Trial Outcomes & Findings for Avastin (Bevacizumab) and RAD001 (Everolimus) in Advanced Low or Intermediate Grade Neuroendocrine Carcinoma (NCT NCT00607113)

Last Updated: 2013-07-18

Results Overview

Tumor blood flow (ml/min/100gm) determined by functional computed tomography (CT). Functional computed tomography (CT) at baseline, after first and third cycles (21 day cycles). Change (percentage) calculated as tumor blood flow measured at baseline compared to tumor blood flow measurement taken at end of Cycle 1, week 3 (21 days), and again at end of Cycle 3, Week 9 (63 days).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

41 participants

Primary outcome timeframe

Baseline to end of Cycle 3 (63 days)

Results posted on

2013-07-18

Participant Flow

Participants were recruited starting on January 17, 2008 to February 26, 2010. All recruitment was done at The University of Texas MD Anderson Cancer Center.

A total of forty-one (41) participants were enrolled in the trial but two (2) participants were not eligible due to screen failure, therefore, they were not included in the group assignments.

Participant milestones

Participant milestones
Measure	Avastin Cycle 1: (First 3 weeks of study) - Avastin 15 mg/kg intravenous (IV), Cycle 2: Avastin 15 mg/kg IV every 3 weeks, RAD001 10 mg orally daily for 3 weeks	RAD001 Cycle 1: (First 3 weeks of study) - RAD001 10 mg orally daily for 21 Days, Cycle 2: Avastin 15 mg/kg IV every 3 weeks, RAD001 10 mg orally daily for 3 weeks
Overall Study STARTED	19	20
Overall Study COMPLETED	19	20
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Avastin (Bevacizumab) and RAD001 (Everolimus) in Advanced Low or Intermediate Grade Neuroendocrine Carcinoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Avastin n=19 Participants Cycle 1: (First 3 weeks of study) - Avastin 15 mg/kg intravenous (IV), Cycle 2: Avastin 15 mg/kg IV every 3 weeks, RAD001 10 mg orally daily for 3 weeks	RAD001 n=20 Participants Cycle 1: (First 3 weeks of study) - RAD001 10 mg orally daily for 21 Days, Cycle 2: Avastin 15 mg/kg IV every 3 weeks, RAD001 10 mg orally daily for 3 weeks	Total n=39 Participants Total of all reporting groups
Age Continuous	57 years n=5 Participants	60 years n=7 Participants	59 years n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	12 Participants n=7 Participants	23 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	8 Participants n=7 Participants	16 Participants n=5 Participants
Region of Enrollment United States	19 participants n=5 Participants	20 participants n=7 Participants	39 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to end of Cycle 3 (63 days)

Outcome measures

Outcome measures
Measure	Avastin n=19 Participants Cycle 1 (First 3 weeks of study) - Avastin 15 mg/kg intravenous (IV) or RAD001 10 mg orally daily for 21 Days, Cycle 2: Avastin 15 mg/kg IV every 3 weeks, RAD001 10 mg orally daily for 3 weeks	RAD001 n=20 Participants Cycle 1: (First 3 weeks of study) - RAD001 10 mg orally daily for 21 Days, Cycle 2: Avastin 15 mg/kg IV every 3 weeks, RAD001 10 mg orally daily for 3 weeks
Net Change Relative to Baseline in Tumor Blood Flow Baseline to Week 3	-0.44 ml/min/100gm Standard Deviation 0.32 • Interval 73.2 to 40.98	-0.12 ml/min/100gm Standard Deviation 08.16 • Interval 66.89 to 58.73
Net Change Relative to Baseline in Tumor Blood Flow Baseline to Week 9	-0.60 ml/min/100gm Standard Deviation 0.44 • Interval 73.2 to 29.07	-0.40 ml/min/100gm Standard Deviation 0.27 • Interval 66.89 to 40.15

