Axitinib Given on an Individualized Schedule for Metastatic Renal Cell Cancer

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

Axitinib is a drug which is approved by the FDA for patients with advanced kidney cancer who have already received some treatment. It works by reducing blood flow to a tumor. Axitinib is normally give at 5mg twice per day and sometimes this dose is increased if patients tolerate it. The purpose of this study is to figure out a different way to decide which dose of axitinib each patient should receive based on the side effects they experience.

Study Overview

• Status: Completed
• Conditions: Metastatic Renal Cell Cancer
• Intervention / Treatment: Drug: Axitinib

Detailed Description

Primary objective To determine whether axitinib given on an individualized dose/schedule for metastatic renal cell carcinoma following immunotherapy with PD-1 and PD-L1 Inhibitors leads to improved progression-free survival (PFS).

Secondary objectives:

1. To characterize the objective response rates in patients given axitinib on an individualized dose/schedule.
2. To evaluate the tolerability and safety of an alternative method of axitinib titration.
3. To characterize the anti-tumor effect, as measured by change in tumor burden per RECIST 1.1, of axitinib titration performed after initial RECIST PD on axitinib.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope Comprehensive Cancer Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt-Ingram Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Kinas 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
  • Prior treatment with combined ipilimumab and nivolumab is permitted
  • Prior axitinib in any setting is not permitted
  • A minimum of two weeks since last dose of most recent renal cell cancer therapy assuming resolution of clinically significant treatment-related toxicities to grade 1, baseline, or controlled with supportive medications
• Evidence of measurable disease per RECIST 1.1.
• Karnofsky performance status ≥ 70 %.

• Adequate organ function as defined by:

  • Absolute neutrophil count (ANC) ≥1,000/μL
  • