Clinical trial NCT00591734: RAD001 Plus Bevacizumab in Metastatic Melanoma
Official title: A Phase II Trial of RAD001 Plus Bevacizumab in the Treatment of Patients With Metastatic Melanoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Melanoma
Keywords: Metastatic Melanoma
Everolimus
RAD001
Bevacizumab
Lead sponsor: SCRI Development Innovations, LLC
Sponsor class: OTHER
Collaborators: name: Genentech, Inc.
name: Novartis
First posted: 2008-01-11
Enrollment: 57
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Detailed 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

Eligibility criteria: 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).

Primary outcomes:
measure: Progression-free Survival
timeFrame: 13 months
Secondary outcomes:
measure: Overall Survival Rate
timeFrame: 1 year
measure: Objective Response Rate (ORR)
timeFrame: 13 months
Other outcomes:
Locations:
city: Fort Myers
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Lakeland
country: United States
facility: Watson Clinic Center for Cancer Care and Research
state: Florida
city: Orlando
country: United States
facility: Florida Hospital Cancer Institute
state: Florida
city: Saint Petersburg
country: United States
facility: Gulfcoast Oncology Associates
state: Florida
city: Gainesville
country: United States
facility: Northeast Georgia Medical Center
state: Georgia
city: Evansville
country: United States
facility: Oncology Hematology Associates of SW Indiana
state: Indiana
city: Bethesda
country: United States
facility: Center for Cancer and Blood Disorders
state: Maryland
city: Grand Rapids
country: United States
facility: Grand Rapids Clinical Oncology Program
state: Michigan
city: Chesterfield
country: United States
facility: St. Louis Cancer Care
state: Missouri
city: Omaha
country: United States
facility: Methodist Cancer Center
state: Nebraska
city: Drexel Hill
country: United States
facility: Consultants in Medical Oncology and Hematology
state: Pennsylvania
city: Chattanooga
country: United States
facility: Chattanooga Oncology & Hematology Associates
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: San Antonio
country: United States
facility: South Texas Oncology and Hematology
state: Texas
city: Richmond
country: United States
facility: Virginia Cancer Institute
state: Virginia
Study officials:
affiliation: SCRI Development Innovations, LLC
name: John D. Hainsworth, M.D.
role: STUDY_CHAIR
References:
citation: 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 Consortium. Cancer. 2010 Sep 1;116(17):4122-9. doi: 10.1002/cncr.25320.