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

NCT01321437 | Completed Phase 2 Results DMC

• 4 other identifiers: UCI 10-55 [HS# 2011-8282]2011-8282WS830279NCI-2012-02173
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Melanoma; Malignant Melanoma; Stage IIIA Melanoma; Stage IIIB Melanoma; Stage IIIC Melanoma

Keywords

Melanoma; Axitinib; Anti-angiogenesis; Neoadjuvant Melanoma

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate, Defined as the Percentage of Patients With a Confirmed Clinical Response (CR) or Partial Response (PR)

  The response rate (CR or PR according to Response Evaluation Criteria in Solid Tumors (RECIST) will be provided with an exact 95% 2-sided confidence interval calculated using a method based on the F distribution.

  Up to 1 year

Secondary Outcomes (4)

• Progression-free Survival (PFS)

  From the date of first dose of axitinib to the first date that criteria for progression were met or the patient died, assessed up to 1 year

• Duration of Overall Response

  From the day the criteria for PR or CR were met to the first day criteria for progression occurred, assessed up to 1 year

• Survival

  From the day of first dose of axitinib to the day of death, until at least one year after the initial dose for the last treated patient.

• Frequencies of Patients Experiencing at Least One Adverse Event (AE)

  Up to at least 28 days after the last dose of study drug, on average of 1 year.

Study Arms (1)

Axitinib

EXPERIMENTAL

Patients receive axitinib PO BID on days 1-28. Treatment repeats every 4 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery within 14-21 days after completion of treatment. Beginning 28-56 days after surgery, patients receive axitinib PO BID on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity

Procedure: therapeutic conventional surgery; Other: laboratory biomarker analysis; Drug: Axitinib; Other: pharmacological study

Interventions

therapeutic conventional surgery PROCEDURE

Undergo surgery

Axitinib

laboratory biomarker analysis OTHER

Correlative studies

Axitinib

Axitinib DRUG

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

Also known as: AG-013736, Inlyta

Axitinib

pharmacological study OTHER

Correlative studies

Axitinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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, 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 standard uptake value (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 10\^9 cells/L
• platelets ≥100 x 10\^9 cells /L
• aspartate aminotransferase (AST) and alanine aminotransferase (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.
• Eastern Cooperative Oncology Group (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.

You may not qualify if:

• 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 cytochrome P450 3A4 (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 Cytochrome P450 1A2 (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.

Sponsors & Collaborators

• University of California, Irvine: lead
• Pfizer: collaborator

Study Sites (1)

Chao Family Comprehensive Cancer Center

Orange, California, 92868, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

Axitinib

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Indazoles; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: UC Irvine Health / Chao Family Comprehensive Cancer Center
• Organization: UC Irvine Health / Chao Family Comprehensive Cancer Center

ucstudy@uci.edu

1-877-UC-STUDY

Study Officials

• John P. Fruehauf, MD, PhD

  Chao Family Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 21, 2011
• First Posted: March 23, 2011
• Study Start: December 1, 2011
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: January 20, 2021
• Results First Posted: January 20, 2021

Record last verified: 2020-12

Locations

US (1)