RAD001 Plus Bevacizumab in Metastatic Melanoma

Metastatic Melanoma Clinical Trial

Official title:

A Phase II Trial of RAD001 Plus Bevacizumab in the Treatment of Patients With Metastatic Melanoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00591734
• Other study ID #: SCRI MEL 16
• Status: Completed
• Phase: Phase 2
• Start date: January 2008
• Est. completion date: October 2011

Study information

• Verified date: November 2021
• Source: SCRI Development Innovations, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a non-randomized, open label Phase II study comparing bevacizumab and everolimus in the treatment of metastatic melanoma.

Description:

All patients will begin treatment with the same doses of RAD001 and bevacizumab. Patients will receive 6 weeks of treatment, followed by re evaluation. Patients with objective response or stable disease will continue treatment until disease progression.

During the study, all patients will receive 10 mg of RAD001 orally daily and 15 mg/kg of bevacizumab intravenously (IV) once every 3 weeks.

Fifty-five patients will be enrolled in this multi-centered study

Recruitment information / eligibility

• Status: Completed
• Enrollment: 57
• Est. completion date: October 2011
• Est. primary completion date: October 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Histologically confirmed melanoma.

2. Unresectable stage IV disease, or recurrent disease with metastases.

3. Measurable disease (by Response Evaluation Criteria in Solid Tumors [RECIST]) or measurable skin lesions.

4. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2.

5. Life expectancy >=12 weeks.

6. Patients are allowed 0-2 prior treatment regimens containing chemotherapy and/or immunotherapy (interferon, interleukin 2).

7. Women of childbearing potential must have a negative serum pregnancy test with 7 days before beginning treatment.

8. Absolute neutrophil count (ANC) >=1500/µL, and platelets >=100,000/µL.

9. Serum creatinine <=2.0 mg/dL.

10. Serum bilirubin <=1.5 mg/dL institutional upper limit of normal (ULN); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <2.5 × ULN or <5 × ULN in patients with documented liver metastases.

Exclusion Criteria:

1. Previous treatment with bevacizumab or other anti-angiogenesis agents.

2. Previous treatment with mTOR inhibitors.

3. Drugs or substances known to be inhibitors or inducers of the isoenzyme CYP3A are not allowed.

4. Treatment with investigational agents within 4 weeks of study entry.

5. Treatment with more than two previous chemotherapy regimens.

6. Immunization with attenuated live vaccines within one week of study or anytime during study treatment period.

7. Female patients who are pregnant or breastfeeding.

8. Central nervous system (CNS) involvement by metastatic melanoma.

9. CNS disease (e.g., seizures not controlled with standard medical therapy, history of stroke).

10. Any severe and/or uncontrolled medical conditions or other conditions that could affect participation in the study such as:

• Severely impaired lung function.

• Uncontrolled diabetes as defined by fasting serum glucose >1.5 ULN,

• Any acute or chronic uncontrolled infection/disorder.

• Non-malignant medical illnesses that are uncontrolled or whose control may be jeopardize by the treatment with the study therapy.

• Any acute or chronic uncontrolled infection/disorder.

• Non-malignant medical illnesses that are uncontrolled or whose control may be jeopardize by the treatment with the study therapy.

• Liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis.

11. Acute myocardial infarction (MI) with the previous 6 months.

12. Clinically significant cardiovascular disease (e.g., uncontrolled hypertension, unstable angina, New York Heart Association [NYHA] Class II or greater congestive heart failure [CHF], serious cardiac arrhythmia requiring medication), or >= grade 2 vascular disease.

13. Clinical history of hemoptysis or hematemesis.

14. Clinical evidence or history of a bleeding diathesis or coagulopathy.

15. Major surgical procedures, fine-needle aspirations, or core biopsies with 7 days of starting treatment.

16. Patients with PEG tubes or G-tubes.

17. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of RAD001 (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).

18. Proteinuria at screening as demonstrated by either

1. Urine protein:creatinine (UPC) ratio >= 1.0 at screening OR

2. Urine dipstick for proteinuria >= 2+ (patients discovered to have >=2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate <= 1g of protein in 24 hours to be eligible).

Related Conditions & MeSH terms

• Melanoma
• Metastatic Melanoma

Intervention

Drug:
• Bevacizumab
15 mg/kg of bevacizumab intravenously (IV) once every 3 weeks.
• Everolimus
10 mg by mouth daily

Locations

Country	Name	City	State
United States	Center for Cancer and Blood Disorders	Bethesda	Maryland
United States	Chattanooga Oncology & Hematology Associates	Chattanooga	Tennessee
United States	St. Louis Cancer Care	Chesterfield	Missouri
United States	Consultants in Medical Oncology and Hematology	Drexel Hill	Pennsylvania
United States	Oncology Hematology Associates of SW Indiana	Evansville	Indiana
United States	Florida Cancer Specialists	Fort Myers	Florida
United States	Northeast Georgia Medical Center	Gainesville	Georgia
United States	Grand Rapids Clinical Oncology Program	Grand Rapids	Michigan
United States	Watson Clinic Center for Cancer Care and Research	Lakeland	Florida
United States	Tennessee Oncology, PLLC	Nashville	Tennessee
United States	Methodist Cancer Center	Omaha	Nebraska
United States	Florida Hospital Cancer Institute	Orlando	Florida
United States	Virginia Cancer Institute	Richmond	Virginia
United States	Gulfcoast Oncology Associates	Saint Petersburg	Florida
United States	South Texas Oncology and Hematology	San Antonio	Texas

Sponsors (3)

Lead Sponsor	Collaborator
SCRI Development Innovations, LLC	Genentech, Inc., Novartis

Country where clinical trial is conducted

United States, 

References & Publications (1)

Hainsworth JD, Infante JR, Spigel DR, Peyton JD, Thompson DS, Lane CM, Clark BL, Rubin MS, Trent DF, Burris HA 3rd. Bevacizumab and everolimus in the treatment of patients with metastatic melanoma: a phase 2 trial of the Sarah Cannon Oncology Research Con — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival	Length of time, in months, that patients were alive from their first date of protocol treatment until worsening of their disease	13 months
Secondary	Overall Survival Rate	Overall Survival is defined as the length of time, in months, that patients were alive from their first date of protocol treatment until death. For patients who were alive at the time of calculation, follow-up time was censored at date of last contact. The percentage of patients who were alive at 1 year is reported here. This was estimated using the Kaplan Meier method.	1 year
Secondary	Objective Response Rate (ORR)	The percentage of patients who experience an objective benefit from treatment (CR+PR). The response categories were assigned using RECIST criteria. Complete Response (CR) = Disappearance of all target lesions ; Partial Response (PR) = >=30% decrease in the sum of the longest diameter of target lesions.	13 months