Ciliary Body and Choroid Melanoma, Medium/Large SizePhase 2NCT00450255
VEGF Trap in Treating Patients With Recurrent Stage III or Stage IV Melanoma That Cannot Be Removed by Surgery
A Phase 2 study testing ziv-aflibercept and pharmacological study in people with Ciliary Body and Choroid Melanoma, Medium/Large Size and Extraocular Extension Melanoma, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
This phase II trial is studying how well VEGF Trap works in treating patients with recurrent stage III or stage IV melanoma that cannot be removed by surgery. Combinations of biological substances in VEGF Trap may be able to carry tumor-killing substances directly to melanoma cells. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Ciliary Body and Choroid Melanoma, Medium/Large Size, Extraocular Extension Melanoma, Iris Melanoma
- What is being tested?
- ziv-aflibercept and pharmacological study
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2007to Jan 2011
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed stage III or IV melanoma
- Cutaneous, ocular, or mucosal melanoma allowed
- Recurrent, inoperable disease
- Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan
- No evidence of CNS disease, including primary brain tumor or brain metastases
- No brain metastases by MRI or CT scan within the past 4 weeks
Show all 48Show fewer
- ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
- Life expectancy > 3 months
- WBC ≥ 3,000/mm³
- Absolute neutrophil count ≥ 1,500/mm³
- Platelet count ≥ 75,000/mm³
- Bilirubin < 1.5 times upper limit of normal (ULN)
- AST and ALT ≤ 2.5 times ULN
- Creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 60 mL/min
- Urine protein:creatinine ratio < 1 OR urine protein < 500 mg by 24-hour urine collection
- PT INR ≤ 1.5 unless on full-dose warfarin
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for ≥ 6 months after completion of study treatment
- No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
- No history of allergic reactions attributed to compounds of similar chemical or biological composition to agents used in the study
- No serious or nonhealing wound, ulcer, or bone fracture
- No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
- No significant traumatic injury within the past 28 days
- No clinically significant cardiovascular disease, including any of the following:
- Cerebrovascular accident within the past 6 months
- Uncontrolled hypertension, defined as blood pressure (BP) > 150/100 mm Hg or systolic BP > 180 mm Hg if diastolic BP < 90 mm Hg within the past 3 months
- Myocardial infarction, coronary artery bypass graft, or unstable angina within the past 6 months
- New York Heart Association class III-IV congestive heart failure
- Serious cardiac arrhythmia requiring medication
- Unstable angina pectoris within the past 6 months
- Clinically significant peripheral vascular disease within the past 6 months
- Pulmonary embolism, deep vein thrombosis, or other thromboembolic event within the past 6 months
- No evidence of bleeding diathesis or coagulopathy
- No concurrent uncontrolled illness, including, but not limited to any of the following:
- Ongoing or active infection
- Psychiatric illness or social situation that would preclude study compliance
- Recovered from all prior therapy and major surgery
- No prior chemotherapy or hormonal therapy
- More than 7 days since prior core visceral organ biopsy
- More than 4 weeks since prior biologic therapy or radiotherapy
- More than 28 days since prior major surgery or open biopsy
- No concurrent major surgery
- No other concurrent investigational agents
- No concurrent combination antiretroviral therapy for HIV-positive patients
- Concurrent full-dose warfarin with PT INR > 1.5 allowed provided the following criteria are met:
- INR in range (2-3) on a stable dose of oral anticoagulant or low molecular weight heparin
- No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices)
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 2 Study Evaluating the Efficacy of VEGF Trap in Patients With Recurrent Inoperable Stage III or Stage IV Melanoma
This phase II trial is studying how well VEGF Trap works in treating patients with recurrent stage III or stage IV melanoma that cannot be removed by surgery. Combinations of biological substances in VEGF Trap may be able to carry tumor-killing substances directly to melanoma cells. It may also stop the growth of melanoma by blocking blood flow to the tumor.
Read the detailed description
PRIMARY OBJECTIVES:
- Determine the antitumor response rate (complete and partial response) in patients with recurrent inoperable stage III or IV melanoma treated with VEGF Trap.
II. Compare the progression-free survival of patients treated with this regimen vs historical controls.
SECONDARY OBJECTIVES:
- Determine the overall survival of patients treated with this regimen. II. Determine the toxicity and tolerability of this regimen in these patients. III. Determine the impact of this regimen on laboratory correlates including anti-VEGF Trap antibody testing and pharmacokinetics in these patients.
OUTLINE: This is a multicenter study.
Patients receive VEGF Trap IV over 1 hour on day 1. Treatment repeats every 14 days for at least 6 courses in the absence of disease progression or unacceptable toxicity.
Blood samples are collected at baseline, prior to course 2, and 60 days after completion of study treatment for pharmacokinetic and pharmacodynamic studies. Samples are analyzed by enzyme-linked immunosorbent assay.
After completion of study treatment, patients are followed periodically for 5 years.
