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Predictive Markers of Response in a Phase II Trial of Axitinib in Advanced Melanoma

Phase 2
18 Years
Open (Enrolling)
Recurrent Melanoma, Stage IIIA Melanoma, Stage IIIB Melanoma, Stage IIIC Melanoma, Stage IV Melanoma

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Trial Information

Predictive Markers of Response in a Phase II Trial of Axitinib in Advanced Melanoma


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.

Inclusion Criteria:

Histologically or cytologically proven melanoma that is advanced (metastatic) or
unresectable Measurable disease No more than one prior regimen (0-1) of chemotherapy or
immunotherapy for metastatic or recurrent disease; therapy (chemotherapy, immunotherapy 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 3A4
(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 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 ischernic 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

Type of Study:


Study Design:

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

Outcome Measure:

Overall response rate (complete response + partial response) to axitinib as assessed using RECIST version 1.1

Outcome Time Frame:

1 year

Safety Issue:


Principal Investigator

Nikhil Khushalani

Investigator Role:

Principal Investigator

Investigator Affiliation:

Roswell Park Cancer Institute


United States: Food and Drug Administration

Study ID:

I 197811



Start Date:

December 2011

Completion Date:

Related Keywords:

  • Recurrent Melanoma
  • Stage IIIA Melanoma
  • Stage IIIB Melanoma
  • Stage IIIC Melanoma
  • Stage IV Melanoma
  • Melanoma



Roswell Park Cancer Institute Buffalo, New York  14263