RAD001 Plus Bevacizumab in Metastatic Melanoma

• ClinicalTrials.gov Identifier: NCT00591734
• Recruitment Status: Completed
• First Posted: January 11, 2008
• Results First Posted: February 26, 2013
• Last Update Posted: November 24, 2021
• Sponsor: SCRI Development Innovations, LLC
• Collaborators: Genentech, Inc.; Novartis
• Information provided by (Responsible Party): SCRI Development Innovations, LLC

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Metastatic Melanoma	Drug: Bevacizumab; Drug: Everolimus	Phase 2

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 57 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Trial of RAD001 Plus Bevacizumab in the Treatment of Patients With Metastatic Melanoma
• Study Start Date: January 2008
• Actual Primary Completion Date: October 2010
• Actual Study Completion Date: October 2011

Arms and Interventions

Arm	Intervention/treatment
Experimental: Intervention; All patients received bevacizumab 15 mg/kg, administered by intravenous (IV) infusion on day 1 of each 21 day course. In addition, patients received everolimus 10 mg orally on a daily basis.	Drug: Bevacizumab; 15 mg/kg of bevacizumab intravenously (IV) once every 3 weeks.; Other Name: Avastin; Drug: Everolimus; 10 mg by mouth daily; Other Names: Afinitor; RAD001

Outcome Measures

Primary Outcome Measures :

1. Progression-free Survival [ Time Frame: 13 months ]
   Length of time, in months, that patients were alive from their first date of protocol treatment until worsening of their disease

Secondary Outcome Measures :

1. Overall Survival Rate [ Time Frame: 1 year ]
   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.
2. Objective Response Rate (ORR) [ Time Frame: 13 months ]
   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.

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:

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).

Contacts and Locations

Locations

United States, Florida

Florida Cancer Specialists

Fort Myers, Florida, United States, 33901

Watson Clinic Center for Cancer Care and Research

Lakeland, Florida, United States, 33805

Florida Hospital Cancer Institute

Orlando, Florida, United States, 32804

Gulfcoast Oncology Associates

Saint Petersburg, Florida, United States, 33705

United States, Georgia

Northeast Georgia Medical Center

Gainesville, Georgia, United States, 30501

United States, Indiana

Oncology Hematology Associates of SW Indiana

Evansville, Indiana, United States, 47714

United States, Maryland

Center for Cancer and Blood Disorders

Bethesda, Maryland, United States, 20817

United States, Michigan

Grand Rapids Clinical Oncology Program

Grand Rapids, Michigan, United States, 49503

United States, Missouri

St. Louis Cancer Care

Chesterfield, Missouri, United States, 63017

United States, Nebraska

Methodist Cancer Center

Omaha, Nebraska, United States, 68114

United States, Pennsylvania

Consultants in Medical Oncology and Hematology

Drexel Hill, Pennsylvania, United States, 19026

United States, Tennessee

Chattanooga Oncology & Hematology Associates

Chattanooga, Tennessee, United States, 37404

Tennessee Oncology, PLLC

Nashville, Tennessee, United States, 37023

United States, Texas

South Texas Oncology and Hematology

San Antonio, Texas, United States, 78258

United States, Virginia

Virginia Cancer Institute

Richmond, Virginia, United States, 23235

Sponsors and Collaborators

SCRI Development Innovations, LLC

Genentech, Inc.

Novartis

Investigators

• Study Chair: John D. Hainsworth, M.D.; SCRI Development Innovations, LLC

More Information

Publications of Results:

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.

• Responsible Party: SCRI Development Innovations, LLC
• ClinicalTrials.gov Identifier: NCT00591734
• Other Study ID Numbers: SCRI MEL 16
• First Posted: January 11, 2008
• Results First Posted: February 26, 2013
• Last Update Posted: November 24, 2021
• Last Verified: November 2021

Keywords provided by SCRI Development Innovations, LLC:

Metastatic Melanoma; Everolimus; RAD001; Bevacizumab

Additional relevant MeSH terms:

Melanoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Bevacizumab; Everolimus; Antineoplastic Agents, Immunological; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Growth Inhibitors; Immunosuppressive Agents; Immunologic Factors