Safety and Quality of Life Study of Aflibercept in Patients With Metastatic Colorectal Cancer Previously Treated With an Oxaliplatin-Based Regimen

Colorectal Cancer Metastatic Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01571284
• Other study ID #: AFLIBC06097
• Secondary ID: 2011-005724-17U1
• Status: Completed
• Phase: Phase 3
• First received: April 3, 2012
• Last updated: March 19, 2018
• Start date: May 30, 2012
• Est. completion date: January 31, 2017

Study information

• Verified date: March 2018
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 781
• Est. completion date: January 31, 2017
• Est. primary completion date: January 31, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Colorectal Cancer Metastatic
• Colorectal Neoplasms

Intervention

Drug:
• AFLIBERCEPT AVE0005
Pharmaceutical form:Concentrate for solution for infusion Route of administration: Intravenous
• FOLFIRI
irinotecan, 5-FU and leucovorin

Locations

Country	Name	City	State
Belgium	Investigational Site Number 056010	Aalst
Belgium	Investigational Site Number 056015	Arlon
Belgium	Investigational Site Number 056004	Bonheiden
Belgium	Investigational Site Number 056001	Edegem
Belgium	Investigational Site Number 056012	Gent
Belgium	Investigational Site Number 056009	Haine-Saint-Paul
Belgium	Investigational Site Number 056003	Liège
Belgium	Investigational Site Number 056007	Liège
Belgium	Investigational Site Number 056014	Loverval
Belgium	Investigational Site Number 056013	Turnhout
Belgium	Investigational Site Number 056002	Verviers
Belgium	Investigational Site Number 056011	Yvoir
Brazil	Investigational Site Number 008	Brasília
Brazil	Investigational Site Number 009	Curitiba
Brazil	Investigational Site Number 012	Fortaleza
Brazil	Investigational Site Number 006	Passo Fundo
Brazil	Investigational Site Number 003	Porto Alegre
Brazil	Investigational Site Number 002	Rio de Janeiro
Brazil	Investigational Site Number 011	Salvador
Brazil	Investigational Site Number 013	Sao Jose do Rio Preto
Brazil	Investigational Site Number 001	São Paulo
Brazil	Investigational Site Number 004	São Paulo
Brazil	Investigational Site Number 005	São Paulo
Canada	Investigational Site Number 124002	Calgary
Canada	Investigational Site Number 124003	Montreal
Canada	Investigational Site Number 124005	Montreal
Canada	Investigational Site Number 124004	Ottawa
Canada	Investigational Site Number 124006	Québec
Canada	Investigational Site Number 124001	Toronto
Chile	Investigational Site Number 152001	Santiago
Chile	Investigational Site Number 152003	Santiago
Czechia	Investigational Site Number 203005	Brno
Czechia	Investigational Site Number 203003	Olomouc
Czechia	Investigational Site Number 203001	Ostrava
Czechia	Investigational Site Number 203002	Praha 2
Czechia	Investigational Site Number 203004	Praha 5
Czechia	Investigational Site Number 203006	Zlin
Denmark	Investigational Site Number 208001	Cph Ø
Denmark	Investigational Site Number 208003	Hillerød
Denmark	Investigational Site Number 208002	Odense C
Finland	Investigational Site Number 246001	Oulu
Finland	Investigational Site Number 246002	Turku
Germany	Investigational Site Number 276-016	Aschaffenburg
Germany	Investigational Site Number 276-010	Augsburg
Germany	Investigational Site Number 276-011	Berlin
Germany	Investigational Site Number 276-012	Erlangen
Germany	Investigational Site Number 276-009	Frankfurt am Main
Germany	Investigational Site Number 276-013	Frankfurt am Main
Germany	Investigational Site Number 276-004	Halle
Germany	Investigational Site Number 276-007	Krefeld
