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Phase II Study of IMC-A12 in Metastatic Uveal Melanoma

Phase 2
17 Years
Open (Enrolling)
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

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Trial Information

Phase II Study of IMC-A12 in Metastatic Uveal Melanoma


I. To determine the response rate of metastatic uveal melanoma when treated with IMC-A12

II. To determine the safety and tolerability of IMC-A12 in patients with metastatic uveal


I. 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.


I. 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.

Inclusion Criteria:

- 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

- At least 4 weeks (28 days) since prior radiotherapy and prior adjuvant

- Patients must have ECOG performance status of 0 - 2

- 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

- 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

- 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

- 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

Exclusion Criteria:

- 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 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

- 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

- 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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Response rate (i.e., the percentage of subjects with a confirmed complete or partial response)

Outcome Description:

The response rate and the adjusted 95% confidence interval will be calculated.

Outcome Time Frame:

Up to 2 years

Safety Issue:


Principal Investigator

Sapna Patel

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

August 2011

Completion Date:

Related Keywords:

  • 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
  • Melanoma
  • Uveal Neoplasms



Thomas Jefferson University Hospital Philadelphia, Pennsylvania  19131
M D Anderson Cancer Center Houston, Texas  77030