Adverse Events

Avastin + RAD001

Serious events: 35 serious events

Other events: 39 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Avastin + RAD001 n=39 participants at risk One agent (RAD001 or Avastin) then adding the second agent (Avastin or RAD001): Avastin 15 mg/kg intravenous (IV) every 3 weeks + RAD001 10 mg orally daily for 21 Days
Metabolism and nutrition disorders ALT ELEVATION	5.1% 2/39 • 2 years and 1 month Adverse Events reported as whole participant group regardless of the agent order received since all patients received both RAD001 and Avastin after one cycle (3 week) of receiving either RAD001 or Avastin per randomization.
Blood and lymphatic system disorders ANEMIA	5.1% 2/39 • 2 years and 1 month Adverse Events reported as whole participant group regardless of the agent order received since all patients received both RAD001 and Avastin after one cycle (3 week) of receiving either RAD001 or Avastin per randomization.
Metabolism and nutrition disorders AST ELEVATION	7.7% 3/39 • 2 years and 1 month Adverse Events reported as whole participant group regardless of the agent order received since all patients received both RAD001 and Avastin after one cycle (3 week) of receiving either RAD001 or Avastin per randomization.
General disorders FATIGUE	7.7% 3/39 • 2 years and 1 month Adverse Events reported as whole participant group regardless of the agent order received since all patients received both RAD001 and Avastin after one cycle (3 week) of receiving either RAD001 or Avastin per randomization.
Metabolism and nutrition disorders HYPERGLYCEMIA	10.3% 4/39 • 2 years and 1 month Adverse Events reported as whole participant group regardless of the agent order received since all patients received both RAD001 and Avastin after one cycle (3 week) of receiving either RAD001 or Avastin per randomization.
Infections and infestations INFECTION	7.7% 3/39 • 2 years and 1 month Adverse Events reported as whole participant group regardless of the agent order received since all patients received both RAD001 and Avastin after one cycle (3 week) of receiving either RAD001 or Avastin per randomization.
Gastrointestinal disorders NAUSEA	5.1% 2/39 • 2 years and 1 month Adverse Events reported as whole participant group regardless of the agent order received since all patients received both RAD001 and Avastin after one cycle (3 week) of receiving either RAD001 or Avastin per randomization.
Blood and lymphatic system disorders NEUTROPENIA	12.8% 5/39 • 2 years and 1 month Adverse Events reported as whole participant group regardless of the agent order received since all patients received both RAD001 and Avastin after one cycle (3 week) of receiving either RAD001 or Avastin per randomization.
Metabolism and nutrition disorders PROTEINURIA	12.8% 5/39 • 2 years and 1 month Adverse Events reported as whole participant group regardless of the agent order received since all patients received both RAD001 and Avastin after one cycle (3 week) of receiving either RAD001 or Avastin per randomization.
Blood and lymphatic system disorders THROMBOCYTOPENIA	5.1% 2/39 • 2 years and 1 month Adverse Events reported as whole participant group regardless of the agent order received since all patients received both RAD001 and Avastin after one cycle (3 week) of receiving either RAD001 or Avastin per randomization.
Gastrointestinal disorders VOMITING	5.1% 2/39 • 2 years and 1 month Adverse Events reported as whole participant group regardless of the agent order received since all patients received both RAD001 and Avastin after one cycle (3 week) of receiving either RAD001 or Avastin per randomization.
Gastrointestinal disorders WEIGHT LOSS	5.1% 2/39 • 2 years and 1 month Adverse Events reported as whole participant group regardless of the agent order received since all patients received both RAD001 and Avastin after one cycle (3 week) of receiving either RAD001 or Avastin per randomization.

Other adverse events

Other adverse events
Measure	Avastin + RAD001 n=39 participants at risk One agent (RAD001 or Avastin) then adding the second agent (Avastin or RAD001): Avastin 15 mg/kg intravenous (IV) every 3 weeks + RAD001 10 mg orally daily for 21 Days
Metabolism and nutrition disorders ALT ELEVATION	12.8% 5/39 • 2 years and 1 month Adverse Events reported as whole participant group regardless of the agent order received since all patients received both RAD001 and Avastin after one cycle (3 week) of receiving either RAD001 or Avastin per randomization.
Blood and lymphatic system disorders ANEMIA	33.3% 13/39 • 2 years and 1 month Adverse Events reported as whole participant group regardless of the agent order received since all patients received both RAD001 and Avastin after one cycle (3 week) of receiving either RAD001 or Avastin per randomization.
Gastrointestinal disorders ANOREXIA	35.9% 14/39 • 2 years and 1 month Adverse Events reported as whole participant group regardless of the agent order received since all patients received both RAD001 and Avastin after one cycle (3 week) of receiving either RAD001 or Avastin per randomization.
Metabolism and nutrition disorders AST ELEVATION	15.4% 6/39 • 2 years and 1 month Adverse Events reported as whole participant group regardless of the agent order received since all patients received both RAD001 and Avastin after one cycle (3 week) of receiving either RAD001 or Avastin per randomization.
Respiratory, thoracic and mediastinal disorders COUGH	17.9% 7/39 • 2 years and 1 month Adverse Events reported as whole participant group regardless of the agent order received since all patients received both RAD001 and Avastin after one cycle (3 week) of receiving either RAD001 or Avastin per randomization.
Gastrointestinal disorders DIARRHEA	48.7% 19/39 • 2 years and 1 month Adverse Events reported as whole participant group regardless of the agent order received since all patients received both RAD001 and Avastin after one cycle (3 week) of receiving either RAD001 or Avastin per randomization.
General disorders DIZZINESS	17.9% 7/39 • 2 years and 1 month Adverse Events reported as whole participant group regardless of the agent order received since all patients received both RAD001 and Avastin after one cycle (3 week) of receiving either RAD001 or Avastin per randomization.
Nervous system disorders DYSGEUSIA	12.8% 5/39 • 2 years and 1 month Adverse Events reported as whole participant group regardless of the agent order received since all patients received both RAD001 and Avastin after one cycle (3 week) of receiving either RAD001 or Avastin per randomization.
Respiratory, thoracic and mediastinal disorders DYSPNEA	23.1% 9/39 • 2 years and 1 month Adverse Events reported as whole participant group regardless of the agent order received since all patients received both RAD001 and Avastin after one cycle (3 week) of receiving either RAD001 or Avastin per randomization.
General disorders EDEMA	46.2% 18/39 • 2 years and 1 month Adverse Events reported as whole participant group regardless of the agent order received since all patients received both RAD001 and Avastin after one cycle (3 week) of receiving either RAD001 or Avastin per randomization.
Respiratory, thoracic and mediastinal disorders EPISTAXIS	64.1% 25/39 • 2 years and 1 month Adverse Events reported as whole participant group regardless of the agent order received since all patients received both RAD001 and Avastin after one cycle (3 week) of receiving either RAD001 or Avastin per randomization.
General disorders FATIGUE	61.5% 24/39 • 2 years and 1 month Adverse Events reported as whole participant group regardless of the agent order received since all patients received both RAD001 and Avastin after one cycle (3 week) of receiving either RAD001 or Avastin per randomization.
General disorders FEVER	23.1% 9/39 • 2 years and 1 month Adverse Events reported as whole participant group regardless of the agent order received since all patients received both RAD001 and Avastin after one cycle (3 week) of receiving either RAD001 or Avastin per randomization.
Gastrointestinal disorders FLATULENCE	12.8% 5/39 • 2 years and 1 month Adverse Events reported as whole participant group regardless of the agent order received since all patients received both RAD001 and Avastin after one cycle (3 week) of receiving either RAD001 or Avastin per randomization.
Nervous system disorders HEADACHE	28.2% 11/39 • 2 years and 1 month Adverse Events reported as whole participant group regardless of the agent order received since all patients received both RAD001 and Avastin after one cycle (3 week) of receiving either RAD001 or Avastin per randomization.
Metabolism and nutrition disorders HYPERGLYCEMIA	43.6% 17/39 • 2 years and 1 month Adverse Events reported as whole participant group regardless of the agent order received since all patients received both RAD001 and Avastin after one cycle (3 week) of receiving either RAD001 or Avastin per randomization.
