Axitinib before Surgery in Treating Participants with Localized Clear Cell Kidney Cancer

Status: Active

Description

This phase II trial studies how well axitinib works before surgery in treating participants with clear cell kidney cancer that has not spread to other parts of the body. Axitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving axitinib before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

Eligibility Criteria

Inclusion Criteria

  • Localized clear cell renal carcinoma without evidence of distant metastases
  • Imperative indication for nephron sparing surgery * Baseline chronic kidney disease (CKD) (stage 3, glomerular filtration rate [GFR] < 60 ml/min/1.73m^2), or anatomically or functional solitary kidney (defined by renal scintigraphy of contralateral renal unit with < 15% function) or bilateral synchronous disease; and * Radius Exophytic/endophytic properties, Nearness of the tumor to the collecting system or sinus, Anterior/posterior, and Location relative to polar lines (RENAL) score >= 10 or proximity to renal hilum (defined as < 2 mm away from at least 2 renal hilar vessels-the main artery/vein or first order branches); and * Radical nephrectomy would lead to severe CKD (stage 3b, GFR < 45 ml/min/1.73m^2)
  • 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 glutamic pyruvic 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

  • Presence of metastatic disease on radiographic imaging
  • Elective indication for nephron sparing surgery
  • Non-clear cell histology
  • Prior systemic treatment of any kind or radiotherapy for RCC
  • National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grade 3 hemorrhage within 4 weeks of starting the study treatment
  • Ongoing cardiac dysrhythmias of NCI CTCAE Version 5.0 grade >= 2. Controlled atrial fibrillation is permitted. Prolonged corrected QT interval by the Fridericia correction formula (QTcF) on screening electrocardiagraphy (EKG) > 480 msec
  • 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 hypertension (HTN): systolic blood pressure >= 150 or diastolic blood pressure >= 100 mmHg or both despite appropriate therapy
  • HTN with need for greater than three anti-hypertensive agents at baseline. Drug formulations containing two or more anti-hypertensive agents will be counted based on the number of active agents in each formulation
  • New York Heart Association (NYHA) class III or greater congestive heart failure (CHF)
  • Uncontrolled hyper- or hypothyroidism
  • Subjects with arterial thrombotic events in the prior 12 months (axitinib has never been studied in this population)
  • Subjects who have had venous thrombotic events in the prior 6 months (axitinib has never been studied in this population)

Locations & Contacts

California

San Diego
University of California San Diego
Status: Active
Contact: Ithaar H. Derweesh
Phone: 858-822-6352
Email: iderweesh@ucsd.edu

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To prospectively assess utility of axitinib in facilitation of partial nephrectomy where partial nephrectomy was not thought to be safe/possible in the setting of imperative indication for complex renal masses in renal cell cancer.

SECONDARY OBJECTIVES:

I. To determine the safety, tumor diameter (per Response Evaluation Criteria in Solid Tumors [RECIST] version [v] 1.1) volume change, surgical morbidity and renal functional outcomes following neoadjuvant axitinib for renal cell carcinoma (RCC).

OUTLINE:

Participants receive axitinib orally (PO) twice daily (BID) for 8-10 weeks in the absence of disease progression or unacceptable toxicity. Participants then undergo partial or radical nephrectomy.

After completion of study treatment, participants are followed up for 30 days.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
University of California San Diego

Principal Investigator
Ithaar H. Derweesh

Trial IDs

Primary ID 161197
Secondary IDs NCI-2018-00837
Clinicaltrials.gov ID NCT03438708