Clinical trial NCT01413191: Cixutumumab in Treating Patients With Metastatic Melanoma of the Eye
Official title: Phase II Study of IMC-A12 in Metastatic Uveal Melanoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2011-08-10
Enrollment: 18
Sex: ALL
Minimum age (years): 17
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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. Others find tumor cells and help kill them or carry tumor-killing substances to them.

Detailed description: PRIMARY OBJECTIVES:

I. 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:

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.

TERTIARY OBJECTIVES:

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.

Eligibility criteria: 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 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
* 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

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 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
* 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

Primary outcomes:
measure: Number of Participants With Response
timeFrame: Baseline to 2 years
Secondary outcomes:
measure: Disease Control Rate
timeFrame: Up to 2 years
measure: Duration of Response
timeFrame: From the date criteria are first met for complete or partial response until the first date of documented progression, assessed up to 2 years
measure: Progression-free Survival (PFS)
timeFrame: Up to 2 years
measure: Overall Survival (OS)
timeFrame: Up to 2 years
measure: Durable Response Rate
timeFrame: Up to 2 years
Other outcomes:
measure: Tumor Shrinkage for All Efficacy-evaluable Patients
timeFrame: Up to 2 years
Locations:
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Sapna Patel
role: PRINCIPAL_INVESTIGATOR
References: