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Study Summary
No. 2010-0451:.......Melanoma......Sapna P. Patel......Melanoma Medical Oncology
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Study Summary Title
Study Summary
Number:
2010-0451
Study Title:Phase II Study of IMC-A12 in Metastatic Uveal Melanoma
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Physician New Patient Referral
Name:Sapna P. PatelPatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:Melanoma Medical OncologyReferring MD
Call:
800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-792-2921
Contact us about clinical trials
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General Information
Disease Group:MelanomaSupported By:Imclone
Phase of Study:Phase IIReturn
Visit:
Treatment
Agents:
IMC-A12Home Care:
Treatment Loc:Both at MDACC & and Other Sites
Estimated
Length of Stay
in Houston:
Description/
Intervention:
The goal of this clinical research study is to learn if IMC-A12 (cixutumumab)
can help control metastatic uveal melanoma. Researchers will study how
cixutumumab affects the levels of tumor markers, chemicals in the blood and
tissue related to the growth and spread of cancer cells. Researchers will
study the effects of the study drug, good and/or bad, on the insulin-like
growth factor-1 receptor (IGF-1R), a natural protein in the body that may be
related to metastatic uveal melanoma. The safety of cixutumumab will also be
studied.
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Study Objectives / Outcomes
    Primary Objectives:
          1. To determine the response rate of metastatic uveal melanoma when treated with IMC-A12.
          2. To determine the safety and tolerability of IMC-A12 in patients with metastatic uveal melanoma.
    Secondary Objectives
          1. To determine the disease control rate of patients treated with IMC-A12.
          2. To determine the duration of response of patients treated with IMC-A12.
3. To determine the progression-free survival and overall survival of patients treated with
IMC-A12.
    Exploratory Objectives
1. To correlate the presence of GNAQ and GNA11 mutations with response to IMC-A12.
2. To correlate the expression of IGF-1R with response to IMC-A12.
3. To determine the effect of IMC-A12 on expression of proteins involved in initiation,
growth, and spread of uveal melanoma cells.
4. To determine resistance mechanisms to IMC-A12.
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    Study Status Information
    Study Activation / Registration Date:
    IRB Review and Approval Date:08/02/2011
    Study Type:Phase Ii Or Phase I/Ii
    Recruitment Status:Closed
    Projected Accrual:32
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    Enrollment Eligibility
    If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

    Inclusion Criteria:1) Patients must have a history of uveal melanoma and documented metastatic disease.

    2) 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.

    3) 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.

    4) 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.

    5) At least 4 weeks (28 days) since prior radiotherapy and prior adjuvant chemotherapy.

    6) Patients must have ECOG performance status of 0 - 2.

    7) Patients must be >/= 17 years of age or older. Because no dosing or adverse event data are currently available on the use IMC-A12 in patients <17 years of age, children are excluded from this study but will be eligible for future pediatric single-agent trials, if applicable.

    8) Patients must have a life expectancy of at least 3 months.

    9) Patients must have normal organ and marrow function as: leukocytes > 3,000/mm3, absolute neutrophil count >= 1,500/mm3, hemoglobin >= 9.0 g/dL, platelets >= 100,000/mm3, AST(SGOT)/ALT(SGPT) <= 3 X institutional upper limit of normal (ULN); <= 5 X institutional ULN if liver metastases present, total bilirubin < 1.5 X institutional ULN, creatinine < 1.5 X 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.

    10) Patients must have no angina at rest.

    11) 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.

    12) Both men and women and members of all races and ethnic groups are eligible for this trial.

    13) 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.

    14) Patients must have 15-20 slides of metastatic tissue for enrollment. This may take the form of archived tissue or fresh tissue biopsy.

    Exclusion Criteria:1) Patients whose site of primary melanoma is not uveal.

    2) 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 prostate or cervix or other cancers treated for cure and with a disease-free survival longer than 2 years.

    3) Patients with symptomatic central nervous system metastasis including those with CNS metastasis who require oral steroids.

    4) 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.

    5) Patients with current active infections requiring anti-infectious treatment (e.g., antibiotics, antivirals, or antifungals).

    6) Patients with a fasting blood glucose > 120 mg/dL

    7) Patients with unstable or serious concurrent medical conditions are excluded. Examples include, but are not limited to, uncontrolled ventricular arrhythmia other than PVCs, 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.

    8) Patients with one or more of the following as the only manifestations of disease are ineligible: leptomeningeal disease, ascites, pleural/pericardial effusions, carcinomatous lymphangitis CNS metastases, lesions in a previously irradiated area that have not shown definite progression, or disease only inferred from laboratory tests or markers.

    9) Patients with Gilbert's Syndrome

    10) Patients must not have had major surgery within the past 14 days.

    11) 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.

    12) HIV-positive patients with an absolute CD4 count < 300 K/uL.

    13) Patients may not be receiving any other investigational agents.

    14) Patients with a history of treatment with other agents targeting the insulin-like growth factor pathway.

    15) Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to IMC-A12.

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    Links
    Registration Number: NCT01413191
    Study Information on Clinical Trials Registry (clinicaltrials.gov)

    Other Links:
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    Results


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