Axitinib in Treating Patients With Melanoma That is Metastatic or Cannot Be Removed By Surgery

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Roswell Park Cancer Institute
Sponsor:
Collaborators:
National Comprehensive Cancer Network
Pfizer
Information provided by (Responsible Party):
Roswell Park Cancer Institute
ClinicalTrials.gov Identifier:
NCT01533948
First received: January 18, 2012
Last updated: April 14, 2014
Last verified: April 2014
  Purpose

This phase II trial studies how well axitinib works in treating patients with melanoma that is metastatic 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 Intervention Phase
Recurrent Melanoma
Stage IIIA Melanoma
Stage IIIB Melanoma
Stage IIIC Melanoma
Stage IV Melanoma
Drug: axitinib
Other: laboratory biomarker analysis
Other: pharmacogenomic studies
Other: 3'-deoxy-3'-[18F]fluorothymidine
Procedure: positron emission tomography
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Predictive Markers of Response in a Phase II Trial of Axitinib in Advanced Melanoma

Resource links provided by NLM:


Further study details as provided by Roswell Park Cancer Institute:

Primary Outcome Measures:
  • Overall response rate (complete response + partial response) to axitinib as assessed using RECIST version 1.1 [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Toxicity of axitinib as a single agent as assessed by the severity of adverse effects by NCI CTCAE version 4 [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]
  • Progression-free survival [ Time Frame: From the date of study enrollment to the first observation of progressive disease or death, assessed up to 1 year ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: From the date of study enrollment to the time of death from any cause, assessed up to 1 year ] [ Designated as safety issue: No ]
  • Change in response as a function of standardized uptake value (SUV) readings and circulative tumor cells (CTC) by FLT-PET [ Time Frame: Baseline and 4 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: December 2011
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (enzyme inhibitor)
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
Other: pharmacogenomic studies
Correlative studies
Other Name: Pharmacogenomic Study
Other: 3'-deoxy-3'-[18F]fluorothymidine
Correlative studies
Other Name: 18F-FLT
Procedure: positron emission tomography
Correlative studies
Other Names:
  • FDG-PET
  • PET
  • PET scan
  • tomography, emission computed

Detailed Description:

PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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.

TERTIARY OBJECTIVES:

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.

OUTLINE:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01533948

Locations
United States, New York
Roswell Park Cancer Institute Recruiting
Buffalo, New York, United States, 14263
Contact: Roswell Park    877-275-7724    AskRPCI@roswellpark.org   
Principal Investigator: Nikhil I. Khushalani         
Sponsors and Collaborators
Roswell Park Cancer Institute
National Comprehensive Cancer Network
Pfizer
Investigators
Principal Investigator: Nikhil Khushalani Roswell Park Cancer Institute
  More Information

No publications provided

Responsible Party: Roswell Park Cancer Institute
ClinicalTrials.gov Identifier: NCT01533948     History of Changes
Other Study ID Numbers: I 197811, NCI-2011-03037
Study First Received: January 18, 2012
Last Updated: April 14, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Melanoma
Nevi and Melanomas
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Axitinib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 26, 2014