Trial record 1 of 1 for:    NCT01533948
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Axitinib in Treating Patients With Melanoma That is Metastatic or Cannot Be Removed by Surgery

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01533948
Recruitment Status : Terminated (low accrual)
First Posted : February 16, 2012
Last Update Posted : June 1, 2016
National Cancer Institute (NCI)
National Comprehensive Cancer Network
Information provided by (Responsible Party):
Roswell Park Cancer Institute

Brief Summary:
This phase II trial studies how well axitinib works in treating patients with melanoma that has spread to other places in the body or cannot be removed by surgery. Axitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Condition or disease Intervention/treatment Phase
Extraocular Extension Melanoma Metastatic Intraocular Melanoma Recurrent Intraocular Melanoma Recurrent Melanoma Stage IIIA Intraocular Melanoma Stage IIIA Melanoma Stage IIIB Intraocular Melanoma Stage IIIB Melanoma Stage IIIC Intraocular Melanoma Stage IIIC Melanoma Stage IV Intraocular Melanoma Stage IV Melanoma Drug: axitinib Other: laboratory biomarker analysis Phase 2

Detailed Description:


I. To determine the overall response rate (ORR) to axitinib in advanced melanoma. This will be assessed using the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1.


I. Evaluate toxicity of axitinib as a single agent. II. Determine progression-free survival and overall survival. III. Explore the utility of 3'-deoxy-3'-[18F] fluorothymidine-labeled positron emission tomography (FLT-PET) as a predictive marker for response and compare to standard radiographic imaging.


I. Examine the prognostic and predictive significance of circulating melanoma tumor cells.

II. To examine whether functionally relevant polymorphisms in axitinib-related genes (vascular endothelial growth factor receptor [VEGFR] 1, VEGFR2 and VEGFR3) correlate with efficacy and toxicity of axitinib in advanced melanoma.


Patients receive axitinib orally (PO) twice daily (BID). Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 25 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Predictive Markers of Response in a Phase II Trial of Axitinib in Advanced Melanoma
Study Start Date : January 2012
Actual Primary Completion Date : July 2015

Arm Intervention/treatment
Experimental: Treatment (axitinib)
Patients receive axitinib PO BID. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Drug: axitinib
Given PO
Other Names:
  • AG-013736
  • Inlyta
Other: laboratory biomarker analysis
Correlative studies

Primary Outcome Measures :
  1. Overall response rate (complete response + partial response) to axitinib as assessed using RECIST version 1.1 [ Time Frame: Up to 30 days ]
    Continuous variables will be summarized with commonly used statistics (mean, standard deviation, median, etc.), with sub-group associations tested using the Wilcoxon Rank Sum test.

Secondary Outcome Measures :
  1. Incidence of toxicity of axitinib as a single agent as assessed by the severity of adverse effects by NCI CTCAE version 4 [ Time Frame: Up to 30 days ]
    Continuous variables will be summarized with commonly used statistics (mean, standard deviation, median, etc.), with sub-group associations tested using the Wilcoxon Rank Sum test.

  2. Progression-free survival (PFS) [ Time Frame: From the date of study enrollment to the first observation of progressive disease or death, assessed up to 30 days ]
    The distribution will be described using Kaplan-Meier and proportional hazards methods.

  3. Overall survival (OS) [ Time Frame: From the date of study enrollment to the time of death from any cause, assessed up 30 days ]
    The distribution will be described using Kaplan-Meier and proportional hazards methods.

  4. Change in response as a function of standardized uptake value (SUV) readings by FLT-PET and circulative tumor cells [ Time Frame: Baseline and 4 weeks ]
    Models will be fit using logistic regression methods. Goodness of fit for these models will be assessed using the Hosmer-Lemeshow test. The predictive accuracy of the models will be described using the area under the receiver operating characteristic curve (the so-called "c" statistic). Generally, models with c >= 0.8 are considered to have good predictive ability. The association SUV measurements and OS/PFS time to event will be considered using Kaplan Meier and proportional hazards methods as discussed above.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Histologically or cytologically proven melanoma (including uveal) that is advanced (metastatic) or unresectable
  • Measurable disease
  • No more than two prior regimens (0-2) of systemic therapy for metastatic or recurrent disease; therapy (systemic or radiotherapy) administered in the neo-adjuvant or adjuvant setting for previously localized disease is permitted, provided it was completed more than 3 months prior to enrollment; palliative radiotherapy is permitted provided it is completed >= 2 weeks prior to study therapy initiation and there is at least one measurable lesion outside the radiation field; at least 2 weeks since the end of prior systemic treatment, radiotherapy, or surgical procedure with resolution of all treatment-related toxicity to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 grade =< 1 or back to baseline except for alopecia or hypothyroidism
  • Eastern Cooperative Oncology Group (ECOG) performance status of =< 2
  • Life expectancy >= 12 weeks
  • Absolute neutrophil count (ANC) >= 1500 cells/mm^3
  • Platelets >= 75,000 cells/mm^3
  • Hemoglobin >= 9.0 g/dL
  • Creatinine =< 1.5 X upper limit normal (ULN) or calculated creatinine clearance >= 60 mL/min
  • Bilirubin =< 1.5 X ULN
  • Transaminase =< 2.5 X ULN (for documented liver metastases, transaminase up to 5 X ULN is permitted)
  • Random urinary protein/creatinine ratio < 2
  • Have the ability to swallow and retain oral medication
  • No evidence of preexisting uncontrolled hypertension as documented by 2 baseline blood pressure readings taken at least 1 hour apart; the baseline systolic blood pressure readings must be =< 140 mm Hg, and the baseline diastolic blood pressure readings must be =< 90 mm Hg; patients whose hypertension is controlled by antihypertensive therapies are eligible
  • Women of childbearing potential must have a negative serum or urine pregnancy test within 3 days prior to treatment
  • Patients of child-bearing potential must agree to use acceptable contraceptive methods (e.g., double barrier) during treatment and for 6 months following completion of study treatment
  • Patient or legal representative must understand the investigational nature of this study and sign an Institutional Review Board (IRB) approved written informed consent form prior to receiving any study related procedure

Exclusion Criteria:

  • Prior anti-angiogenic therapy
  • Major surgery < 4 weeks or radiation therapy < 2 weeks of starting the study treatment; prior palliative radiotherapy to metastatic lesion(s) is permitted, provided there is at least 1 measurable lesion that has not been irradiated
  • Significant history of bleeding events (e.g., hemoptysis, grade 3 or grade 4 gross hematuria) within 6 months prior to registration
  • Presence of serious non-healing wounds, ulcers (including gastro-intestinal) and bone fractures
  • Gastrointestinal abnormalities including:

    • Inability to take oral medication
    • Requirement for intravenous alimentation
    • Prior surgical procedures affecting absorption including total gastric resection; segmental small bowel or colon resection is permitted
    • Treatment for active peptic ulcer disease in the past 6 months
    • Active gastrointestinal bleeding, unrelated to cancer, as evidenced by hematemesis, hematochezia or melena in the past 6 months without evidence of resolution documented by endoscopy or colonoscopy
    • Malabsorption syndromes
    • History of gastrointestinal (GI) perforation within prior 12 months
  • Current use or anticipated need for treatment with drugs that are known potent cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors (i.e., grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole, erythromycin, telithromycin, clarithromycin, indinavir, saquinavir, ritonavir, nelfinavir, lopinavir, atazanavir, amprenavir, fosamprenavir and delavirdine)
  • Current use or anticipated need for treatment with drugs that are known CYP3A4 or cytochrome P450, family 1, subfamily A, polypeptide 2 (CYP1A2) inducers (i.e., carbamazepine, dexamethasone, felbamate, omeprazole, phenobarbital, phenytoin, amobarbital, nevirapine, primidone, rifabutin, rifampin, and St. John's wort)
  • Requirement of therapeutic anticoagulant therapy with oral vitamin K antagonists; low-dose anticoagulants for maintenance of patency of central venous access devise or prevention of deep venous thrombosis is allowed; therapeutic use of low molecular weight heparin (or similar parenteral drug) for venous-thromboembolic disease is allowed
  • Active seizure disorder or evidence of untreated brain metastases, spinal cord compression, or carcinomatous meningitis; patients with brain metastases that have been stable for >= 4 weeks by radiographic documentation following definitive therapy will be permitted provided this is not the only site of metastatic disease
  • Arterial thrombotic events within 6 months of registration, including myocardial infarction, unstable angina or angina requiring medical or surgical intervention in the past 6 months, coronary/peripheral artery bypass graft, cerebrovascular accident, transient ischemic attack and clinically significant peripheral vascular disease (i.e., claudication on less than 1 block)
  • Current congestive heart failure (New York Heart Association [NYHA] class II, III or IV)
  • Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness
  • History of a malignancy except those treated with curative intent for skin cancer (other than melanoma), in-situ breast or in-situ cervical cancer, or those treated with curative intent for any other cancer with no evidence of disease for 3 years
  • Female patients who are pregnant or lactating
  • Received an investigational agent within 30 days prior to enrollment
  • A serious uncontrolled medical disorder or active infection that would impair their ability to receive study treatment
  • Any condition which in the investigator's opinion would prohibit the understanding or rendering of informed consent and compliance with the requirements of this protocol

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01533948

United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
Sponsors and Collaborators
Roswell Park Cancer Institute
National Cancer Institute (NCI)
National Comprehensive Cancer Network
Principal Investigator: Matuesz Opyrchal, MD Roswell Park Cancer Institute

Responsible Party: Roswell Park Cancer Institute Identifier: NCT01533948     History of Changes
Other Study ID Numbers: I 197811
NCI-2011-03037 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
I 197811 ( Other Identifier: Roswell Park Cancer Institute )
P30CA016056 ( U.S. NIH Grant/Contract )
First Posted: February 16, 2012    Key Record Dates
Last Update Posted: June 1, 2016
Last Verified: May 2016

Additional relevant MeSH terms:
Uveal Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Eye Neoplasms
Neoplasms by Site
Eye Diseases
Uveal Diseases
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action