Cardiac disorders HYPERTENSION	51.3% 20/39 • 2 years and 1 month Adverse Events reported as whole participant group regardless of the agent order received since all patients received both RAD001 and Avastin after one cycle (3 week) of receiving either RAD001 or Avastin per randomization.
Metabolism and nutrition disorders HYPERTRIGLYCERIDEMIA	51.3% 20/39 • 2 years and 1 month Adverse Events reported as whole participant group regardless of the agent order received since all patients received both RAD001 and Avastin after one cycle (3 week) of receiving either RAD001 or Avastin per randomization.
Metabolism and nutrition disorders HYPOMAGNESEMIA	15.4% 6/39 • 2 years and 1 month Adverse Events reported as whole participant group regardless of the agent order received since all patients received both RAD001 and Avastin after one cycle (3 week) of receiving either RAD001 or Avastin per randomization.
Metabolism and nutrition disorders HYPOPHOSPHATEMIA	15.4% 6/39 • 2 years and 1 month Adverse Events reported as whole participant group regardless of the agent order received since all patients received both RAD001 and Avastin after one cycle (3 week) of receiving either RAD001 or Avastin per randomization.
Infections and infestations INFECTION	56.4% 22/39 • 2 years and 1 month Adverse Events reported as whole participant group regardless of the agent order received since all patients received both RAD001 and Avastin after one cycle (3 week) of receiving either RAD001 or Avastin per randomization.
General disorders INSOMNIA	15.4% 6/39 • 2 years and 1 month Adverse Events reported as whole participant group regardless of the agent order received since all patients received both RAD001 and Avastin after one cycle (3 week) of receiving either RAD001 or Avastin per randomization.
Gastrointestinal disorders MUCOSITIS	61.5% 24/39 • 2 years and 1 month Adverse Events reported as whole participant group regardless of the agent order received since all patients received both RAD001 and Avastin after one cycle (3 week) of receiving either RAD001 or Avastin per randomization.
Gastrointestinal disorders NAIL CHANGE	23.1% 9/39 • 2 years and 1 month Adverse Events reported as whole participant group regardless of the agent order received since all patients received both RAD001 and Avastin after one cycle (3 week) of receiving either RAD001 or Avastin per randomization.
Gastrointestinal disorders NAUSEA	43.6% 17/39 • 2 years and 1 month Adverse Events reported as whole participant group regardless of the agent order received since all patients received both RAD001 and Avastin after one cycle (3 week) of receiving either RAD001 or Avastin per randomization.
Blood and lymphatic system disorders NEUTROPENIA	17.9% 7/39 • 2 years and 1 month Adverse Events reported as whole participant group regardless of the agent order received since all patients received both RAD001 and Avastin after one cycle (3 week) of receiving either RAD001 or Avastin per randomization.
Musculoskeletal and connective tissue disorders PERIPHERAL NEUROPATHY	17.9% 7/39 • 2 years and 1 month Adverse Events reported as whole participant group regardless of the agent order received since all patients received both RAD001 and Avastin after one cycle (3 week) of receiving either RAD001 or Avastin per randomization.
Metabolism and nutrition disorders PROTEINURIA	43.6% 17/39 • 2 years and 1 month Adverse Events reported as whole participant group regardless of the agent order received since all patients received both RAD001 and Avastin after one cycle (3 week) of receiving either RAD001 or Avastin per randomization.
Skin and subcutaneous tissue disorders SKIN RASH	15.4% 6/39 • 2 years and 1 month Adverse Events reported as whole participant group regardless of the agent order received since all patients received both RAD001 and Avastin after one cycle (3 week) of receiving either RAD001 or Avastin per randomization.
Blood and lymphatic system disorders THROMBOCYTOPENIA	20.5% 8/39 • 2 years and 1 month Adverse Events reported as whole participant group regardless of the agent order received since all patients received both RAD001 and Avastin after one cycle (3 week) of receiving either RAD001 or Avastin per randomization.
Gastrointestinal disorders VOMITING	28.2% 11/39 • 2 years and 1 month Adverse Events reported as whole participant group regardless of the agent order received since all patients received both RAD001 and Avastin after one cycle (3 week) of receiving either RAD001 or Avastin per randomization.
Gastrointestinal disorders WEIGHT LOSS	43.6% 17/39 • 2 years and 1 month Adverse Events reported as whole participant group regardless of the agent order received since all patients received both RAD001 and Avastin after one cycle (3 week) of receiving either RAD001 or Avastin per randomization.

Additional Information

Dr. James Yao

UT MD Anderson Cancer Center

Phone: 713-792-2828

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place