Study of the Anti-Angiogenesis Agent Axitinib in Patients With Stage III Malignant Melanoma

This study is currently recruiting participants.
Verified June 2013 by University of California, Irvine
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Chao Family Comprehensive Cancer Center, University of California, Irvine
ClinicalTrials.gov Identifier:
NCT01321437
First received: March 21, 2011
Last updated: June 19, 2013
Last verified: June 2013

March 21, 2011
June 19, 2013
December 2011
December 2017   (final data collection date for primary outcome measure)
To determine progression-free survival (PFS) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
The primary objective of this study is to determine the activity of AG-013736 in metastatic melanoma as measured by the overall response rate, complete response (CR) and partial response (PR) by RECIST. A response will also be considered to have occurred if there is a >/= 30% reduction in the involved nodal basin specific uptake value (SUV) on PET/CT.
Same as current
Complete list of historical versions of study NCT01321437 on ClinicalTrials.gov Archive Site
Determine the response rate according to RECIST criteria, safety profile of AG-013736, duration of response, and overall survival. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

The secondary objectives include the following:

  • determine the safety profile of AG-013736
  • determine the progression-free survival
  • determine overall survival
  • obtain blood samples for population pharmacokinetic analyses
  • explore relationships between clinical response and plasma soluble proteins
  • explore relationships between clinical response with host and tumor genomics
Same as current
Not Provided
Not Provided
 
Study of the Anti-Angiogenesis Agent Axitinib in Patients With Stage III Malignant Melanoma
Phase 2 Study of the Anti-Angiogenesis Agent Axitinib (AG-013736) in Patients With Stage III Malignant Melanoma

The purpose of this research study is to determine the efficacy of Axitinib in treating individuals with Stage III melanoma.

The American Cancer Society estimates that there will be about 68,720 new cases of melanoma (29,900 in men and 25,200 in women) annually in the United States, and about 8,650 people will die from this cancer. The systemic therapy of advanced disease remains palliative until new agents are found that might improve the survival of patients with stage III melanoma. However, because large-scale clinical trials are often necessary to demonstrate the safety and effectiveness of a drug, it is desirable to determine if new agents provide some measure of effectiveness of these new agents prior to investing in such studies.

Melanomas are often vascular, and a decrease in the number of blood vessels that supply the tumor may starve it of needed nutrients. An approach to blocking the growth of blood vessels that supply the tumor is to inhibit the vascular endothelial growth factor receptor tyrosine kinase (VEGFR TK) signaling pathway. Axitinib (AG 013736) is a VEGFR TK inhibitor. Besides having the potential to block the growth of blood vessels (angiogenesis) through VEGFR TK inhibition, Axitinib also has the additional antitumor potential through platelet derived growth factor receptor (PDGFR) TK inhibition.

Because of the poor prognosis of patients with stage III melanoma and indications that anti-angiogenesis compounds might have clinically meaningful activity in this disease, a Phase 2 trial of the vascular endothelial growth factor receptor tyrosine kinase (VEGFR TK) inhibitor Axitinib (AG 013736) is warranted to determine its activity and tolerability for Stage III melanoma. As a Phase 2 open label study of Axitinib, each consented patient who meets all inclusion criteria will initially receive 5 mg orally twice daily. Study tests, procedures and monitoring will be performed throughout the study to determine therapy response rate and patient safety.

Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Melanoma
  • Malignant Melanoma
Drug: Axitinib

Axitinib will be administered 5 mg orally twice each day (BID) continuously. Dose adjustments will be based on adverse events.

Eighteen patients will be entered into the first stage of a 2-stage Simon Minimax design. If there is ≥ 1 response, 14 additional patients will be entered. Up to 28 additional patients (for a total of up to 60) may be treated in order to gain additional safety and activity information should the initial 2-stage trial be positive at the end of Stage 2. Multiple centers will be used to accrue patients in a 12-month period.

Other Name: AG-013736
Experimental: Axitinib

Axitinib will be administered 5 mg orally twice each day (BID) continuously. Dose adjustments will be based on adverse events.

Eighteen patients will be entered into the first stage of a 2-stage Simon Minimax design. If there is ≥ 1 response, 14 additional patients will be entered. Up to 28 additional patients (for a total of up to 60) may be treated in order to gain additional safety and activity information should the initial 2-stage trial be positive at the end of Stage 2. Multiple centers will be used to accrue patients in a 12-month period.

Intervention: Drug: Axitinib
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
60
December 2017
December 2017   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Histologically documented melanoma with local lymph node stage III metastases.
  • No prior systemic therapy. Prior adjuvant therapy with interferon does not count.
  • No expectation of further effects of prior anticancer therapy.
  • At least 1 target lesion, as defined by RECIST (Appendix C), that has not been irradiated. New lesions that have developed in a previously irradiated field may be used as sites of measurable disease assuming all other criteria are met. All target lesions must have a unidimensional diameter of at least 1 cm for spiral CT scans if the reconstruction algorithm is 0.5 cm), or an SUV value ≥ 2.5. Baseline measurements/evaluations must be completed within 4 weeks prior to treatment.
  • Adequate bone marrow, hepatic, and renal function documented within 14 days prior to treatment as documented by:

    • absolute neutrophil count (ANC, calculated as the absolute number of neutrophils and bands) ≥1.5 x 109 cells/L
    • platelets ≥100 x 109 cells /L
    • AST and ALT ≤2.5 x upper limit of normal (ULN), unless there are liver metastases in which case AST and ALT ≤5.0 x ULN
    • total bilirubin ≤1.5 x ULN
    • serum creatinine ≤1.5 x ULN or calculated creatinine clearance ≥60 mL/min
    • urinary protein <2+ by urine dipstick. If dipstick is ≥2+ then a 24-hour urine collection can be done and the patient may enter only if urinary protein is <2 g per 24 hours
  • Age ≥18 years.
  • ECOG performance status of 0 or 1
  • 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, and the baseline diastolic blood pressure readings must be ≤90. Patients whose hypertension is controlled by antihypertensive therapies are eligible.
  • Women of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to treatment.
  • Written and voluntary informed consent

Exclusion Criteria:

  • Stage IV disease
  • History of hemoptysis
  • Gastrointestinal abnormalities including:

    • inability to take oral medication
    • requirement for intravenous alimentation
    • prior surgical procedures affecting absorption including gastric resection
    • 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 3 months without evidence of resolution documented by endoscopy or colonoscopy.
    • malabsorption syndromes.
  • Previous treatment with anti-angiogenesis agents including thalidomide, or inhibitors of epidermoid growth factor (EGF), platelet derived growth factor (PDGF), or fibroblast growth factors (FGF) receptors.
  • Current use or anticipated inability to avoid use of drugs that are known potent CYP3A4 inhibitors (ie, grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole, erythromycin, clarithromycin, ergot derivatives, indinavir, saquinavir, ritonavir, nelfinavir, lopinavir, and delavirdine).
  • Current use or anticipated inability to avoid use of drugs that are known CYP3A4 or CYP1A2 inducers (ie, carbamazepine, dexamethasone, felbamate, omeprazole, phenobarbital, phenytoin, primidone, rifabutin, rifampin, and St. John's wort).
  • Active seizure disorder or evidence of brain metastases. (Appropriate imaging should be done to rule out brain metastases.)
  • A serious uncontrolled medical disorder or active infection that would impair their ability to receive study treatment.
  • History of a malignancy (other than melanoma) except those treated with curative intent for skin cancer (other than melanoma) or in situ breast or cervical cancer or those treated with curative intent for any other cancer with no evidence of disease for 5 years.
  • 10. Major surgical procedure or any radiation therapy within 4 weeks of treatment, minimum rest period is 28 days post surgery; maximum rest period 56 days post surgery.
  • Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of this protocol.
  • Patients (male and female) having procreative potential who are not using adequate contraception or practicing abstinence.
  • Women who are pregnant or breast-feeding.
Both
18 Years and older
No
Contact: Chao Family Comprehensive Cancer Center University of California, Irvine Medical Center 1-877-UC-STUDY ucstudy@uci.edu
United States
 
NCT01321437
UCI 10-55, 2011-8282, WS830279
Yes
Chao Family Comprehensive Cancer Center, University of California, Irvine
University of California, Irvine
Pfizer
Principal Investigator: John P. Fruehauf, MD, PhD Chao Family Comprehensive Cancer Center
University of California, Irvine
June 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP