Erlotinib and Bevacizumab in Treating Patients With Stage IV Melanoma

NCT00466687 | Completed Phase 2 Results DMC

• 3 other identifiers: VICC MEL 0418VU-VICC-MEL-0418VU-IRB-040468
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 4

Brief Summary

RATIONALE: Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving erlotinib together with bevacizumab may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving erlotinib together with bevacizumab works in treating patients with stage IV melanoma.

Conditions

Melanoma

Keywords

stage IV melanoma; recurrent melanoma

Outcome Measures

Primary Outcomes (1)

• Number of Patients With Response

  Per Response Evaluation Criteria in Solid Tumor (RECIST): Progressive disease (PD): \>=20% increase in sum of longest diameter (LD) of target lesion(s), taking as reference smallest sum LD recorded since treatment started. Complete response (CR): disappearance of all target lesions. Partial response (PR): \>=30% decrease in sum of LD of target lesion(s), taking as reference baseline sum LD. Stable disease (SD): neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD.

  At 6 months

Secondary Outcomes (3)

• Time to Disease Progression.

  up to one year after off-study date

• Progression-free Survival at 6 Months

  6 months

• Number of Patients With Each Worst-grade Toxicity Response

  Day 1 of each 28-day cycle for 6 cycles (168 days)

Study Arms (1)

Therapeutic Intervention

EXPERIMENTAL

Tarceva and Avastin: * Tarceva: 150mg PO, days 1-28 * Avastin: 10mg/kg, IV infusion, days 1,15 Regimen will be repeated every 28 days = 1 course

Biological: bevacizumab; Drug: erlotinib hydrochloride; Genetic: fluorescence in situ hybridization; Genetic: gene expression analysis; Other: immunologic technique; Other: laboratory biomarker analysis; Procedure: biopsy

Interventions

bevacizumab BIOLOGICAL

10mg/kg, slow IV infusion, Days 1 and 14

Also known as: Avastin

Therapeutic Intervention

erlotinib hydrochloride DRUG

150mg PO qd

Also known as: Tarceva

Therapeutic Intervention

fluorescence in situ hybridization GENETIC

Targeting multiple genetic aberrations in isolated tumor cells.

Therapeutic Intervention

gene expression analysis GENETIC

gene expression analysis

Therapeutic Intervention

immunologic technique OTHER

immunologic technique

Therapeutic Intervention

laboratory biomarker analysis OTHER

laboratory biomarker analysis

Therapeutic Intervention

biopsy PROCEDURE

biopsy

Therapeutic Intervention

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Measurable Stage IV melanoma
• Easter Cooperative Oncology Group (ECOG) Performance Status must be 0-1
• Good organ function as demonstrated by, Creatinine \<2.mg/dl, AST or ALT \<5 times upper limit of normal for subjects with documented liver metastases; \<2.5 times the upper limit of normal (ULN) for subjects without evidence of liver metastases, bilirubin\<2.0mg/dl,, absolute neutrophil count (ANC)\>1500/ul, platelets\>75k/ul, hemoglobin (Hgb)\>9 (may be transfused to obtain)
• Prior therapy: adjuvant interferon (IFN) allowed; no more than one prior regimen for advanced stage IV disease
• Patients must have a life expectancy of \>3 months
• Patients with brain metastases are eligible only if they fulfill the following: resected or stereotactic treatment a minimum of 3 months previously and no active CNS disease since then; brain metastases treated greater than 6 months ago without evidence of progression or hemorrhage, \<1cm in size per lesion (up to 3 lesions), and off all steroids
• Patients may not have received other agents, either investigational or marketed, which act by either EGFr inhibition or anti-angiogenesis mechanisms. Other epidermal growth factor receptor (EGFR) inhibitors include (but are not limited to): Iressa, erbitux, CI-1033. Angiogenesis inhibitors include (but are not limited to): SU5416, SU6668, SU 0122348, CP547632, VEGF Trap, anti-integrin αVβ3.
• Recovered from toxicity of major surgery (4 wks), chemotherapy or biologic therapy (4 wks), and/or radiation therapy (2 wks)
• No active other malignancy within 12 months
• No active systemic infection
• Over age of 18 years and signed IRB approved informed consent

You may not qualify if:

• Subjects meeting any of the following criteria (3.2.2-3.2.16) are ineligible for study entry
• Compromised renal or hepatic function as defined by Creatinine \>2.0mg/dl, aspartate transaminase (AST) or alanine transaminase (ALT) \>5 times upper limit of normal for subjects with documented liver metastases; \>2.5 times the upper limit of normal (ULN) for subjects without evidence of liver metastases
• Patient may not be part of any other investigational studies
• internationalized normal ratio (INR) \> 1.5
• Patients with PEG or G-tube are ineligible.
• Major surgical procedure, open biopsy; or significant traumatic injury within 28 days, or anticipation of need for major surgical procedure during the course of the study
• Any non-healing wound, ulcer, or bone fracture.
• Any clinical evidence or history of a bleeding diathesis or coagulopathy.
• Patients with a history of deep vein thrombosis or thromboembolic disease within the past 6 months.
• History of acute myocardial infarction within 6 months. In addition, patients are ineligible if they have clinically significant cardiovascular disease ((e.g., uncontrolled hypertension \[blood pressure of \>160/110 mmHg on medication\], New York Heart Association (NYHA) Grade II or greater congestive heart failure, serious cardiac dysrhythmia requiring medication, or peripheral vascular disease (Grade II or greater)
• Patients with \> 1+ proteinuria will have 24-hour urine collection; for protein. Patients with ≥ 1gm protein/24 hrs will be excluded
• If child bearing age must not be pregnant or nursing and use methods to prevent pregnancy
• History or evidence upon physical examination of central nervous system (CNS) disease (e.g., primary brain tumor, seizures not controlled with standard medical therapy, or history of stroke)
• Inability to comply with study and/or follow-up procedures
• History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect the interpretation of the results of the study or render the subject at high risk from treatment complications.

Sponsors & Collaborators

• Vanderbilt-Ingram Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (4)

Vanderbilt-Ingram Cancer Center - Cool Springs

Nashville, Tennessee, 37067-1631, United States

Location

Vanderbilt-Ingram Cancer Center at Franklin

Nashville, Tennessee, 37067, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232-6838, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

Bevacizumab; Erlotinib Hydrochloride; In Situ Hybridization, Fluorescence; Gene Expression Profiling; Immunologic Techniques; Biopsy

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; In Situ Hybridization; Staining and Labeling; Histocytological Preparation Techniques; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Histological Techniques; Investigative Techniques; Cytogenetic Analysis; Genetic Techniques; Nucleic Acid Hybridization; Cytodiagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative

Results Point of Contact

• Title: Jeffrey Sosman, M.D.
• Organization: Vanderbilt-Ingram Cancer Center

jeff.sosman@vanderbilt.edu

Study Officials

• Jeffrey A. Sosman, MD

  Vanderbilt-Ingram Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine; Director, Melanoma and Tumor Immunotherapy

Study Record Dates

• First Submitted: April 25, 2007
• First Posted: April 27, 2007
• Study Start: September 1, 2004
• Primary Completion: August 1, 2008
• Study Completion: September 1, 2008
• Last Updated: July 22, 2013
• Results First Posted: February 28, 2013

Record last verified: 2013-07

Locations

US (4)