Symptoms and General Pathology

All Conditions

Neoplasms

Gland and Hormone Related Diseases

Disease Progression

Endocrine Gland Neoplasms

Endocrine System Diseases

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Bevacizumab

Fluorouracil

Streptozocin

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Anti-Bacterial Agents

Antibiotics, Antitubercular

bevacizumab [Avastin]

400mg/m2/day iv on days 1-5 every 6 weeks

5 FU

500mg/m2/day iv on days 1-5 every 6 weeks

Streptozotocin

1000mg/m2 po bid on days 1-14 every 3 weeks

Xeloda

Clinical Trials

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.

A Study of Avastin (Bevacizumab) in Combination With Chemotherapy in Patients With Endocrine Tumors of the Gastrointestinal Tract.

An Open Label Study to Evaluate the Effect of Avastin in Association With Chemotherapy on Progression-free Survival in Patients With Progressive Advanced/Metastatic Well-differentiated Digestive Endocrine Tumors of the Gastrointestinal Tract

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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).

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.

Hoffmann-La Roche

All participants who received at least 1 dose of study treatment were included in the safety population. A separate analysis of nonserious AEs was not performed, therefore the AEs presented in the other nonserious AE table include all AEs reported during the study, not just nonserious events.

Cycles 1-5 (42-day cycles): Participants received bevacizumab 7.5 mg/kg IV on Days 1 and 22; 5-FU 400 mg/m\^2/day IV on Days 1 through 5; and streptozocin 500 mg/m\^2/day IV on Days 1 through 5. Days 5-21 and 23-42 were rest periods. This 42-day cycle was repeated at least 4 times.

Bevacizumab + 5-FU + Streptozocin

Cycles 1-9 (21-Day cycle): Participants received bevacizumab 7.5 mg/kg IV on Day 1; capecitabine 2000 mg/m\^2 tablets PO in a divided dose every 12 hours within 30 minutes following a meal, on Days 1 through 14. Days 15-21 were a rest period. This 21-day cycle was repeated at least 8 times.

Bevacizumab + Capecitabine

Cycles 1-9 (21-day cycles): Participants received bevacizumab 7.5 mg/kg IV on Day 1; capecitabine 1000 mg/m\^2, tablets, PO, BID on Days 1 through 14. Days 15-21 were a rest period. This 21-day cycle was repeated at least 8 times.

Total

Age, Continuous

Sex: Female, Male

Intent-to-treat (ITT) population: all participants who received at least 1 dose of treatment.

Medical Communications

Progression-Free Survival (PFS) - Percentage of Participants With an Event

PR (Investigator)

PR (Centralized review)

SD (Investigator)

SD (Centralized review)

PD (Investigator)

PD (Centralized review)

Not evaluable (Investigator)

Not evaluable (Centralized review)

ITT population. Data were missing from centralized review for 1 participant.

Percentage of Participants With a Response by Best Overall Response

ITT population; only participants with a response of CR or PR were included in the analysis.

Duration of Overall Response (OR) - Percentage of Participants With an Event

PFS - Time to Event

12 months

24 months

PFS - Percentage of Participants Estimated to be Progression Free at 12 and 24 Months

Duration of OR - Time to Event

Duration of OR - Percentage of Participants With Sustained Response at 12 and 24 Months

Duration of Overall Disease Control (ODC) - Percentage of Participants With an Event

ITT population; only participants with a response (CR, PR, or SD) were included in the analysis.

Duration of ODC - Time to Event

Duration of ODC - Percentage of Participants Maintaining Disease Control at 12 and 24 Months

Overall Survival (OS) - Percentage of Participants With an Event

OS - Time to Event

OS - Percentage of Participants Surviving at 12 and 24 Months

Baseline (n=29,40)

3 months (n=20,32)

6 months (n=20,24)

12 months (n=13,14)

End of treatment (n=13,23)

ITT population; only participants who completed the questionnaire at baseline and who had at least 1 post-baseline assessment were included in the analysis. Number (n) equals (=) the number of participants assessed for the specified parameter at a given visit.

Global Health Status as Assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - C30 (EORTC QLQ-C30)

3 months, Very much worsening (n=20,29)

3 months, Moderate worsening (n=20,29)

3 months, Little worsening (n=20,29)

3 months, No change (n=20,29)

3 months, Little improving (n=20,29)

3 months, Moderate Improving (n=20,29)

3 months, Very much improving (n=20,29)

6 months, Very much worsening (n=20,22)

6 months, Moderate worsening (n=20,22)

6 months, Little worsening (n=20,22)

6 months, No change (n=20,22)

6 months, Little improving (n=20,22)

6 months, Moderate Improving (n=20,22)

6 months, Very much improving (n=20,22)

12 months, Very much worsening (n=12,13)

12 months, Moderate worsening (n=12,13)

12 months - Little worsening (n=12,13)

12 months, No change (n=12,13)

12 months, Little improving (n=12,13)

12 months, Moderate Improving (n=12,13)

12 months, Very much improving (n=12,13)

End of treatment, Very much worsening (n=13,20)

End of treatment, Moderate worsening (n=13,20)

End of treatment, Little worsening (n=13,20)

End of treatment, No change (n=13,20)

End of treatment, Little improving (n=13,20)

End of treatment, Moderate Improving (n=13,20)

End of treatment, Very much improving (n=13,20)

ITT population; only participants who completed the questionnaire at baseline and who had at least 1 post-baseline assessment were included in the analysis. n=number of participants assessed for the specified parameter at a given visit.

Percentage of Participants With Change From Baseline in Global Health Status by EORTC QLQ-C30 Improvement Category

Physical functioning, Baseline (n=30,43)

Physical functioning, 3 months (n=22,33)

Physical functioning, 6 months (n=21,24)

Physical functioning, End of Treatment (n=13,24)

Role functioning, Baseline (n=30,43)

Role functioning, 3 months (n=22,33)

Role functioning, 6 months (n=21,24)

Role functioning, End of Treatment (n=13,24)

Emotional functioning, Baseline (n=30,42)

Emotional functioning, 3 months (n=21,33)

Emotional functioning, 6 months (n=21,24)

Emotional functioning, End of Treatment (n=13,24)

Cognitive functioning, Baseline (n=30,42)

Cognitive functioning, 3 months (n=22,33)

Cognitive functioning, 6 months (n=21,24)

Cognitive functioning, End of Treatment (n=13,24)

Social functioning, Baseline (n=30,41)

Social functioning, 3 months (n=22,33)

Social functioning, 6 months (n=21,24)

Social functioning, End of Treatment (n=13,24)

Fatigue, Baseline (n=30,42)

Fatigue, 3 months (n=21,33)

Fatigue, 6 months (n=20,24)

Fatigue, End of Treatment (n=13,24)

Nausea and vomiting, Baseline (n=30,42)

Nausea and vomiting, 3 months (n=22,33)

Nausea and vomiting, 6 months (n=21,24)

Nausea and vomiting, End of Treatment (n=13,24)

Pain, Baseline (n=30,43)

Pain, 3 months (n=22,33)

Pain, 6 months (n=21,24)

Pain, End of Treatment (n=13,24)

Dyspnea, Baseline (n=30,43)

Dyspnea, 3 months (n=21,33)

Dyspnea, 6 months (n=21,23)

Dyspnea, End of Treatment (n=13,24)

Insomnia, Baseline (n=30,43)

Insomnia, 3 months (n=21,33)

Insomnia, 6 months (n=21,24)

Insomnia, End of Treatment (n=13,24)

Appetite loss, Baseline (n=29,42)

Appetite loss, 3 months (n=22,33)

Appetite loss, 6 months (n=21,24)

Appetite loss, End of Treatment (n=13,24)

Constipation, Baseline (n=27,40)

Constipation, 3 months (n=21,33)

Constipation, 6 months (n=21,23)

Constipation, End of Treatment (n=13,24)

Diarrhea, Baseline (n=30,41)

Diarrhea, 3 months (n=22,32)

Diarrhea, 6 months (n=21,23)

Diarrhea, End of Treatment (n=12,22)

Financial difficulties, Baseline (n=30,413)

Financial difficulties, 3 months (n=22,33)

Financial difficulties, 6 months (n=21,23)

Financial difficulties, End of treatment (n=13,24)

EORTC QLQ-C30 Functional and Symptom Scale Scores

Cycles 1-5 (42-day cycles): Participants received bevacizumab 7.5 milligrams per kilogram (mg/kg) intravenously (IV) on Days 1 and 22; 5-FU 400 mg per square meter per day (mg/m\^2/day) IV on Days 1 through 5; and streptozocin 500 mg/m\^2/day IV on Days 1 through 5. Days 5-21 and 23-42 were rest periods. This 42-day cycle was repeated at least 4 times.

Bevacizumab + 5-fluorouracil (5-FU) + Streptozocin

Cycles 1-9 (21-day cycles): Participants received bevacizumab 7.5 mg/kg IV on Day 1; capecitabine 1000 mg/m\^2, tablets, orally (PO), twice daily (BID) on Days 1 through 14. Days 15-21 were a rest period. This 21-day cycle was repeated at least 8 times.

Overall Study

Spots Global Cancer Trial Database for A Study of Avastin (Bevacizumab) in Combination With Chemotherapy in Patients With Endocrine Tumors of the Gastrointestinal Tract.

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial