Trial Outcomes & Findings for Expanded Cohort for Metastatic Colorectal Cancer (MCRC) Using Bevacizumab + Everolimus (NCT NCT00597506)

Last Updated: 2012-12-27

Results Overview

Overall response is composed of complete responses and partial responses. Complete response (CR): disappearance of all target lesions; Partial response: at least a 30 percent decrease in the sum of the longest diameter of the target lesions taking as reference the baseline sum longest diameter. Response is assessed at each subject's restaging, approximately ever 2 months.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

50 participants

Primary outcome timeframe

Measured 1 month after the last treated subject came off treatment

Results posted on

2012-12-27

Participant Flow

The recruitment process started in October 2007 and was complete in April 2009. All subjects except one were enrolled at the Morris Cancer Clinic at Duke University Medical Center. One subject was enrolled at the Community Memorial Healthcenter in South Hill, Virgina which is a Duke Oncology Network clinical research site.

Participant milestones

Participant milestones
Measure	Drug: Bevacizumab and Everolimus Open-label, non-randomized expanded cohort trial of refractory metastatic colorectal cancer subjects treated on 28 day cycles with the following treatment regimen: 10 mg/kg intravenous bevacizumab on days 1 and 15 each cycle and 10 mg everolimus(RAD001) daily by mouth.
Overall Study STARTED	50
Overall Study COMPLETED	49
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Drug: Bevacizumab and Everolimus Open-label, non-randomized expanded cohort trial of refractory metastatic colorectal cancer subjects treated on 28 day cycles with the following treatment regimen: 10 mg/kg intravenous bevacizumab on days 1 and 15 each cycle and 10 mg everolimus(RAD001) daily by mouth.
Overall Study Subject is being followed for survival	1

Baseline Characteristics

Expanded Cohort for Metastatic Colorectal Cancer (MCRC) Using Bevacizumab + Everolimus

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Bevacizumab and Everolimus n=50 Participants Expanded Cohort of Patients with Refractory Metastatic Colorectal Cancer Treated With Bevacizumab and Everolimus
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	40 Participants n=5 Participants
Age, Categorical >=65 years	10 Participants n=5 Participants
Age Continuous	56 years STANDARD_DEVIATION 10.8 • n=5 Participants
Sex: Female, Male Female	20 Participants n=5 Participants
Sex: Female, Male Male	30 Participants n=5 Participants
Region of Enrollment United States	50 participants n=5 Participants

PRIMARY outcome

Timeframe: Measured 1 month after the last treated subject came off treatment

Population: 50 patients were enrolled and received bevacizumab at 10mg/kg every 2 weeks and everolimus at 10mg orally daily. However, only 49 patients were evaluable for progression. One patient who received less than 1 cycle of the regimen and died from a non-treatment-related illness was not included in the analysis.

Outcome measures

Outcome measures
Measure	Bevacizumab and Everolimus n=49 Participants Enrolled participants on research study received bevacizumab at 10mg/kg every 2 weeks (day 1 and day 15 of each 28 day cycle) and everolimus at 10mg orally daily
Overall Response	0 percentage of participants

PRIMARY outcome

Timeframe: interval between start of treatment and 8-week

8 week PFS

Outcome measures

Outcome measures
Measure	Bevacizumab and Everolimus n=49 Participants Enrolled participants on research study received bevacizumab at 10mg/kg every 2 weeks (day 1 and day 15 of each 28 day cycle) and everolimus at 10mg orally daily
Progression Free Survival (PFS)	0.58 proportion of participants Interval 0.46 to 0.68

Adverse Events

Bevacizumab and Everolimus

Serious events: 27 serious events

Other events: 48 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Bevacizumab and Everolimus n=50 participants at risk Expanded Cohort of Patients with Refractory Metastatic Colorectal Cancer Treated With Bevacizumab and Everolimus
Gastrointestinal disorders Dehydration	4.0% 2/50 • Number of events 4 • Adverse events were collected from 26Oct2007 (date of enrollment of first subject) through 17 April2010 (30 days after the last subject completed study drug).
Gastrointestinal disorders Enterovesicular fistula	2.0% 1/50 • Number of events 1 • Adverse events were collected from 26Oct2007 (date of enrollment of first subject) through 17 April2010 (30 days after the last subject completed study drug).
Gastrointestinal disorders Bowel Perforation	2.0% 1/50 • Number of events 1 • Adverse events were collected from 26Oct2007 (date of enrollment of first subject) through 17 April2010 (30 days after the last subject completed study drug).
Gastrointestinal disorders Hemorrhage, GI rectum	2.0% 1/50 • Number of events 1 • Adverse events were collected from 26Oct2007 (date of enrollment of first subject) through 17 April2010 (30 days after the last subject completed study drug).
Metabolism and nutrition disorders Hyponatremia	2.0% 1/50 • Number of events 1 • Adverse events were collected from 26Oct2007 (date of enrollment of first subject) through 17 April2010 (30 days after the last subject completed study drug).
Gastrointestinal disorders Abdominal abscess with anastomatic leak	2.0% 1/50 • Number of events 1 • Adverse events were collected from 26Oct2007 (date of enrollment of first subject) through 17 April2010 (30 days after the last subject completed study drug).
Musculoskeletal and connective tissue disorders Rhabdomyolysis	2.0% 1/50 • Number of events 1 • Adverse events were collected from 26Oct2007 (date of enrollment of first subject) through 17 April2010 (30 days after the last subject completed study drug).
Metabolism and nutrition disorders Hyperbilirubinemia	2.0% 1/50 • Number of events 1 • Adverse events were collected from 26Oct2007 (date of enrollment of first subject) through 17 April2010 (30 days after the last subject completed study drug).
Infections and infestations Hypoxia	2.0% 1/50 • Number of events 1 • Adverse events were collected from 26Oct2007 (date of enrollment of first subject) through 17 April2010 (30 days after the last subject completed study drug).
General disorders Pain	2.0% 1/50 • Number of events 1 • Adverse events were collected from 26Oct2007 (date of enrollment of first subject) through 17 April2010 (30 days after the last subject completed study drug).
General disorders Shortness of breath/chest pain	2.0% 1/50 • Number of events 1 • Adverse events were collected from 26Oct2007 (date of enrollment of first subject) through 17 April2010 (30 days after the last subject completed study drug).
Gastrointestinal disorders Small bowel obstruction and pain	2.0% 1/50 • Number of events 1 • Adverse events were collected from 26Oct2007 (date of enrollment of first subject) through 17 April2010 (30 days after the last subject completed study drug).
Cardiac disorders atrial fibrillation	2.0% 1/50 • Number of events 1 • Adverse events were collected from 26Oct2007 (date of enrollment of first subject) through 17 April2010 (30 days after the last subject completed study drug).
Infections and infestations Infection	2.0% 1/50 • Number of events 1 • Adverse events were collected from 26Oct2007 (date of enrollment of first subject) through 17 April2010 (30 days after the last subject completed study drug).
Cardiac disorders Cardiopulmonary arrest	2.0% 1/50 • Number of events 1 • Adverse events were collected from 26Oct2007 (date of enrollment of first subject) through 17 April2010 (30 days after the last subject completed study drug).
General disorders Abdominal pain	4.0% 2/50 • Number of events 2 • Adverse events were collected from 26Oct2007 (date of enrollment of first subject) through 17 April2010 (30 days after the last subject completed study drug).
Respiratory, thoracic and mediastinal disorders Dyspnea	2.0% 1/50 • Number of events 1 • Adverse events were collected from 26Oct2007 (date of enrollment of first subject) through 17 April2010 (30 days after the last subject completed study drug).
Gastrointestinal disorders Aspiration	2.0% 1/50 • Number of events 1 • Adverse events were collected from 26Oct2007 (date of enrollment of first subject) through 17 April2010 (30 days after the last subject completed study drug).
Gastrointestinal disorders Anorexia	2.0% 1/50 • Number of events 1 • Adverse events were collected from 26Oct2007 (date of enrollment of first subject) through 17 April2010 (30 days after the last subject completed study drug).
General disorders Chest pain	2.0% 1/50 • Number of events 1 • Adverse events were collected from 26Oct2007 (date of enrollment of first subject) through 17 April2010 (30 days after the last subject completed study drug).
Gastrointestinal disorders Disease progression/Death	2.0% 1/50 • Number of events 1 • Adverse events were collected from 26Oct2007 (date of enrollment of first subject) through 17 April2010 (30 days after the last subject completed study drug).
Gastrointestinal disorders Dysphagia	2.0% 1/50 • Number of events 2 • Adverse events were collected from 26Oct2007 (date of enrollment of first subject) through 17 April2010 (30 days after the last subject completed study drug).
Metabolism and nutrition disorders Acute Renal failure	2.0% 1/50 • Number of events 1 • Adverse events were collected from 26Oct2007 (date of enrollment of first subject) through 17 April2010 (30 days after the last subject completed study drug).
Gastrointestinal disorders Vomiting	2.0% 1/50 • Number of events 2 • Adverse events were collected from 26Oct2007 (date of enrollment of first subject) through 17 April2010 (30 days after the last subject completed study drug).
Gastrointestinal disorders Diarrhea	2.0% 1/50 • Number of events 2 • Adverse events were collected from 26Oct2007 (date of enrollment of first subject) through 17 April2010 (30 days after the last subject completed study drug).

Other adverse events

Other adverse events
Measure	Bevacizumab and Everolimus n=50 participants at risk Expanded Cohort of Patients with Refractory Metastatic Colorectal Cancer Treated With Bevacizumab and Everolimus
Metabolism and nutrition disorders Hypokalemia	14.0% 7/50 • Adverse events were collected from 26Oct2007 (date of enrollment of first subject) through 17 April2010 (30 days after the last subject completed study drug).
Metabolism and nutrition disorders Hyperglycemia	12.0% 6/50 • Adverse events were collected from 26Oct2007 (date of enrollment of first subject) through 17 April2010 (30 days after the last subject completed study drug).
Metabolism and nutrition disorders Alkaline phosphatase elevation	12.0% 6/50 • Adverse events were collected from 26Oct2007 (date of enrollment of first subject) through 17 April2010 (30 days after the last subject completed study drug).
Gastrointestinal disorders Mucositis/Proctitis	74.0% 37/50 • Adverse events were collected from 26Oct2007 (date of enrollment of first subject) through 17 April2010 (30 days after the last subject completed study drug).
Metabolism and nutrition disorders Hyperlipidemia	68.0% 34/50 • Adverse events were collected from 26Oct2007 (date of enrollment of first subject) through 17 April2010 (30 days after the last subject completed study drug).
Cardiac disorders Hypertension	18.0% 9/50 • Adverse events were collected from 26Oct2007 (date of enrollment of first subject) through 17 April2010 (30 days after the last subject completed study drug).

Additional Information

Herbert Hurwitz, MD

Duke University Medical Center

Phone: 919-668-1861

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place