Erlotinib and Bevacizumab in Treating Patients With Stage IV Melanoma

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Jeffrey A. Sosman, MD, Vanderbilt-Ingram Cancer Center
ClinicalTrials.gov Identifier:
NCT00466687
First received: April 25, 2007
Last updated: July 15, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention Phase
Melanoma
Biological: bevacizumab
Drug: erlotinib hydrochloride
Genetic: fluorescence in situ hybridization
Genetic: gene expression analysis
Other: immunologic technique
Other: laboratory biomarker analysis
Procedure: biopsy
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of Tarceva (Erlotinib) and Avastin (Bevacizumab) in the Treatment of Patients With Metastatic Melanoma

Resource links provided by NLM:


Further study details as provided by Vanderbilt-Ingram Cancer Center:

Primary Outcome Measures:
  • Number of Patients With Response [ Time Frame: At 6 months ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Time to Disease Progression. [ Time Frame: up to one year after off-study date ] [ Designated as safety issue: No ]
    Time from on study date to date of progression in months, if the progression happened in the patient. Disease progression is defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions with reference to the smallest sum LD since treatment began or the appearance of one or more new lesions.

  • Progression-free Survival at 6 Months [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Patients with Progression-free survival at 6 months

  • Number of Patients With Each Worst-grade Toxicity Response [ Time Frame: Day 1 of each 28-day cycle for 6 cycles (168 days) ] [ Designated as safety issue: Yes ]
    Number of patients with worst-grade toxicity at each of five grades following National Cancer Institute Common Toxicity Criteria with grade 1 = mild, grade 2 = moderate, grade 3 = severe, grade 4 = life-threatening/disabling, 5 = death.


Enrollment: 34
Study Start Date: September 2004
Study Completion Date: September 2008
Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Therapeutic Intervention

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
10mg/kg, slow IV infusion, Days 1 and 14
Other Name: Avastin
Drug: erlotinib hydrochloride
150mg PO qd
Other Name: Tarceva
Genetic: fluorescence in situ hybridization
Targeting multiple genetic aberrations in isolated tumor cells.
Other Name: fluorescence in situ hybridization
Genetic: gene expression analysis
gene expression analysis
Other Name: gene expression analysis
Other: immunologic technique
immunologic technique
Other Name: immunologic technique
Other: laboratory biomarker analysis
laboratory biomarker analysis
Other Name: laboratory biomarker analysis
Procedure: biopsy
biopsy
Other Name: biopsy

Detailed Description:

OBJECTIVES:

Primary

  • Determine the overall response rate, response duration, and frequency of progression-free survival at 6 months in patients with stage IV melanoma treated with erlotinib hydrochloride and bevacizumab.
  • Determine objective responses in patients treated with this regimen.

Secondary

  • Determine the overall safety and tolerability of this regimen in these patients.
  • Evaluate tissue blocks for EGFR by monoclonal antibody H11 (DAKO) or fluorescence in situ hybridization(FISH)7p12-specific probe-overexpression or amplification in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive oral erlotinib hydrochloride once daily on days 1-28 and bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Patients undergo tissue collection to analyze EGFR by monoclonal antibody H11 (DAKO) or fluorescence in situ hybridization (FISH) 7p12-specific probe-overexpression or amplification. Biological markers AKT, MAPK, p27, p21, CD13, CD34, and factor VIII are also measured.

After completion of study treatment, patients are followed periodically.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00466687

Locations
United States, Tennessee
Vanderbilt-Ingram Cancer Center - Cool Springs
Nashville, Tennessee, United States, 37067-1631
Vanderbilt-Ingram Cancer Center at Franklin
Nashville, Tennessee, United States, 37067
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232-6838
Sarah Cannon Research Institute
Nashville, Tennessee, United States, 37203
Sponsors and Collaborators
Vanderbilt-Ingram Cancer Center
Investigators
Principal Investigator: Jeffrey A. Sosman, MD Vanderbilt-Ingram Cancer Center
  More Information

No publications provided

Responsible Party: Jeffrey A. Sosman, MD, Professor of Medicine; Director, Melanoma and Tumor Immunotherapy, Vanderbilt-Ingram Cancer Center
ClinicalTrials.gov Identifier: NCT00466687     History of Changes
Other Study ID Numbers: VICC MEL 0418, VU-VICC-MEL-0418, VU-IRB-040468
Study First Received: April 25, 2007
Results First Received: June 2, 2011
Last Updated: July 15, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Vanderbilt-Ingram Cancer Center:
stage IV melanoma
recurrent melanoma

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
Erlotinib
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 20, 2014