- Conditions
- Ciliary Body and Choroid Melanoma, Medium/Large Size, Extraocular Extension Melanoma, Iris Melanoma, Metastatic Intraocular Melanoma, Recurrent Intraocular Melanoma, Recurrent Melanoma
- Being tested
- ziv-aflibercept, pharmacological study
- Medical subject headings
- Uveal Melanoma, Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ziv-afliberceptBiological
Also called aflibercept, vascular endothelial growth factor trap, VEGF Trap, Zaltrap
Given IV
Also called pharmacological studies
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Arm I | Experimental | Patients receive Aflibercept IV at 4 mg/kg over 1 hour on day 1. Treatment repeats every 14 days for at least 6 courses in the absence of disease progression or unacceptable toxicity. Receives: Biological: ziv-aflibercept; Other: pharmacological study |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate (CR + PR)
Using the RECIST v1.0 criteria for target lesions assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Objective Response = CR + PR.",
Measured: Start of treatment to disease progression/recurrence, up to 5 years
4 Month Progression-free Survival
Estimated using the product-limit method of Kaplan and Meier. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Measured: 4 months
Secondary outcomes (3)
Overall Survival
Will be estimated by the Kaplan-Meier method.
Measured: From the initial date of treatment to the recorded date of death, assessed up to 5 years
Number of Participants With Toxicities
The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 were utilized for AE grading and reporting. Grade 3 and higher adverse events considered possibly, probably or definitely related to aflibercept are summarized.
Measured: Up to 5 years
Impact of the VEGF Trap Therapy on Laboratory Correlates
Measured: Up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Mar 2007 (estimated)
- Study startJun 2007
- Primary completionJan 2011
- Study completionJan 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Ciliary Body and Choroid Melanoma, Medium/Large SizeStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Ahmad Tarhini, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00450255
- Sponsor's protocol ID
- NCI-2009-00182
- Other IDs
- NCI-2009-00182, PHII-77, CDR0000535719, PHII-77, 7522, N01CM62209, P30CA033572
- Status last verified
- Apr 2018
- First submitted
- 20 Mar 2007
- Last updated
- 24 May 2018
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 24 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Study Evaluating the Efficacy of VEGF Trap in Patients With Recurrent Inoperable Stage III or Stage IV Melanoma
- ClinicalTrials.gov ID
- NCT00450255
- Acronym / sponsor ID
- NCI-2009-00182
- Conditions
- Ciliary Body and Choroid Melanoma, Medium/Large Size, Extraocular Extension Melanoma, Iris Melanoma, Metastatic Intraocular Melanoma, Recurrent Intraocular Melanoma, Recurrent Melanoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 41 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Jun 2007
- Primary completion
- Jan 2011 (actual)
- Study completion
- Jan 2011 (actual)
- First posted
- 22 Mar 2007 (estimated)
- Results
- Posted 4 Feb 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II trial is studying how well VEGF Trap works in treating patients with recurrent stage III or stage IV melanoma that cannot be removed by surgery. Combinations of biological substances in VEGF Trap may be able to carry tumor-killing substances directly to melanoma cells. It may also stop the growth of melanoma by blocking blood flow to the tumor.
Detailed description
PRIMARY OBJECTIVES:
- Determine the antitumor response rate (complete and partial response) in patients with recurrent inoperable stage III or IV melanoma treated with VEGF Trap.
II. Compare the progression-free survival of patients treated with this regimen vs historical controls.
SECONDARY OBJECTIVES:
- Determine the overall survival of patients treated with this regimen. II. Determine the toxicity and tolerability of this regimen in these patients. III. Determine the impact of this regimen on laboratory correlates including anti-VEGF Trap antibody testing and pharmacokinetics in these patients.
OUTLINE: This is a multicenter study.
Patients receive VEGF Trap IV over 1 hour on day 1. Treatment repeats every 14 days for at least 6 courses in the absence of disease progression or unacceptable toxicity.
Blood samples are collected at baseline, prior to course 2, and 60 days after completion of study treatment for pharmacokinetic and pharmacodynamic studies. Samples are analyzed by enzyme-linked immunosorbent assay.
After completion of study treatment, patients are followed periodically for 5 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Arm I | Experimental | Biological: ziv-aflibercept, Other: pharmacological studyPatients receive Aflibercept IV at 4 mg/kg over 1 hour on day 1. Treatment repeats every 14 days for at least 6 courses in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (48 listed)
- Histologically confirmed stage III or IV melanoma
- Cutaneous, ocular, or mucosal melanoma allowed
- Recurrent, inoperable disease
- Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan
- No evidence of CNS disease, including primary brain tumor or brain metastases
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| ziv-afliberceptAlso: aflibercept, vascular endothelial growth factor trap, VEGF Trap, ZaltrapGiven IV | Biological | Arm I |
| pharmacological studyAlso: pharmacological studiesCorrelative studies | Other | Arm I |
Primary outcome
Objective Response Rate (CR + PR)
Time frame: Start of treatment to disease progression/recurrence, up to 5 years
Using the RECIST v1.0 criteria for target lesions assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Objective Response = CR + PR.",
4 Month Progression-free Survival
Time frame: 4 months
Estimated using the product-limit method of Kaplan and Meier. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
3 secondary outcomes
Overall Survival
Time frame: From the initial date of treatment to the recorded date of death, assessed up to 5 years
Number of Participants With Toxicities
Time frame: Up to 5 years
Impact of the VEGF Trap Therapy on Laboratory Correlates
Time frame: Up to 5 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 May 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Ahmad Tarhini principal investigator
University of Pittsburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ziv-aflibercept and pharmacological study in people with Ciliary Body and Choroid Melanoma, Medium/Large Size and Extraocular Extension Melanoma, run by National Cancer Institute (NCI) at 1 site 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 48 inclusion and 0 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 24 May 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
Yes. Results are posted in the registry (first posted 4 Feb 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Objective Response Rate (CR + PR) (time frame: Start of treatment to disease progression/recurrence, up to 5 years). The study lists 2 primary outcomes in all. 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 24 May 2018.