Ciliary Body and Choroid Melanoma, Medium/Large SizePhase 2NCT01413191
Cixutumumab in Treating Patients With Metastatic Melanoma of the Eye
A Phase 2 study testing Cixutumumab and Laboratory biomarker analysis in people with Ciliary Body and Choroid Melanoma, Medium/Large Size and Ciliary Body and Choroid Melanoma, Small Size, run by National Cancer Institute (NCI) at 2 sites in United States.
Trial summary
This phase II trial studies how well giving cixutumumab works in treating patients with metastatic melanoma of the eye. Monoclonal antibodies, such as cixutumumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Read more about this study
- Who is it for?
- Ages 17 years and older
- Conditions the study is for
- Ciliary Body and Choroid Melanoma, Medium/Large Size, Ciliary Body and Choroid Melanoma, Small Size, Iris Melanoma
- What is being tested?
- Cixutumumab and Laboratory biomarker analysis
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 2 sitesUnited States
- Study dates
- Aug 2011to Jun 2014
- 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 17 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients must have a history of uveal melanoma and documented metastatic disease
- Patients must have at least one unidimensionally measurable lesion; if this is a cutaneous lesion it must be at least 10 mm by caliper measure; if it is a visceral or nodal or soft tissue lesion, it must be clearly measurable > 20 mm with conventional techniques or > 10 mm with spiral CT scan; bone lesions are not considered measurable
- One prior systemic chemotherapy and any number of immunotherapies or vaccine therapies are allowed; prior treatment with hepatic arterial chemotherapy infusion or perfusion or chemoembolization of liver metastasis is allowed; prior treatment with radiation therapy is allowed but not more than 3000 cGy to fields including substantial marrow; patients are not required to have had prior therapy
- At least 6 weeks (42 days) since any prior immunotherapy, cytokine, biologic, vaccine or other therapy unless patients have progressed during therapy; if progression occurred during therapy, patient must have recovered from any side effects
- At least 4 weeks (28 days) since prior radiotherapy and prior adjuvant chemotherapy
- Patients must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2
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- Patients must have a life expectancy of at least 3 months
- Leukocytes > 3,000/mm3
- Absolute neutrophil count ≥ 1,500/mm3
- Hemoglobin ≥ 9.0 g/dL
- Platelets ≥ 100,000/mm3
- Aspartate transaminase-alanine transaminase ratio (AST(SGOT)/ALT(SGPT)) ≤ 3 times institutional upper limit of normal (ULN); ≤ 5 times institutional ULN if liver metastases present
- Total bilirubin < 1.5 times institutional ULN
- Creatinine < 1.5 times institutional ULN OR creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
- Fasting serum glucose < 120 mg/dL or < institutional ULN
- Patients must have no angina at rest
- The effects of IMC-A12 on the developing human fetus at the recommended therapeutic dose are unknown; for this reason and because monoclonal antibodies could be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation and for 3 months after the last dose of IMC-A12; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
- Both men and women and members of all races and ethnic groups are eligible for this trial
- Patients must have the ability to understand and the willingness to sign a written informed consent form indicating that they are aware of the investigational nature of this study and in keeping with the policies of the institution
Who cannot join
- Patients whose site of primary melanoma is not uveal
- Patients who have a current history of neoplasm other than the entry diagnosis except for curatively treated non-melanoma skin cancer or carcinoma in situ of the cervix or other cancers treated for cure and with a disease-free survival longer than 5 years
- Patients with symptomatic central nervous system metastasis including those with central nervous system (CNS) metastasis who require oral steroids for cerebral edema or have progression on CT/MRI
- Patients who are pregnant or nursing and patients who are not practicing an acceptable method of birth control; patients may not breast-feed while on this study; pregnant women are excluded from this study because IMC-A12 is a monoclonal antibody 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 IMC-A12, breastfeeding women are excluded
- Patients with current active infections requiring anti-infectious treatment (e.g., antibiotics, antivirals, or antifungals)
- Patients with poorly controlled diabetes mellitus; patients with a history of diabetes mellitus are allowed to participate, provided that their blood glucose is within normal range (fasting < 120 mg/dL or below institutional ULN) and that they are on a stable dietary or therapeutic regimen for this condition
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- Patients with unstable or serious concurrent medical conditions are excluded; examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, spinal cord compression, superior vena cava syndrome, or any psychiatric disorder that prohibits obtaining informed consent
- Patients with one or more of the following as the only manifestations of disease are ineligible: leptomeningeal disease, ascites, pleural/pericardial effusions, carcinomatous lymphangitis
- Patients with Gilbert's Syndrome
- Patients must not have had major surgery within the past 14 days
- Patients must not receive any concurrent chemotherapy or immunotherapy while on study; only palliative radiotherapy is permitted to symptomatic lesions in which event the irradiated lesions may not be considered target or non-target lesions for response; palliative radiation immediately before or during the study is acceptable provided there is evaluable disease that has been radiated; palliative radiation is acceptable provided that the irradiated lesions are not used to determine response assessment
- HIV-positive patients with an absolute CD4 count < 300 K/uL
- Patients may not be receiving any other investigational agents
- Patients with a history of treatment with other agents targeting the insulin-like growth factor pathway
- Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to IMC-A12
Trial locations and contacts
2 sites in 1 country.
United States2 sites
M D Anderson Cancer Center
Houston, Texas, 77030
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, 19107
About this study
Official title: Phase II Study of IMC-A12 in Metastatic Uveal Melanoma
This phase II trial studies how well giving cixutumumab works in treating patients with metastatic melanoma of the eye. Monoclonal antibodies, such as cixutumumab, 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.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the response rate of metastatic uveal melanoma when treated with IMC-A12 (cixutumumab).
II. To determine the safety and tolerability of IMC-A12 in patients with metastatic uveal melanoma.
SECONDARY OBJECTIVES:
- To determine the disease control rate of patients treated with IMC-A12. II. To determine the duration of response of patients treated with IMC-A12. III. To determine the progression-free survival and overall survival of patients treated with IMC-A12.
TERTIARY OBJECTIVES:
- To correlate the presence of GNAQ and GNA11 mutations with response to IMC-A12.
II. To correlate the expression of IGF-1R with response to IMC-A12. III. To determine the effect of IMC-A12 on expression of proteins involved in initiation, growth, and spread of uveal melanoma cells.
IV. To determine resistance mechanisms to IMC-A12.
OUTLINE: This is a multicenter study.
Patients receive cixutumumab intravenously (IV) over 1 hour on days 1 and 15. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Archived and fresh tumor tissue and serum samples may be collected for correlative studies.
After completion of study treatment, patients are followed up for 30 days and then every 3 months for 1 year.
- Conditions
- Ciliary Body and Choroid Melanoma, Medium/Large Size, Ciliary Body and Choroid Melanoma, Small Size, Iris Melanoma, Metastatic Intraocular Melanoma, Recurrent Intraocular Melanoma, Stage IV Intraocular Melanoma
- Being tested
- Cixutumumab, Laboratory biomarker analysis
- Medical subject headings
- Uveal Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CixutumumabBiological
Also called anti-IGF-1R recombinant monoclonal antibody IMC-A12, IMC-A12
10 mg/kg IV infusion over 1 hour every 2 weeks with treatment cycle defined as 4 weeks
Laboratory biomarker analysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| CixutumumabTreatment | Experimental | Cixutumumab 10 mg/kg intravenous (IV) over 1 hour on days 1 and 15 for 4 week courses. Receives: Biological: Cixutumumab; Other: Laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Response
Response rate is the percentage of subjects with a confirmed complete or partial response using revised Response Evaluation Criteria in Solid Tumors (RECIST) where changes in only the largest diameter (unidimensional measurement) of the tumor lesions are used in the RECIST criteria: Complete Response (CR): Disappearance all target lesions; pathological lymph nodes reduction in short axis to <10 mm. Partial Response (PR): 30% or > decrease in sum diameters of target lesions, reference baseline sum diameters. Progressive Disease (PD): 20% or > increase in sum diameters of target lesions, reference smallest sum on study (includes baseline sum if smallest on study); and sum must demonstrate absolute increase of 5+ mm. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, reference smallest sum diameters while on study.
