapy. Participants relapsed within 6 months of completion of oxaliplatin adjuvant chemotherapy were eligible.
* Signed written informed consent obtained prior to inclusion.

Exclusion criteria:

* Prior therapy with irinotecan.
* Inadequate bone marrow, liver and renal function: neutrophils \< 1.5x109/L, platelets \< 100x109/L, hemoglobin \< 9.0 g/dL, total bilirubin \>1.5 x upper normal limit (ULN), transaminases \>3 x ULN (unless liver metastasis are present), alkaline phosphatase \>3 x ULN (unless liver metastasis are present), serum creatinine \> 1.5 x ULN.
* Less than 4 weeks from prior radiotherapy, prior chemotherapy, prior major surgery (or until the surgical wound were fully healed).
* Treatment with any investigational drug within the prior 30 days.
* Treatment with concomitant anticonvulsivant agents that were CYP3A4 inducers (phenytoin, phenobarbital, carbamazepine), unless discontinued \>7 days.
* History of brain metastases, uncontrolled spinal cord compression, or carcinomatous meningitis or new evidence of brain or leptomeningeal disease.
* Prior malignancy (other than colorectal) including prior malignancy from which the participants had been disease free for \< 5 years (except adequately treated basal or squamous cell skin cancer or carcinoma in situ of the cervix).
* Any of the following within 6 months prior to study inclusion: myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, severe congestive heart failure, stroke or transient ischemic attack.
* Any of the following within 3 months prior study inclusion: severe gastrointestinal bleeding/hemorrhage, treatment resistant peptic ulcer disease, erosive oesophagitis or gastritis, infectious or inflammatory bowel disease, diverticulitis, pulmonary embolism or other uncontrolled thromboembolic event.
* Occurrence of deep vein thrombosis within 4 weeks, prior to study inclusion.
* Known acquired immunodeficiency syndrome (AIDS-related illnesses) or known HIV disease requiring antiretroviral treatment.
* Known dihydropyrimidine dehydrogenase deficiency.
* Predisposing colonic or small bowel disorders in which the symptoms were uncontrolled.
* Prior history of chronic enteropathy, inflammatory enteropathy, chronic diarrhea, unresolved bowel obstruction/sub-obstruction, more than hemicolectomy, extensive small intestine resection with chronic diarrhea.
* Known Gilbert's syndrome.
* Unresolved or unstable toxicity from any prior anti cancer therapy at the time of inclusion.
* History of anaphylaxis or known intolerance to atropine sulphate or loperamide or appropriate antiemetics to be administered in conjunction with FOLFIRI (irinotecan, 5-Fluorouracil, leucovorin).
* Severe acute or chronic medical condition, which could impair the ability of the participants to participate to the study.
* Urine protein-creatinine ratio (UPCR) \>1 on morning spot urinalysis or proteinuria \> 500 mg/24-h.
* Uncontrolled hypertension within 3 months prior to study inclusion.
* Participants on anticoagulant therapy with unstable dose of warfarin and/or had an out-of-therapeutic range INR within the 4 weeks prior to study inclusion.
* Evidence of clinically significant bleeding predisposition or underlying coagulopathy, non-healing wound.
* Pregnant or breast-feeding women.
* Participants with reproductive potential who were not agree to use an accepted effective method of contraception.

