Clinical Trials

The James Cancer Center Columbus, OH

open for enrollment

Personalized Dose of Axitinib in Treating Patients with Previously Treated Local Recurrent or Metastatic Kidney Cancer

Protocol: OSU-15228

Full Title

A Phase II Study Of The Efficacy And Safety Of Axitinib Given On An Individualized Schedule For Metastatic Renal Cell Cancer After Treatment With PD-1 Or PD-L1 Inhibitors

Purpose

This phase II trial studies how well personalized dose of axitinib works in treating patients with previously treated kidney cancer that has come back after a period of improvement (recurrent) or has spread to other places in the body (metastatic). Axitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and may also prevent the growth of new blood vessels that tumors need to grow. Doctors want to know whether adjusting the standard dose of axitinib to a higher dose based on the patient response and side effects may be more effective in treating patients with previously treated metastatic kidney cancer.

Study Objective

PRIMARY OBJECTIVES:

I. To determine whether axitinib given on an individualized dose/schedule for metastatic renal cell carcinoma following immunotherapy with programmed cell death protein 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors leads to improved progression-free survival (PFS).

SECONDARY OBJECTIVES:

I. To characterize the objective response rates in patients given axitinib on an individualized dose/schedule.

II. To evaluate the tolerability and safety of an alternative method of axitinib titration.

III. To characterize the anti-tumor effect, as measured by change in tumor burden per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, of axitinib titration performed after initial RECIST progressive disease (PD) on axitinib.

OUTLINE:

Patients receive titrated doses of axitinib orally (PO) twice daily (BID). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days and for 1 year.

Are you eligible?

Inclusion Criteria:

Histologically confirmed, locally recurrent or metastatic clear cell renal cell carcinoma

Has received one prior systemic therapy regimen for metastatic renal cell carcinoma (mRCC) directed against PD-1 and/or PD-L1 which must have been the most recent regimen

Prior high-dose interleukin-2 therapy is permitted in addition to anti-PD(L)1 therapy, but is not required

Prior bevacizumab or vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) is permitted either in combination with anti-PD(L)1 therapy OR as monotherapy when given PRIOR to anti-PD(L)1 therapy

Only ONE prior VEGF-based therapy (bevacizumab or VEGF TKI) is permitted

Prior treatment with combined ipilimumab and nivolumab is permitted

Prior axitinib in any setting is not permitted

Prior neoadjuvant or adjuvant therapy is permitted if disease recurrence was greater than 6 months from the last dose of therapy

Evidence of measurable disease per RECIST 1.1

Karnofsky performance status >= 70 %

Absolute neutrophil count (ANC) >= 1,000/uL

Platelets >= 100,000/uL

Hemoglobin >= 9.0 g/dL

Serum calcium =< 12.0 mg/dL

Serum creatinine =< 1.5 x upper limit of normal (ULN)

Total serum bilirubin =< 1.5 x ULN

Serum glutamic oxaloacetic transaminase (SGOT) =< 2.5 x ULN and serum glutamate pyruvate transaminase (SGPT) =< 2.5 x ULN

Signed informed consent and willingness/ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures

Exclusion Criteria:

More than 1 VEGF-based systemic therapy, given either as monotherapy or in combination with anti-PD(L)1 therapy

Non clear cell renal cell carcinoma (RCC)

Major surgery within 4 weeks of starting the study treatment

Radiation therapy within 2 weeks of starting the study treatment; prior palliative radiotherapy to metastatic lesion(s) is permitted, provided there is at least one measurable lesion that has not been irradiated

National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 grade 3 hemorrhage within 4 weeks of starting the study treatment

Any of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack

Ongoing cardiac dysrhythmias of NCI CTCAE version 4.03 grade >= 2; controlled atrial fibrillation is permitted

Prolonged corrected QT (QTc) interval on baseline electrocardiogram (EKG) (> 450 msec for males or > 470 msec for females)

Uncontrolled hypertension (> 160/100 mm Hg despite optimal medical therapy)

Concurrent treatment on another clinical trial; supportive care trials or non-treatment trials, e.g. quality of life (QOL), and imaging trials, are allowed

Pregnancy or breastfeeding; female subjects must be surgically sterile or be postmenopausal, or must agree to use effective contraception during the period of therapy; all female subjects with reproductive potential must have a negative pregnancy test (serum) prior to enrollment; male subjects must be surgically sterile or must agree to use effective contraception during the period of therapy; the definition of effective contraception will be based on the judgment of the principal investigator or a designated associate

Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the subject inappropriate for entry into this study

Uncontrolled central nervous system (CNS) metastases; patients are considered to have controlled CNS metastases (and thus eligible) if they have completed local therapy (radiotherapy [XRT] and/or surgery) and are off steroids with clinical and radiographic stability 3 months from the end of CNS-directed therapy

Genitourinary Cancers Kidney Cancer