Temozolomide Plus Bevacizumab in Patients With Metastatic Melanoma Involving the Central Nervous System

NCT01048554 | Completed Phase 2

• 1 other identifier: MEL0107
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 3

Brief Summary

This research is being done because melanoma in the brain is very difficult to treat because it does not respond to radiation or to chemotherapy, such as temozolomide. One of the reasons for this is that the melanoma can make chemicals that signal the brain to provide new blood vessels for the tumor. The main signal is called VEGF. Bevacizumab is an antibody that blocks VEGF. The investigators want to see if the combination of bevacizumab and temozolomide will stop the melanoma from growing.

Conditions

Melanoma

Keywords

Melanoma; Brain mets; Bevacizumab; Temozolomide; Avastin; Temodar; Melanoma with brain mets

Outcome Measures

Primary Outcomes (1)

• Primary Outcome Measures: one-year survival rate

  one year

Secondary Outcomes (1)

• Secondary Outcome Measures: response rate and safety profile

  one year

Study Arms (1)

Temozolomide/Bevacizumab

OTHER

Patients will be treated with a combination of temozolomide at 75 mg/m2/day for six continuous weeks, followed by a two-week rest period and bevacizumab 10 mg/kg every 2 weeks without interruption. Cycles will be repeated every 8 weeks. Patients will be restaged every 8 weeks.

Drug: Temozolomide; Drug: Bevacizumab

Interventions

Temozolomide DRUG

Temozolomide 75mg/m2 for six continuous weeks

Temozolomide/Bevacizumab

Bevacizumab DRUG

Bevacizumab 10mg/kg every 2 weeks without interruption

Temozolomide/Bevacizumab

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically or cytologically confirmed malignant melanoma and clinical evidence of metastatic disease to the brain. Mucosal and ocular melanomas are included.
• Untreated asymptomatic brain metastases ≤ 2 cm in maximal diameter, with mild or minimal edema, without associated hemorrhage or midline shift.
• Progressing brain metastases of any size, not amenable to surgical resection and/or progressing through radiation therapy but without evidence of active associated hemorrhage. Treatment with bevacizumab may not be initiated until 4 weeks after surgical resection or radiation therapy completion.
• Hemorrhagic metastases that have resolved after previous resection or radiation therapy do not exclude patients with new non-hemorrhagic metastases meeting the criteria described above from participating.
• Patients must have measurable metastases to the brain, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>10 mm in the brain MRI with gadolinium. For disease outside the brain, tumors must be \> 20 mm with conventional techniques or \> 10 mm with spiral CT scan. Measurable disease outside the brain is NOT required.
• Patients with any number of previous systemic therapies are eligible. Previous temozolomide treatment given on a different schedule is allowed, as long as it had not been given in combination with VEGF-targeting drugs.
• Age \> 18 years. Because no dosing or adverse event data are currently available on the use of bevacizumab in patients \<18 years of age, children are excluded from this study.
• Life expectancy of 8 weeks or greater.
• ECOG performance status \< 2 (Karnofsky \> 60%).
• Patients must have normal organ and marrow function as defined below:
• Leukocytes \> 3,000/µl
• Absolute neutrophil count \> 1,500/µl
• Platelets \> 100,000/µl
• Total Bilirubin \*\* Within institutional upper limit of normal
• AST(SGOT)/ALT(SGPT) \< 2.5 X institutional upper limit of normal

You may not qualify if:

• Subjects meeting any of the following criteria are ineligible for study entry:
• Inability to comply with study and/or follow-up procedures.
• Life expectancy of less than 8 weeks
• Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study other than this study.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to bevacizumab or temozolomide.
• Patients must not exhibit any clinical evidence of coagulopathy. The INR must be \< 1.5 and the values for PTT must be within normal limits. Anticoagulation is not allowed.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, untreated cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant women are excluded from this study because bevacizumab is an agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with bevacizumab, breastfeeding should be discontinued if the mother is treated with bevacizumab. These potential risks may also apply to other agents used in this study.
• Otherwise well HIV-positive patients will be permitted to enroll on this trial.
• Previous treatment with bevacizumab.
• Inadequately controlled hypertension (defined as systolic blood pressure 150 and/or diastolic blood pressure \> 100 mmHg on antihypertensive medications)
• Any prior history of hypertensive crisis or hypertensive encephalopathy
• New York Heart Association (NYHA) Grade II or greater congestive heart failure (see Appendix E)
• History of myocardial infarction or unstable angina within 6 months prior to study enrollment
• History of stroke or transient ischemic attack within 6 months prior to study enrollment

Sponsors & Collaborators

• Mt. Sinai Medical Center, Miami: lead
• Northern California Melanoma Center: collaborator

Study Sites (3)

Saint Mary's Medical Center, 6th Floor

San Francisco, California, 94117, United States

Location

The Angeles Clinic and Research Institute

Santa Monica, California, 90404, United States

Location

Mount Sinai Medical Center

Miami Beach, Florida, 33140, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

Temozolomide; Bevacizumab

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)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Jose Lutzky, MD

  Mt Sinai Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator Jose Lutzky, M.D.

Study Record Dates

• First Submitted: January 12, 2010
• First Posted: January 13, 2010
• Study Start: November 1, 2009
• Primary Completion: September 1, 2011
• Study Completion: September 1, 2011
• Last Updated: April 19, 2012

Record last verified: 2012-04

Locations

US (3)