MelanomaPhase 2MEL0107NCT01048554
Temozolomide Plus Bevacizumab in Patients With Metastatic Melanoma Involving the Central Nervous System
A Phase 2 study testing Temozolomide and Bevacizumab in people with Melanoma, run by Mt. Sinai Medical Center, Miami at 3 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Melanoma
- What is being tested?
- Temozolomide and Bevacizumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 3 sitesUnited States
- Study dates
- Nov 2009to Sep 2011
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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
- Creatinine* Within institutional upper limit of normal*
- If creatinine > upper limit of normal, a creatinine clearance >/= 60 ml/m2 is required
- Except for patients with known Gilbert's syndrome
- The effects of bevacizumab on the developing human fetus at the recommended therapeutic dose are unknown. For this reason and because the anti-angiogenic agent used in this trial may be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
- Concomitant use of steroids to treat cerebral edema is allowed.
- Ability to understand and the willingness to sign a written informed consent document.
Who cannot join
- Disease-Specific Exclusions Patients with metastatic disease to the brain not fitting the inclusion criteria. Patients with leptomeningeal disease are not excluded.
- General Medical Exclusions
- 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.
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- 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.
- Bevacizumab-Specific Exclusions
- 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
- Significant vascular disease (e.g., aortic aneurysm, aortic dissection)
- Symptomatic peripheral vascular disease
- Evidence of bleeding diathesis or coagulopathy
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment or anticipation of need for major surgical procedure during the course of the study
- Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to study enrollment
- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment
- Serious, non-healing wound, ulcer, or bone fracture
- Proteinuria at screening as demonstrated by either
- Urine protein:creatinine (UPC) ratio 1.0 at screening OR
- 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).
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Mount Sinai Medical Center
Miami Beach, Florida, 33140
Saint Mary's Medical Center, 6th Floor
San Francisco, California, 94117
The Angeles Clinic and Research Institute
Santa Monica, California, 90404
About this study
Official title: A Phase II Trial of Temozolomide Plus Bevacizumab in Patients With Metastatic Melanoma Involving the Central Nervous System
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.
Read the detailed description
This study proposes the use of a combination of temozolomide and bevacizumab in a carefully selected group of patients with metastatic melanoma to the brain. This combination has been tested in primary brain tumors and in melanoma not involving the brain. The 6-week on, 2-week off low-dose schedule proposed in this trial capitalizes on preclinical data demonstrating that temozolomide inhibits angiogenesis at low, non-toxic doses that correspond to the plasma concentrations achieved by an oral administration, a so-called 'metronomic' scheduling. The precise mechanism of its antiangiogenic action remains to be elucidated. This potential synergistic mechanism, together with the bulk of evidence for activity presented above suggests that the combination will be well-tolerated, safe and possibly more effective.
- Conditions
- Melanoma
- Being tested
- Temozolomide, Bevacizumab
- Keywords
- Melanoma, Brain mets, Bevacizumab, Temozolomide, Avastin, Temodar, Melanoma with brain mets
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TemozolomideDrug
Temozolomide 75mg/m2 for six continuous weeks
BevacizumabDrug
Bevacizumab 10mg/kg every 2 weeks without interruption
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Temozolomide; Drug: Bevacizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary Outcome Measures: one-year survival rate
Measured: one year
Secondary outcomes (1)
Secondary Outcome Measures: response rate and safety profile
Measured: one year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jan 2010 (estimated)
- Study startNov 2009
- Primary completionSep 2011
- Study completionSep 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MelanomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mt. Sinai Medical Center, Miami
- Sponsor type
- University, hospital or other
- Collaborators
- Northern California Melanoma Center
- Responsible party
- Principal investigator, Jose Lutzky, Mt. Sinai Medical Center, Miami
- Investigators
- Jose Lutzky, MD, Principal investigator, Mt Sinai Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01048554
- Sponsor's protocol ID
- MEL0107
- Acronym
- MEL0107
- Status last verified
- Apr 2012
- First submitted
- 12 Jan 2010
- Last updated
- 19 Apr 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Apr 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial of Temozolomide Plus Bevacizumab in Patients With Metastatic Melanoma Involving the Central Nervous System
- ClinicalTrials.gov ID
- NCT01048554
- Acronym / sponsor ID
- MEL0107 / MEL0107
- Conditions
- Melanoma
- Keywords
- Melanoma, Brain mets, Bevacizumab, Temozolomide, Avastin, Temodar, Melanoma with brain mets
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- Mt. Sinai Medical Center, MiamiUniversity, hospital or other
- Collaborators
- Northern California Melanoma Center
- Study start
- Nov 2009
- Primary completion
- Sep 2011 (actual)
- Study completion
- Sep 2011 (actual)
- First posted
- 13 Jan 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This study proposes the use of a combination of temozolomide and bevacizumab in a carefully selected group of patients with metastatic melanoma to the brain. This combination has been tested in primary brain tumors and in melanoma not involving the brain. The 6-week on, 2-week off low-dose schedule proposed in this trial capitalizes on preclinical data demonstrating that temozolomide inhibits angiogenesis at low, non-toxic doses that correspond to the plasma concentrations achieved by an oral administration, a so-called 'metronomic' scheduling. The precise mechanism of its antiangiogenic action remains to be elucidated. This potential synergistic mechanism, together with the bulk of evidence for activity presented above suggests that the combination will be well-tolerated, safe and possibly more effective.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Temozolomide/Bevacizumab | Other | Drug: Temozolomide, Drug: BevacizumabPatients 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. |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- 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.
Key exclusion criteria (28 listed)
- Disease-Specific Exclusions Patients with metastatic disease to the brain not fitting the inclusion criteria. Patients with leptomeningeal disease are not excluded.
- General Medical Exclusions
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TemozolomideTemozolomide 75mg/m2 for six continuous weeks | Drug | Temozolomide/Bevacizumab |
| BevacizumabBevacizumab 10mg/kg every 2 weeks without interruption | Drug | Temozolomide/Bevacizumab |
Primary outcome
Primary Outcome Measures: one-year survival rate
Time frame: one year
1 secondary outcome
Secondary Outcome Measures: response rate and safety profile
Time frame: one year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Apr 2012.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jose Lutzky, MD principal investigator
Mt Sinai Medical Center
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Temozolomide and Bevacizumab in people with Melanoma, run by Mt. Sinai Medical Center, Miami at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Apr 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Primary Outcome Measures: one-year survival rate (time frame: one year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Apr 2012.