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

Neoplasms Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00448136
• Other study ID #: ML20383
• Status: Completed
• Phase: Phase 2
• First received: March 15, 2007
• Last updated: January 20, 2015
• Start date: July 2007
• Est. completion date: November 2011

Study information

• Verified date: January 2015
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: AFSSAPS (Agence francaise de securite sanitaire des produits de sante)
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 83
• Est. completion date: November 2011
• Est. primary completion date: November 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• adult patients, >=18 years of age;

• well-differentiated gastrointestinal tract endocrine tumors, or duodeno-pancreatic endocrine tumors;

• no previous anti-cancer therapy, other than surgery;

• progressive metastatic disease;

• >=1 measurable lesion.

Exclusion Criteria:

• abnormal cardiac function, with history of ischemic heart disease in past 6 months and/or abnormal 12 lead ECG;

• patients with known bleeding disorders;

• unstable systemic disease;

• chronic daily treatment with high-dose aspirin, NSAIDs or corticosteroids;

• previous history of malignancy (other than successfully treated basal and squamous cell cancer of the skin, and/or in situ cancer of the cervix).

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Endocrine Gland Neoplasms
• Neoplasms

Intervention

Drug:
• bevacizumab [Avastin]
7.5mg/kg iv on day 1 every 3 weeks
• 5 FU
400mg/m2/day iv on days 1-5 every 6 weeks
• Streptozotocin
500mg/m2/day iv on days 1-5 every 6 weeks
• Xeloda
1000mg/m2 po bid on days 1-14 every 3 weeks

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Screening, every 3 months during treatment, every 6 months during follow-up to 2 years	No
Primary	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.	Screening, every 3 months during treatment, every 6 months during follow-up to 2 years	No
Primary	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.	Screening, every 3 months during treatment, every 6 months during follow-up to 2 years	No
Secondary	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.	Screening, every 3 months during treatment, every 6 months during follow-up to 2 years	No
Secondary	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.	Screening, every 3 months during treatment, every 6 months during follow-up to 2 years	No
Secondary	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.	Screening, every 3 months during treatment, every 6 months during follow-up to 2 years	No
Secondary	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.	Screening, every 3 months during treatment, every 6 months during follow-up to 2 years	No
Secondary	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.	Screening, every 3 months during treatment, every 6 months during follow-up to 2 years	No
Secondary	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.	Screening, every 3 months during treatment, every 6 months during follow-up to 2 years	No
Secondary	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.	Screening, every 3 months during treatment, every 6 months during follow-up to 2 years	No
Secondary	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.	Screening, Day 1 of every cycle during treatment, every 6 months during follow-up to 2 years	No
Secondary	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.	Screening, Day 1 of every cycle during treatment, every 6 months during follow-up to 2 years	No
Secondary	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.	Screening, Day 1 of every cycle during treatment, every 6 months during follow-up to 2 years	No
Secondary	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.	Screening, every 3 months during treatment	No
Secondary	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).	Screening, every 3 months during treatment	No
Secondary	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.	Screening, every 3 months during treatment	No