Germany	Investigational Site Number 276-003	Lebach
Germany	Investigational Site Number 276-019	Leipzig
Germany	Investigational Site Number 276-008	Ludwigsburg
Germany	Investigational Site Number 276-014	Magdeburg
Germany	Investigational Site Number 276-018	Magdeburg
Germany	Investigational Site Number 276-006	Moers
Germany	Investigational Site Number 276-001	München
Germany	Investigational Site Number 276-002	München
Germany	Investigational Site Number 276-015	Northeim
Germany	Investigational Site Number 276-017	Velbert
Germany	Investigational Site Number 276-005	Weiden/Oberpfalz
Germany	Investigational Site Number 276-020	Wolfsburg
Ireland	Investigational Site Number 372002	Dublin 24
Ireland	Investigational Site Number 372004	Galway
Ireland	Investigational Site Number 372001	Wilton
Israel	Investigational Site Number 376002	Haifa
Israel	Investigational Site Number 376001	Jerusalem
Israel	Investigational Site Number 376005	Petach Tikva
Israel	Investigational Site Number 376003	Tel Aviv
Israel	Investigational Site Number 376004	Tel Hashomer
Italy	Investigational Site Number 380-005	Ancona
Italy	Investigational Site Number 380-029	Bergamo
Italy	Investigational Site Number 380-021	Bologna
Italy	Investigational Site Number 380-004	Brescia
Italy	Investigational Site Number 380-007	Candiolo
Italy	Investigational Site Number 380-012	Catania
Italy	Investigational Site Number 380-019	Catanzaro
Italy	Investigational Site Number 380-023	Firenze
Italy	Investigational Site Number 380-001	Genova
Italy	Investigational Site Number 380-014	Meldola
Italy	Investigational Site Number 380-016	Messina
Italy	Investigational Site Number 380-013	Milano
Italy	Investigational Site Number 380-015	Milano
Italy	Investigational Site Number 380-025	Milano
Italy	Investigational Site Number 380-022	Napoli
Italy	Investigational Site Number 380-028	Novara
Italy	Investigational Site Number 380-017	Padova
Italy	Investigational Site Number 380-002	Pisa
Italy	Investigational Site Number 380-008	Reggio Emilia
Italy	Investigational Site Number 380-010	Roma
Italy	Investigational Site Number 380-011	Roma
Italy	Investigational Site Number 380-024	Roma
Italy	Investigational Site Number 380-006	San Giovanni Rotondo
Italy	Investigational Site Number 380-026	Sassari
Italy	Investigational Site Number 380-020	Terni
Italy	Investigational Site Number 380-009	Torino
Italy	Investigational Site Number 380-003	Udine
Italy	Investigational Site Number 380-018	Verona
Lebanon	Investigational Site Number 1	Beirut
Mexico	Investigational Site Number 484002	Mexico DF
Mexico	Investigational Site Number 484009	Mexico DF
Mexico	Investigational Site Number 484010	México, D.F.
Mexico	Investigational Site Number 484001	Monterrey
Netherlands	Investigational Site Number 528001	Hoofddorp
Netherlands	Investigational Site Number 528002	Zwolle
Norway	Investigational Site Number 578002	Bergen
Norway	Investigational Site Number 578001	Oslo
Puerto Rico	Investigational Site Number 630-001	Rio Peidras
Russian Federation	Investigational Site Number 643003	Kazan
Russian Federation	Investigational Site Number 643001	Moscow
Russian Federation	Investigational Site Number 643002	Moscow
Russian Federation	Investigational Site Number 643004	Moscow
Russian Federation	Investigational Site Number 643005	Moscow
Russian Federation	Investigational Site Number 643006	Moscow
Russian Federation	Investigational Site Number 643009	Saint-Petersburg
Spain	Investigational Site Number 724016	Alicante
Spain	Investigational Site Number 724008	Barakaldo
Spain	Investigational Site Number 724012	Cáceres