Measured: Baseline to 2 years
Secondary outcomes (5)
Disease Control Rate
Disease Control Rate is the proportion of subjects with a confirmed complete or partial response of any duration or stable disease ≥3 months in duration.
Measured: Up to 2 years
Duration of Response
Duration of response will be summarized by using descriptive statistics. Median duration of response will be estimated by using the Kaplan-Meier method.
Measured: From the date criteria are first met for complete or partial response until the first date of documented progression, assessed up to 2 years
Progression-free Survival (PFS)
Measured: Up to 2 years
Overall Survival (OS)
Measured: Up to 2 years
Durable Response Rate
Durable Response Rate is the proportion of subjects with a confirmed complete or partial response ≥ 6 months in duration.
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Aug 2011 (estimated)
- Study startAug 2011
- Primary completionMar 2013
- Study completionJun 2014
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
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Sapna Patel, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01413191
- Sponsor's protocol ID
- NCI-2011-02228
- Other IDs
- NCI-2011-02228, 2010-0451, 8832, P30CA016672, N01CM00039
- Status last verified
- Feb 2020
- First submitted
- 9 Aug 2011
- Last updated
- 19 Feb 2020
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 19 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of IMC-A12 in Metastatic Uveal Melanoma
- ClinicalTrials.gov ID
- NCT01413191
- Acronym / sponsor ID
- NCI-2011-02228
- Conditions
- Ciliary Body and Choroid Melanoma, Medium/Large Size, Ciliary Body and Choroid Melanoma, Small Size, Iris Melanoma, Metastatic Intraocular Melanoma, Recurrent Intraocular Melanoma, Stage IV Intraocular Melanoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Aug 2011
- Primary completion
- Mar 2013 (actual)
- Study completion
- Jun 2014 (actual)
- First posted
- 10 Aug 2011 (estimated)
- Results
- Posted 20 Jul 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 studies how well giving cixutumumab works in treating patients with metastatic melanoma of the eye. Monoclonal antibodies, such as cixutumumab, 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.
Detailed description
PRIMARY OBJECTIVES:
- To determine the response rate of metastatic uveal melanoma when treated with IMC-A12 (cixutumumab).
II. To determine the safety and tolerability of IMC-A12 in patients with metastatic uveal melanoma.
SECONDARY OBJECTIVES:
- To determine the disease control rate of patients treated with IMC-A12. II. To determine the duration of response of patients treated with IMC-A12. III. To determine the progression-free survival and overall survival of patients treated with IMC-A12.
TERTIARY OBJECTIVES:
- To correlate the presence of GNAQ and GNA11 mutations with response to IMC-A12.
II. To correlate the expression of IGF-1R with response to IMC-A12. III. To determine the effect of IMC-A12 on expression of proteins involved in initiation, growth, and spread of uveal melanoma cells.
IV. To determine resistance mechanisms to IMC-A12.
OUTLINE: This is a multicenter study.
Patients receive cixutumumab intravenously (IV) over 1 hour on days 1 and 15. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Archived and fresh tumor tissue and serum samples may be collected for correlative studies.
