This 2 arm study will assess the efficacy and safety of two systemic treatments including Avastin in patients with previously-untreated progressive locally advanced/metastatic well-differentiated digestive endocrine tumors. Patients with duodeno-pancreatic tumors (arm 1) will be treated with 5FU/streptozotocin iv (5FU 400mg/m2/d D1 to D5;streptozotocin 500mg/m2/d/iv D1 to D5;D1=D42) every 6 weeks, plus Avastin 7.5mg/kg iv every 3 weeks. Patients with gastrointestinal tract tumors (arm 2) will be treated with Xeloda 1000mg/m2 po bid D1 to D14 plus Avastin 7.5mg/kg iv D1=D21 every 3 weeks. The patients will be treated with chemotherapy for a minimum of 6 months, unless there is tumor progression and/or unacceptable toxicity. The anticipated time on study treatment is until disease progression or unacceptable toxicity, and the target sample size is \<100 individuals.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
83
7.5mg/kg iv on day 1 every 3 weeks
400mg/m2/day iv on days 1-5 every 6 weeks
500mg/m2/day iv on days 1-5 every 6 weeks
1000mg/m2 po bid on days 1-14 every 3 weeks
Unnamed facility
Angers, France
Unnamed facility
Bordeaux, France
Unnamed facility
Boulogne-Billancourt, France
Unnamed facility
Caen, France
Unnamed facility
Chambray-lès-Tours, France
Unnamed facility
Clichy, France
Unnamed facility
Créteil, France
Unnamed facility
Dijon, France
Unnamed facility
Lille, France
Unnamed facility
Lyon, France
...and 17 more locations
Progression-Free Survival (PFS) - Percentage of Participants With an Event
PFS is defined as the interval between the date of start of treatment and the date of evaluation by the investigator of progressive disease or death from any cause. The progression was assessed according to Response Evaluation Criteria In Solid Tumors (RECIST) using medical imaging during the treatment period and by the investigators (confirmed by medical imaging) during the follow-up period. Data for participants who were lost to follow-up were censored at the date of last evaluation without progression. Data for participants who completed the study without an event of disease progression or death were censored at the date of the last visit or follow-up without progression.
Time frame: Screening, every 3 months during treatment, every 6 months during follow-up to 2 years
PFS - Time to Event
PFS is defined as the interval between the date of start of treatment and the date of evaluation by the investigator of progressive disease or death from any cause. The progression was assessed according to RECIST using medical imaging during the treatment period and by the investigators (confirmed by medical imaging) during the follow-up period. Data for participants who were lost to follow-up were censored at the date of last evaluation without progression. Data for participants who completed the study without an event of disease progression or death were censored at the date of the last visit or follow-up without progression. Median PFS was estimated using the Kaplan-Meier method.
Time frame: Screening, every 3 months during treatment, every 6 months during follow-up to 2 years
PFS - Percentage of Participants Estimated to be Progression Free at 12 and 24 Months
PFS is defined as the interval between the date of start of treatment and the date of evaluation by the investigator of progressive disease or death from any cause. The progression was assessed according to RECIST using medical imaging during the treatment period and by the investigators (confirmed by medical imaging) during the follow-up period. Data for participants who were lost to follow-up were censored at the date of last evaluation without progression. Data for participants who completed the study without an event of disease progression or death were censored at the date of the last visit or follow-up without progression.
Time frame: Screening, every 3 months during treatment, every 6 months during follow-up to 2 years
Percentage of Participants With a Response by Best Overall Response
Best overall response defined as best response recorded during the study as defined according to RECIST; performed by the investigator and by centralized review. Complete response (CR): complete disappearance of all target lesions and non-target disease. All lesions, both target and non-target, must have decreased to normal (short axis, less than \[\<\]10 millimeters \[mm\]). No new lesions. Partial response (PR): greater than or equal to (≥)30 percent (%) decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter (LD) was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. Stable disease (SD): not qualifying for CR, PR, or Progressive Disease (PD). PD: at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions.
Time frame: Screening, every 3 months during treatment, every 6 months during follow-up to 2 years
Duration of Overall Response (OR) - Percentage of Participants With an Event
Determined only for those participants with an overall response (CR or PR) and was defined as the time interval between the response (CR or PR) and the date of progression or death from any cause. Data for participants who were lost to follow-up were censored at the date of last evaluation without progression. Data for participants who completed the study without an event of progression or death were censored at the data of last visit or follow-up without progression.
Time frame: Screening, every 3 months during treatment, every 6 months during follow-up to 2 years
Duration of OR - Time to Event
Determined only for those participants with an overall response (CR or PR) and was defined as the time interval between the response (CR or PR) and the date of progression or death from any cause. Data for participants who were lost to follow-up were censored at the date of last evaluation without progression. Data for participants who completed the study without an event of progression or death were censored at the data of last visit or follow-up without progression. Median duration of OR was estimated using the Kaplan-Meier method.
Time frame: Screening, every 3 months during treatment, every 6 months during follow-up to 2 years
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Duration of OR - Percentage of Participants With Sustained Response at 12 and 24 Months
Duration of OR was determined only for those participants with an overall response of CR or PR and was defined as the time interval between the response (CR or PR) and the date of progression or death from any cause. Data for participants who were lost to follow-up were censored at the date of last evaluation without progression. Data for participants who completed the study without an event of progression or death were censored at the data of last visit or follow-up without progression.
Time frame: Screening, every 3 months during treatment, every 6 months during follow-up to 2 years
Duration of Overall Disease Control (ODC) - Percentage of Participants With an Event
Determined only for those participants with overall disease control (CR, PR or SD per RECIST) and was defined as the time interval between the first occurrence of disease control (CR, PR or SD) and the date of progression or death from any cause. Data for participants who were lost to follow-up were censored at the date of last evaluation without progression. Data for participants who completed the study without an event of progression or death were censored at the data of last visit or follow-up without progression.
Time frame: Screening, every 3 months during treatment, every 6 months during follow-up to 2 years
Duration of ODC - Time to Event
Determined only for those participants with overall control disease (CR, PR, or SD per RECIST) and was defined as the time interval between the first occurrence of disease control (CR, PR or SD) and the date of progression or death from any cause. Data for participants who were lost to follow-up were censored at the date of last evaluation without progression. Data for participants who completed the study without an event of progression or death were censored at the data of last visit or follow-up without progression. Median time to event was estimated using the Kaplan-Meier method.
Time frame: Screening, every 3 months during treatment, every 6 months during follow-up to 2 years
Duration of ODC - Percentage of Participants Maintaining Disease Control at 12 and 24 Months
Duration of ODC was determined only for those participants with overall control disease (CR, PR, or SD per RECIST) and was defined as the time interval between the first occurrence of disease control (CR, PR, or SD) and the date of progression or death from any cause. Data for participants who were lost to follow-up were censored at the date of last evaluation without progression. Data for participants who completed the study without an event of progression or death were censored at the data of last visit or follow-up without progression.
Time frame: Screening, every 3 months during treatment, every 6 months during follow-up to 2 years
Overall Survival (OS) - Percentage of Participants With an Event
OS was defined as the time from the first treatment administration to death from any cause. Data for participants who were lost to follow-up were censored at the date of last evaluation. Data for participants who were alive at the end of the study were censored at the date of last visit.
Time frame: Screening, Day 1 of every cycle during treatment, every 6 months during follow-up to 2 years
OS - Time to Event
OS was defined as the time from the first treatment administration to death from any cause. Data for participants who were lost to follow-up were censored at the date of last evaluation. Data for participants who were alive at the end of the study were censored at the date of last visit. Median OS was estimated using the Kaplan-Meier method.
Time frame: Screening, Day 1 of every cycle during treatment, every 6 months during follow-up to 2 years
OS - Percentage of Participants Surviving at 12 and 24 Months
OS was defined as the time from the first treatment administration to death from any cause. Data for participants who were lost to follow-up were censored at the date of last evaluation. Data for participants who were alive at the end of the study were censored at the date of last visit.
Time frame: Screening, Day 1 of every cycle during treatment, every 6 months during follow-up to 2 years
Global Health Status as Assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - C30 (EORTC QLQ-C30)
EORTC QLQ-C30: included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting) and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). Most questions used 4-point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale \[1 'very poor' to 7 'Excellent'\]). Scores were averaged and transformed to 0-100 scale; higher score=better level of functioning or greater degree of symptoms.
Time frame: Screening, every 3 months during treatment
Percentage of Participants With Change From Baseline in Global Health Status by EORTC QLQ-C30 Improvement Category
EORTC QLQ-C30: included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting) and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). Most questions used 4-point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale \[1 'very poor' to 7 'Excellent'\]). Scores averaged, transformed to 0-100 scale; higher score=better level of functioning or greater degree of symptoms. Changes from baseline were categorized as follows: Very much worsening (less than \[\<\]-20); Moderate worsening (greater than or equal to \[≥\]-20 to \<-10); Little worsening (≥-10 to \<-5); No change (≥-5 to less than or equal to \[≤\]5); Little improvement (\>5 to ≤10); Moderate improvement (\>10 to ≤20); and Very much improved (\>20).
Time frame: Screening, every 3 months during treatment
EORTC QLQ-C30 Functional and Symptom Scale Scores
EORTC QLQ-C30: included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting) and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). Most questions used 4-point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale \[1 'very poor' to 7 'Excellent'\]). Scores averaged, transformed to 0-100 scale; for functional scores, a higher score represents a better level of functioning. For symptom scale scores a higher level represents a more severe level of symptoms.
Time frame: Screening, every 3 months during treatment