Spain	Investigational Site Number 724002	Córdoba
Spain	Investigational Site Number 724013	Donostia
Spain	Investigational Site Number 724014	L'Hospitalet de Llobregat
Spain	Investigational Site Number 724003	Madrid
Spain	Investigational Site Number 724005	Madrid
Spain	Investigational Site Number 724015	Madrid
Spain	Investigational Site Number 724004	Málaga
Spain	Investigational Site Number 724010	Sabadell
Spain	Investigational Site Number 724011	Santander
Spain	Investigational Site Number 724006	Santiago de Compostela
Spain	Investigational Site Number 724001	Valencia
Spain	Investigational Site Number 724009	Valencia
Spain	Investigational Site Number 724007	Zaragoza
Sweden	Investigational Site Number 752_002	Jönköping
Sweden	Investigational Site Number 752_001	Växjö
Thailand	Investigational Site Number 764001	Bangkok
Thailand	Investigational Site Number 764002	Bangkok
Thailand	Investigational Site Number 764003	Bangkok
Thailand	Investigational Site Number 764006	Bangkok
Thailand	Investigational Site Number 764008	Bangkok
Thailand	Investigational Site Number 764005	Bangkok,TH
Thailand	Investigational Site Number 764009	Chiang Mai
Thailand	Investigational Site Number 764004	Khon Kaen
Thailand	Investigational Site Number 764010	Laksi
Thailand	Investigational Site Number 764007	Lopburi
Turkey	Investigational Site Number 792-06	Adana
Turkey	Investigational Site Number 792-01	Ankara
Turkey	Investigational Site Number 792-08	Ankara
Turkey	Investigational Site Number 792-09	Ankara
Turkey	Investigational Site Number 792-02	Capa
Turkey	Investigational Site Number 792010	Edirne
Turkey	Investigational Site Number 792-05	Gaziantep
Turkey	Investigational Site Number 792-03	Istanbul
Turkey	Investigational Site Number 792-04	Istanbul
Turkey	Investigational Site Number 792012	Istanbul
Turkey	Investigational Site Number 792-007	Izmir
Turkey	Investigational Site Number 792011	Izmir
United Kingdom	Investigational Site Number 826005	Dudley
United Kingdom	Investigational Site Number 826011	Hull
United Kingdom	Investigational Site Number 826008	Leicester
United Kingdom	Investigational Site Number 826007	London
United Kingdom	Investigational Site Number 826012	London
United Kingdom	Investigational Site Number 826003	Maidstone,
United Kingdom	Investigational Site Number 826009	Manchester
United Kingdom	Investigational Site Number 826004	Newcastle upon tyne
United Kingdom	Investigational Site Number 826006	Northwood
United Kingdom	Investigational Site Number 826002	Southampton
United Kingdom	Investigational Site Number 826001	Sutton
United Kingdom	Investigational Site Number 826010	Taunton
United States	Investigational Site Number 840-012	Albuquerque	New Mexico
United States	Investigational Site Number 840-008	Corona	California
United States	Investigational Site Number 840-009	Farmington	New Mexico
United States	Investigational Site Number 840-007	Fountain Valley	California
United States	Investigational Site Number 840-010	Howell	New Jersey
United States	Investigational Site Number 840-006	Indianapolis	Indiana
United States	Investigational Site Number 840-003	Lake Success	New York
United States	Investigational Site Number 840-011	Metairie	Louisiana
United States	Investigational Site Number 840-005	Middletown	Ohio
United States	Investigational Site Number 840-002	Muscle Shoals	Alabama
United States	Investigational Site Number 840-004	Riverside	California
United States	Investigational Site Number 840-001	Rockville	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
Sanofi	Regeneron Pharmaceuticals

Countries where clinical trial is conducted

United States,  Belgium,  Brazil,  Canada,  Chile,  Czechia,  Denmark,  Finland,  Germany,  Ireland,  Israel,  Italy,  Lebanon,  Mexico,  Netherlands,  Norway,  Puerto Rico,  Russian Federation,  Spain,  Sweden,  Thailand,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	Any untoward medical occurrence in a participant who received investigational medicinal product (IMP) was considered an adverse event (AE) without regard to possibility of causal relationship with this treatment. A serious AE (SAE): Any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious AEs. National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Version 4.03 was used to assess severity (Grade 1=mild, Grade 2= moderate, Grade 3= severe, Grade 4= life-threatening/disabling) of AEs.	Baseline up to 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure: 214 weeks)
Primary	Number of Participants With Abnormal Hematological Parameters	Abnormal hematological parameters included: anaemia, thrombocytopenia, leukopenia and neutropenia. Number of participants with each of these parameters were analyzed by grades (All Grades and Grades 3-4 as per NCI CTCAE (Version 4.03), where Grade 1=mild, Grade 2= moderate, Grade 3= severe, Grade 4= life-threatening/disabling. All Grades included Grades 1-4.	Baseline up to 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure: 214 weeks)
Primary	Number of Participants With International Normalized Ratio (INR)	The INR is a derived measure of the prothrombin time. The INR is the ratio of a participant's prothrombin time to a normal control sample. Normal range (without anti coagulation therapy): 0.8-1.2; Targeted range (with anti coagulation therapy) 2.0-3.0.	Baseline up to 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure: 214 weeks)
Primary	Number of Participants With Abnormal Electrolytes Parameters	Abnormal electrolytes parameters included: hyponatremia, hypernatremia, hypocalcemia, hypercalcemia, hypokalemia, and hyperkalemia. Number of participants with each of these parameters were analyzed by grades ( All Grades and Grades 3-4 as per NCI CTCAE Version 4.03, where Grade 1=mild, Grade 2= moderate, Grade 3= severe, Grade 4= life-threatening/disabling. All Grades included Grades 1-4.	Baseline up to 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure: 214 weeks)
Primary	Number of Participants With Abnormal Renal and Liver Function Parameters	Renal and liver function parameters included: creatinine, hyperbilirubinemia, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase. Number of participants with each of these parameters were analyzed by grades (All Grades and Grades 3-4) as per NCI CTCAE version 4.03, where Grade 1=mild, Grade 2= moderate, Grade 3= severe, Grade 4= life-threatening/disabling. All Grades included Grades 1-4.	Baseline up to 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure: 214 weeks)
Primary	Creatinine Clearance of Aflibercept Plus FOLFIRI	Creatinine clearance is a measure of kidney function. Creatinine clearance rate is the volume of blood plasma that is cleared of creatinine by the kidneys per unit time. Creatinine clearance can be measured directly or estimated using established formulas. For this study, the creatinine clearance was calculated using the Cockroft-Gault or Modification of Diet in Renal Disease (MDRD).	Baseline up to 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure: 214 weeks)
Primary	Number of Participants With Other Abnormal Biochemistry Parameters	Other abnormal biochemistry parameters included: hypoglycemia, hyperglycemia and hypoalbuminemia. Number of participants with each of these parameters were analyzed by grades (All Grades and Grades 3-4) as per NCI CTCAE Version 4.03, where Grade 1= mild, Grade 2= moderate, Grade 3= severe, Grade 4= life-threatening/disabling. All Grades included Grades 1-4.	Baseline up to 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure: 214 weeks)
Primary	Number of Participants With Abnormal Non-Gradable Biochemistry Parameters	Non-gradeable biochemistry parameters included; chloride, urea, total protein, blood urea nitrogen (BUN) and lactate dehydrogenase (LDH). Number of participants with	Baseline up to 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure: 214 weeks)
Primary	Number of Participants With Proteinuria Events	Proteinuria is defined as the ratio of protein to creatinine. Number of participants with proteinuria were analyzed by grades (Grades 1, 2, 3 ,4) as per NCI CTCAE Version 4.03 where Grade 1= mild, Grade 2= moderate, Grade 3= severe, Grade 4= life-threatening/disabling.	Baseline up to 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure: 214 weeks)
Primary	Number of Participants With Proteinuria Grade >=2	Proteinuria is defined as the ratio of protein to creatinine. Number of participants with proteinuria grade >=2 (graded as per NCI CTCAE Version 4.03), where Grade>=2 represents moderate to life-threatening/disabling event.	Baseline up to 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure: 214 weeks)
Primary	Number of Participants With Urinary Protein-Creatinine Ratio (UPCR)	Urinary protein creatinine ratio (UPCR) corresponds to the ratio of the urinary protein and urinary creatinine concentration (expressed in mg/dL). This ratio provides an accurate quantification of 24-hours urinary protein excretion. There is a high correlation between morning UPCR and 24-hour proteinuria in participants with normal or reduced renal functions. Normal ratio is < or = 1.	Baseline up to 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure: 214 weeks)