After completion of study treatment, patients are followed up for 30 days and then every 3 months for 1 year.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CixutumumabTreatment | Experimental | Biological: Cixutumumab, Other: Laboratory biomarker analysisCixutumumab 10 mg/kg intravenous (IV) over 1 hour on days 1 and 15 for 4 week courses. |
Who may qualify
- Ages
- 17 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (19 listed)
- Patients must have a history of uveal melanoma and documented metastatic disease
- Patients must have at least one unidimensionally measurable lesion; if this is a cutaneous lesion it must be at least 10 mm by caliper measure; if it is a visceral or nodal or soft tissue lesion, it must be clearly measurable > 20 mm with conventional techniques or > 10 mm with spiral CT scan; bone lesions are not considered measurable
- One prior systemic chemotherapy and any number of immunotherapies or vaccine therapies are allowed; prior treatment with hepatic arterial chemotherapy infusion or perfusion or chemoembolization of liver metastasis is allowed; prior treatment with radiation therapy is allowed but not more than 3000 cGy to fields including substantial marrow; patients are not required to have had prior therapy
- Patients must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2
- Patients must have a life expectancy of at least 3 months
Key exclusion criteria (15 listed)
- Patients whose site of primary melanoma is not uveal
- Patients who have a current history of neoplasm other than the entry diagnosis except for curatively treated non-melanoma skin cancer or carcinoma in situ of the cervix or other cancers treated for cure and with a disease-free survival longer than 5 years
- Patients with symptomatic central nervous system metastasis including those with central nervous system (CNS) metastasis who require oral steroids for cerebral edema or have progression on CT/MRI
- Patients who are pregnant or nursing and patients who are not practicing an acceptable method of birth control; patients may not breast-feed while on this study; pregnant women are excluded from this study because IMC-A12 is a monoclonal antibody 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 IMC-A12, breastfeeding women are excluded
- Patients with current active infections requiring anti-infectious treatment (e.g., antibiotics, antivirals, or antifungals)
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 |
|---|---|---|
| CixutumumabAlso: anti-IGF-1R recombinant monoclonal antibody IMC-A12, IMC-A1210 mg/kg IV infusion over 1 hour every 2 weeks with treatment cycle defined as 4 weeks | Biological | CixutumumabTreatment |
| Laboratory biomarker analysisCorrelative studies | Other | CixutumumabTreatment |
Primary outcome
Number of Participants With Response
Time frame: Baseline to 2 years
Response rate is the percentage of subjects with a confirmed complete or partial response using revised Response Evaluation Criteria in Solid Tumors (RECIST) where changes in only the largest diameter (unidimensional measurement) of the tumor lesions are used in the RECIST criteria: Complete Response (CR): Disappearance all target lesions; pathological lymph nodes reduction in short axis to <10 mm. Partial Response (PR): 30% or > decrease in sum diameters of target lesions, reference baseline sum diameters. Progressive Disease (PD): 20% or > increase in sum diameters of target lesions, reference smallest sum on study (includes baseline sum if smallest on study); and sum must demonstrate absolute increase of 5+ mm. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, reference smallest sum diameters while on study.
5 secondary outcomes
Disease Control Rate
Time frame: Up to 2 years
Duration of Response
Time frame: From the date criteria are first met for complete or partial response until the first date of documented progression, assessed up to 2 years
Progression-free Survival (PFS)
Time frame: Up to 2 years
Overall Survival (OS)
Time frame: Up to 2 years
Durable Response Rate
Time frame: Up to 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Feb 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- University of Texas MD Anderson Cancer Center Official WebsiteLink provided by the sponsor.
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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.
Sapna Patel principal investigator
M.D. Anderson Cancer Center
2 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 Cixutumumab and Laboratory biomarker analysis in people with Ciliary Body and Choroid Melanoma, Medium/Large Size and Ciliary Body and Choroid Melanoma, Small Size, run by National Cancer Institute (NCI) at 2 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 19 inclusion and 15 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 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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?
Yes. Results are posted in the registry (first posted 20 Jul 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?
Number of Participants With Response (time frame: Baseline to 2 years). 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 Feb 2020.