The above information wass not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Primary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Baseline up to 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure: 214 weeks)
measure: Number of Participants With Abnormal Hematological Parameters
timeFrame: Baseline up to 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure: 214 weeks)
measure: Number of Participants With International Normalized Ratio (INR)
timeFrame: Baseline up to 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure: 214 weeks)
measure: Number of Participants With Abnormal Electrolytes Parameters
timeFrame: Baseline up to 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure: 214 weeks)
measure: Number of Participants With Abnormal Renal and Liver Function Parameters
timeFrame: Baseline up to 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure: 214 weeks)
measure: Creatinine Clearance of Aflibercept Plus FOLFIRI
timeFrame: Baseline up to 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure: 214 weeks)
measure: Number of Participants With Other Abnormal Biochemistry Parameters
timeFrame: Baseline up to 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure: 214 weeks)
measure: Number of Participants With Abnormal Non-Gradable Biochemistry Parameters
timeFrame: Baseline up to 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure: 214 weeks)
measure: Number of Participants With Proteinuria Events
timeFrame: Baseline up to 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure: 214 weeks)
measure: Number of Participants With Proteinuria Grade >=2
timeFrame: Baseline up to 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure: 214 weeks)
measure: Number of Participants With Urinary Protein-Creatinine Ratio (UPCR)
timeFrame: Baseline up to 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure: 214 weeks)
measure: Number of Participants With Proteinuria (Grade>=2) Concomitant With Hematuria and /or Hypertension
timeFrame: Baseline up to 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure: 214 weeks)
measure: Number of Participants With Cycle Delay and/or Dose Modification
timeFrame: Baseline up to 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure: 214 weeks)
Secondary outcomes:
measure: Mean Change From Baseline in Health Related Quality of Life (HRQL) European Organization for Research and Treatment for Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30 Score): Global Health Status
timeFrame: Pre-dose at Baseline, Day 1 of every odd cycle (from Cycle 3 to 35); at the end of treatment (EOT) (within 30 days of last treatment) (maximum exposure: 214 weeks)
measure: Mean Change From Baseline in HRQL EORTC QLQ-C30 Score: Functional Scales
timeFrame: Pre-dose at Baseline, Day 1 of every odd cycle (from Cycle 3 to 35); at EOT (within 30 days of last treatment) (maximum exposure: 214 weeks)
measure: Change From Baseline in HRQL EORTC QLQ-C30 Score: Symptom Scales
timeFrame: Pre-dose at Baseline, Day 1 of every odd cycle (from Cycle 3 to 35); at EOT (within 30 days of last treatment) (maximum exposure: 214 weeks)
measure: Change From Baseline in HRQL EQ-5D-3L Quality of Life: Single Index Utility Score
timeFrame: Pre-dose at Baseline, Day 1 of every odd cycle (from Cycle 3 to 35); at EOT (within 30 days of last treatment) (maximum exposure: 214 weeks)
measure: Change From Baseline in HRQL EQ-5D-3L VAS Score
timeFrame: Pre-dose at Baseline, Day 1 of every odd cycle (from Cycle 3 to 35); at EOT (within 30 days of last treatment) (maximum exposure: 214 weeks)
Other outcomes:
Locations:
city: Muscle Shoals
country: United States
facility: Investigational Site Number 840-002
state: Alabama
city: Corona
country: United States
facility: Investigational Site Number 840-008
state: California
city: Fountain Valley
country: United States
facility: Investigational Site Number 840-007
state: California
city: Riverside
country: United States
facility: Investigational Site Number 840-004
state: California
city: Indianapolis
country: United States
facility: Investigational Site Number 840-006
state: Indiana
city: Metairie
country: United States
facility: Investigational Site Number 840-011
state: Louisiana
city: Rockville
country: United States
facility: Investigational Site Number 840-001
state: Maryland
city: Howell
country: United States
facility: Investigational Site Number 840-010
state: New Jersey
city: Albuquerque
country: United States
facility: Investigational Site Number 840-012
state: New Mexico
city: Farmington
country: United States
