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

• ClinicalTrials.gov Identifier: NCT00448136
• Recruitment Status: Completed
• First Posted: March 16, 2007
• Results First Posted: January 22, 2015
• Last Update Posted: January 22, 2015
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Neoplasms	Drug: bevacizumab [Avastin]; Drug: 5 FU; Drug: Streptozotocin; Drug: Xeloda	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 83 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Study Start Date: July 2007
• Actual Primary Completion Date: November 2011
• Actual Study Completion Date: November 2011

Arms and Interventions

Arm	Intervention/treatment
Experimental: 1	Drug: bevacizumab [Avastin]; 7.5mg/kg iv on day 1 every 3 weeks; Drug: 5 FU; 400mg/m2/day iv on days 1-5 every 6 weeks; Drug: Streptozotocin; 500mg/m2/day iv on days 1-5 every 6 weeks
Experimental: 2	Drug: bevacizumab [Avastin]; 7.5mg/kg iv on day 1 every 3 weeks; Drug: Xeloda; 1000mg/m2 po bid on days 1-14 every 3 weeks

Outcome Measures

Primary Outcome Measures :

1. Progression-Free Survival (PFS) - Percentage of Participants With an Event [ Time Frame: Screening, every 3 months during treatment, every 6 months during follow-up to 2 years ]
   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.
2. PFS - Time to Event [ Time Frame: Screening, every 3 months during treatment, every 6 months during follow-up to 2 years ]
   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.
3. PFS - Percentage of Participants Estimated to be Progression Free at 12 and 24 Months [ Time Frame: Screening, every 3 months during treatment, every 6 months during follow-up to 2 years ]
   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.

Secondary Outcome Measures :

1. Percentage of Participants With a Response by Best Overall Response [ Time Frame: Screening, every 3 months during treatment, every 6 months during follow-up to 2 years ]
   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.
2. Duration of Overall Response (OR) - Percentage of Participants With an Event [ Time Frame: Screening, every 3 months during treatment, every 6 months during follow-up to 2 years ]
   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.
3. Duration of OR - Time to Event [ Time Frame: Screening, every 3 months during treatment, every 6 months during follow-up to 2 years ]
   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.
4. Duration of OR - Percentage of Participants With Sustained Response at 12 and 24 Months [ Time Frame: Screening, every 3 months during treatment, every 6 months during follow-up to 2 years ]
   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.
5. Duration of Overall Disease Control (ODC) - Percentage of Participants With an Event [ Time Frame: Screening, every 3 months during treatment, every 6 months during follow-up to 2 years ]
   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.
6. Duration of ODC - Time to Event [ Time Frame: Screening, every 3 months during treatment, every 6 months during follow-up to 2 years ]
   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.
7. Duration of ODC - Percentage of Participants Maintaining Disease Control at 12 and 24 Months [ Time Frame: Screening, every 3 months during treatment, every 6 months during follow-up to 2 years ]
   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.
8. Overall Survival (OS) - Percentage of Participants With an Event [ Time Frame: Screening, Day 1 of every cycle during treatment, every 6 months during follow-up to 2 years ]
   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.
9. OS - Time to Event [ Time Frame: Screening, Day 1 of every cycle during treatment, every 6 months during follow-up to 2 years ]
   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.
10. OS - Percentage of Participants Surviving at 12 and 24 Months [ Time Frame: Screening, Day 1 of every cycle during treatment, every 6 months during follow-up to 2 years ]
    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.
11. Global Health Status as Assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - C30 (EORTC QLQ-C30) [ Time Frame: Screening, every 3 months during treatment ]
    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.
12. Percentage of Participants With Change From Baseline in Global Health Status by EORTC QLQ-C30 Improvement Category [ Time Frame: Screening, every 3 months during treatment ]
    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).
13. EORTC QLQ-C30 Functional and Symptom Scale Scores [ Time Frame: Screening, every 3 months during treatment ]
    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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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).

Contacts and Locations

Locations

France

Angers, France, 49933

Bordeaux, France, 33075

Boulogne Billancourt, France, 92104

Caen, France, 14033

Chambray Les Tours, France, 37171

Clichy, France, 92118

Creteil, France, 94010

Dijon, France, 21079

Lille, France, 59020

Lyon, France, 69437

Marseille, France, 13273

Marseille, France, 13285

Marseille, France, 13385

Montpellier, France, 34298

Nantes, France, 44093

Nice, France, 06189

Paris, France, 75571

Paris, France, 75651

Paris, France, 75908

Paris, France, 75970

Poitiers, France, 86021

Reims, France, 51092

Rouen, France, 76031

Saint Brieuc, France, 22015

Strasbourg, France, 67091

Toulouse, France, 31059

Villejuif, France, 94805

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

More Information

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT00448136
• Other Study ID Numbers: ML20383
• First Posted: March 16, 2007
• Results First Posted: January 22, 2015
• Last Update Posted: January 22, 2015
• Last Verified: January 2015

Additional relevant MeSH terms:

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Endocrine System Diseases; Bevacizumab; Streptozocin; Antineoplastic Agents, Immunological; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Growth Inhibitors; Antibiotics, Antineoplastic