Primary	Number of Participants With Proteinuria (Grade>=2) Concomitant With Hematuria and /or Hypertension	Proteinuria is defined as the presence of excess proteins in the urine (assessed either by spot sample, dipstick/ urine protein or 24 hour urine collection). Hematuria is defined as the presence of blood in urine (positive dipstick for RBC or reported AE). Number of participants with proteinuria grade >=2 (graded as per NCI CTCAE Version 4.03), where Grade>=2 represents moderate to life-threatening/disabling event. Hypertension (high blood pressure) is defined as having a blood pressure reading of more than 140/90 mmHg over a number of weeks.	Baseline up to 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure: 214 weeks)
Primary	Number of Participants With Cycle Delay and/or Dose Modification	A theoretical cycle is a 2 week period i.e. 14 days. A cycle is delayed if duration of previous cycle is greater than 14+2 days ; dose modification includes dose reduction and dose omission.	Baseline up to 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure: 214 weeks)
Secondary	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	EORTC-QLQ-C30 is a cancer-specific instrument with 30 questions for evaluation of new chemotherapy and provides an assessment of participant reported outcome dimensions. First 28 questions used 4-point scale (1=not at all,2=a little,3=quite a bit,4=very much) for evaluating 5 functional scales (physical,role,emotional,cognitive,social), 3 symptom scales (fatigue,nausea/vomiting,pain) & other single items. For each item,high score represented high level of symptomatology/problem. Last 2 questions represented participant's assessment of overall health & quality of life, coded on 7-point scale (1=very poor to 7=excellent).EORTC QLQ-C30 observed values and change from baseline for global health status (scoring of questions 29 & 30) and 5 functional scales, 3 symptom scales and other single items (scoring of questions 1 to 28). Answers were converted into grading scale, with values between 0 and 100. A high score represented a favourable outcome with a best quality of life for participant.	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)
Secondary	Mean Change From Baseline in HRQL EORTC QLQ-C30 Score: Functional Scales	EORTC-QLQ-C30 is a cancer-specific instrument with 30 questions for evaluation of new chemotherapy and provides an assessment of participant reported outcome dimensions. First 28 questions used 4-point scale (1=not at all,2=a little,3=quite a bit,4=very much) for evaluating 5 functional scales (physical,role,emotional,cognitive,social), 3 symptom scales (fatigue,nausea/vomiting,pain) & other single items. For each item,high score represented high level of symptomatology/problem. Last 2 questions represented participant's assessment of overall health & quality of life, coded on 7-point scale (1=very poor to 7=excellent). EORTC QLQ-C30 observed values and change from baseline for global health status (scoring of questions 29 & 30) and 5 functional scales, 3 symptom scales and other single items (scoring of questions 1 to 28).Answers were converted into grading scale, with values between 0 and 100. A high score represented a favourable outcome with a best quality of life for participant.	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)
Secondary	Change From Baseline in HRQL EORTC QLQ-C30 Score: Symptom Scales	EORTC-QLQ-C30 is a cancer-specific instrument with 30 questions for evaluation of new chemotherapy and provides an assessment of participant reported outcome dimensions. First 28 questions used 4-point scale (1=not at all,2=a little,3=quite a bit,4=very much) for evaluating 5 functional scales (physical,role,emotional,cognitive,social), 3 symptom scales (fatigue,nausea/vomiting,pain) & other single items. For each item,high score represented high level of symptomatology/problem. Last 2 questions represented participant's assessment of overall health & quality of life, coded on 7-point scale (1=very poor to 7=excellent). EORTC QLQ-C30 observed values and change from baseline for global health status (scoring of questions 29 & 30) and 5 functional scales, 3 symptom scales and other single items (scoring of questions 1 to 28). Answers were converted into grading scale, with values between 0 and 100. A high score represented a favorable outcome with a best quality of life for participant.	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)
Secondary	Change From Baseline in HRQL EQ-5D-3L Quality of Life: Single Index Utility Score	EQ-5D was a standardized HRQL questionnaire consisting of EQ-5D descriptive system and Visual Analogue Scale (VAS). EQ-5D descriptive system comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression measured on 3 levels (no problem, some problems & severe problems) within a particular EQ-5D dimension. 5 dimensional 3-level system was converted into single index utility score. Possible values for single index utility score ranged from -0.594 (severe problems in all dimensions) to 1.0 (no problem in all dimensions) on scale where 1 represented best possible health state.	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)
Secondary	Change From Baseline in HRQL EQ-5D-3L VAS Score	EQ-5D was a standardized HRQL questionnaire consisting of EQ-5D descriptive system and VAS. EQ-5D descriptive system comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression measured on 3 levels (no problem, some problems & severe problems) within a particular EQ-5D dimension. 5 dimensional 3-level system was converted into single index utility score. The VAS recorded the respondent's self-rated health on a vertical visual analogue scale. The VAS 'thermometer' has endpoints of 100 (Best imaginable health state) at the top and 0 (Worst imaginable health state) at the bottom. This information can be used as a quantitative measure of health outcome as judged by the individual respondents.	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)