facility: Investigational Site Number 840-009
state: New Mexico
city: Lake Success
country: United States
facility: Investigational Site Number 840-003
state: New York
city: Middletown
country: United States
facility: Investigational Site Number 840-005
state: Ohio
city: Aalst
country: Belgium
facility: Investigational Site Number 056010
city: Arlon
country: Belgium
facility: Investigational Site Number 056015
city: Bonheiden
country: Belgium
facility: Investigational Site Number 056004
city: Edegem
country: Belgium
facility: Investigational Site Number 056001
city: Gent
country: Belgium
facility: Investigational Site Number 056012
city: Haine-Saint-Paul
country: Belgium
facility: Investigational Site Number 056009
city: Liège
country: Belgium
facility: Investigational Site Number 056003
city: Liège
country: Belgium
facility: Investigational Site Number 056007
city: Loverval
country: Belgium
facility: Investigational Site Number 056014
city: Turnhout
country: Belgium
facility: Investigational Site Number 056013
city: Verviers
country: Belgium
facility: Investigational Site Number 056002
city: Yvoir
country: Belgium
facility: Investigational Site Number 056011
city: Brasília
country: Brazil
facility: Investigational Site Number 008
city: Curitiba
country: Brazil
facility: Investigational Site Number 009
city: Fortaleza
country: Brazil
facility: Investigational Site Number 012
city: Passo Fundo
country: Brazil
facility: Investigational Site Number 006
city: Porto Alegre
country: Brazil
facility: Investigational Site Number 003
city: Rio de Janeiro
country: Brazil
facility: Investigational Site Number 002
city: Salvador
country: Brazil
facility: Investigational Site Number 011
city: Sao Jose do Rio Preto
country: Brazil
facility: Investigational Site Number 013
city: São Paulo
country: Brazil
facility: Investigational Site Number 001
city: São Paulo
country: Brazil
facility: Investigational Site Number 004
city: São Paulo
country: Brazil
facility: Investigational Site Number 005
city: Calgary
country: Canada
facility: Investigational Site Number 124002
city: Montreal
country: Canada
facility: Investigational Site Number 124003
city: Montreal
country: Canada
facility: Investigational Site Number 124005
city: Ottawa
country: Canada
facility: Investigational Site Number 124004
city: Québec
country: Canada
facility: Investigational Site Number 124006
city: Toronto
country: Canada
facility: Investigational Site Number 124001
city: Santiago
country: Chile
facility: Investigational Site Number 152001
city: Santiago
country: Chile
facility: Investigational Site Number 152003
city: Brno
country: Czechia
facility: Investigational Site Number 203005
city: Olomouc
country: Czechia
facility: Investigational Site Number 203003
city: Ostrava
country: Czechia
facility: Investigational Site Number 203001
city: Praha 2
country: Czechia
facility: Investigational Site Number 203002
city: Praha 5
country: Czechia
facility: Investigational Site Number 203004
city: Zlin
country: Czechia
facility: Investigational Site Number 203006
city: Cph Ø
country: Denmark
facility: Investigational Site Number 208001
city: Hillerød
country: Denmark
facility: Investigational Site Number 208003
city: Odense C
country: Denmark
facility: Investigational Site Number 208002
city: Oulu
country: Finland
facility: Investigational Site Number 246001
city: Turku
country: Finland
facility: Investigational Site Number 246002
city: Aschaffenburg
country: Germany
facility: Investigational Site Number 276-016
city: Augsburg
country: Germany
facility: Investigational Site Number 276-010
city: Berlin
country: Germany
facility: Investigational Site Number 276-011
city: Erlangen
country: Germany
facility: Investigational Site Number 276-012
city: Frankfurt am Main
country: Germany
facility: Investigational Site Number 276-009
city: Frankfurt am Main
country: Germany
facility: Investigational Site Number 276-013
city: Halle
country: Germany
facility: Investigational Site Number 276-004
city: Krefeld
country: Germany
facility: Investigational Site Number 276-007
city: Lebach
country: Germany
facility: Investigational Site Number 276-003
city: Leipzig
country: Germany
facility: Investigational Site Number 276-019
city: Ludwigsburg
country: Germany
facility: Investigational Site Number 276-008
city: Magdeburg
country: Germany
facility: Investigational Site Number 276-018
city: Magdeburg
country: Germany
facility: Investigational Site Number 276-014
city: Moers
country: Germany
facility: Investigational Site Number 276-006
city: München
country: Germany
facility: Investigational Site Number 276-001
city: München
country: Germany
facility: Investigational Site Number 276-002
city: Northeim
country: Germany
facility: Investigational Site Number 276-015
city: Velbert
country: Germany
facility: Investigational Site Number 276-017
city: Weiden/Oberpfalz
country: Germany
facility: Investigational Site Number 276-005
city: Wolfsburg
country: Germany
facility: Investigational Site Number 276-020
city: Dublin 24
country: Ireland
facility: Investigational Site Number 372002
city: Galway
country: Ireland
facility: Investigational Site Number 372004
city: Wilton
country: Ireland
facility: Investigational Site Number 372001
city: Haifa
country: Israel
facility: Investigational Site Number 376002
city: Jerusalem
country: Israel
facility: Investigational Site Number 376001
city: Petach Tikva
country: Israel
facility: Investigational Site Number 376005
city: Tel Aviv
country: Israel
facility: Investigational Site Number 376003
city: Tel Hashomer
country: Israel
facility: Investigational Site Number 376004
city: Ancona
country: Italy
facility: Investigational Site Number 380-005
city: Bergamo
country: Italy
facility: Investigational Site Number 380-029
city: Bologna
country: Italy
facility: Investigational Site Number 380-021
city: Brescia
country: Italy
facility: Investigational Site Number 380-004
city: Candiolo
country: Italy
facility: Investigational Site Number 380-007
city: Catania
country: Italy
facility: Investigational Site Number 380-012
city: Catanzaro
country: Italy
facility: Investigational Site Number 380-019
city: Firenze
country: Italy
facility: Investigational Site Number 380-023
city: Genova
country: Italy
facility: Investigational Site Number 380-001
city: Meldola
country: Italy
facility: Investigational Site Number 380-014
city: Messina
country: Italy
facility: Investigational Site Number 380-016
city: Milano
country: Italy
facility: Investigational Site Number 380-013
city: Milano
country: Italy
facility: Investigational Site Number 380-015
city: Milano
country: Italy
facility: Investigational Site Number 380-025
city: Napoli
country: Italy
facility: Investigational Site Number 380-022
city: Novara
country: Italy
facility: Investigational Site Number 380-028
city: Padova
country: Italy
facility: Investigational Site Number 380-017
city: Pisa
country: Italy
facility: Investigational Site Number 380-002
city: Reggio Emilia
country: Italy
facility: Investigational Site Number 380-008
city: Roma
country: Italy
facility: Investigational Site Number 380-024
city: Roma
country: Italy
facility: Investigational Site Number 380-010
city: Roma
country: Italy
facility: Investigational Site Number 380-011
city: San Giovanni Rotondo
country: Italy
facility: Investigational Site Number 380-006
city: Sassari
country: Italy
facility: Investigational Site Number 380-026
city: Terni
country: Italy
facility: Investigational Site Number 380-020
city: Torino
country: Italy
facility: Investigational Site Number 380-009
city: Udine
country: Italy
facility: Investigational Site Number 380-003
city: Verona
country: Italy
facility: Investigational Site Number 380-018
city: Beirut
country: Lebanon
facility: Investigational Site Number 1
city: Mexico DF
country: Mexico
facility: Investigational Site Number 484002
city: Mexico DF
country: Mexico
facility: Investigational Site Number 484009
city: Monterrey
country: Mexico
facility: Investigational Site Number 484001
city: México, D.F.
country: Mexico
facility: Investigational Site Number 484010
city: Hoofddorp
country: Netherlands
facility: Investigational Site Number 528001
city: Zwolle
country: Netherlands
facility: Investigational Site Number 528002
city: Bergen
country: Norway
facility: Investigational Site Number 578002
city: Oslo
country: Norway
facility: Investigational Site Number 578001
city: Rio Peidras
country: Puerto Rico
facility: Investigational Site Number 630-001
city: Kazan
country: Russian Federation
facility: Investigational Site Number 643003
city: Moscow
country: Russian Federation
facility: Investigational Site Number 643001
city: Moscow
country: Russian Federation
facility: Investigational Site Number 643004
city: Moscow
country: Russian Federation
facility: Investigational Site Number 643005
city: Moscow
country: Russian Federation
facility: Investigational Site Number 643002
city: Moscow
country: Russian Federation
facility: Investigational Site Number 643006
city: Saint-Petersburg
country: Russian Federation
facility: Investigational Site Number 643009
city: Alicante
country: Spain
facility: Investigational Site Number 724016
city: Barakaldo
country: Spain
facility: Investigational Site Number 724008
city: Cáceres
country: Spain
facility: Investigational Site Number 724012
city: Córdoba
country: Spain
facility: Investigational Site Number 724002
city: Donostia
country: Spain
facility: Investigational Site Number 724013
city: L'Hospitalet de Llobregat
country: Spain
facility: Investigational Site Number 724014
city: Madrid
country: Spain
facility: Investigational Site Number 724003
city: Madrid
country: Spain
facility: Investigational Site Number 724015
city: Madrid
country: Spain
facility: Investigational Site Number 724005
city: Málaga
country: Spain
facility: Investigational Site Number 724004
city: Sabadell
country: Spain
facility: Investigational Site Number 724010
city: Santander
country: Spain
facility: Investigational Site Number 724011
city: Santiago de Compostela
country: Spain
facility: Investigational Site Number 724006
city: Valencia
country: Spain
facility: Investigational Site Number 724001
city: Valencia
country: Spain
facility: Investigational Site Number 724009
city: Zaragoza
country: Spain
facility: Investigational Site Number 724007
city: Jönköping
country: Sweden
facility: Investigational Site Number 752_002
city: Växjö
country: Sweden
facility: Investigational Site Number 752_001
city: Bangkok,TH
country: Thailand
facility: Investigational Site Number 764005
city: Bangkok
country: Thailand
facility: Investigational Site Number 764002
city: Bangkok
country: Thailand
facility: Investigational Site Number 764003
city: Bangkok
country: Thailand
facility: Investigational Site Number 764008
city: Bangkok
country: Thailand
facility: Investigational Site Number 764001
city: Bangkok
country: Thailand
facility: Investigational Site Number 764006
city: Chiang Mai
country: Thailand
facility: Investigational Site Number 764009
city: Khon Kaen
country: Thailand
facility: Investigational Site Number 764004
city: Laksi
country: Thailand
facility: Investigational Site Number 764010
city: Lopburi
country: Thailand
facility: Investigational Site Number 764007
city: Adana
country: Turkey
facility: Investigational Site Number 792-06
city: Ankara
country: Turkey
facility: Investigational Site Number 792-01
city: Ankara
country: Turkey
facility: Investigational Site Number 792-09
city: Ankara
country: Turkey
facility: Investigational Site Number 792-08
city: Capa
country: Turkey
facility: Investigational Site Number 792-02
city: Edirne
country: Turkey
facility: Investigational Site Number 792010
city: Gaziantep
country: Turkey
facility: Investigational Site Number 792-05
city: Istanbul
country: Turkey
facility: Investigational Site Number 792012
city: Istanbul
country: Turkey
facility: Investigational Site Number 792-03
city: Istanbul
country: Turkey
facility: Investigational Site Number 792-04
city: Izmir
country: Turkey
facility: Investigational Site Number 792-007
city: Izmir
country: Turkey
facility: Investigational Site Number 792011
city: Dudley
country: United Kingdom
facility: Investigational Site Number 826005
city: Hull
country: United Kingdom
facility: Investigational Site Number 826011
city: Leicester
country: United Kingdom
facility: Investigational Site Number 826008
city: London
country: United Kingdom
facility: Investigational Site Number 826007
city: London
country: United Kingdom
facility: Investigational Site Number 826012
city: Maidstone,
country: United Kingdom
facility: Investigational Site Number 826003
city: Manchester
country: United Kingdom
facility: Investigational Site Number 826009
city: Newcastle upon tyne
country: United Kingdom
facility: Investigational Site Number 826004
city: Northwood
country: United Kingdom
facility: Investigational Site Number 826006
city: Southampton
country: United Kingdom
facility: Investigational Site Number 826002
city: Sutton
country: United Kingdom
facility: Investigational Site Number 826001
city: Taunton
country: United Kingdom
facility: Investigational Site Number 826010
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: Riechelmann RP, Srimuninnimit V, Bordonaro R, Kavan P, Di Bartolomeo M, Maiello E, Cicin I, Garcia-Alfonso P, Chau I, Fedyanin MY, Martos CF, Ter-Ovanesov M, Peeters M, Ko YJ, Yalcin S, Karthaus M, Aparicio J, Heinemann V, Picard P, Bury D, Drea E, Sobrero A. Aflibercept Plus FOLFIRI for Second-line Treatment of Metastatic Colorectal Cancer: Observations from the Global Aflibercept Safety and Health-Related Quality-of-Life Program (ASQoP). Clin Colorectal Cancer. 2019 Sep;18(3):183-191.e3. doi: 10.1016/j.clcc.2019.05.003. Epub 2019 May 15.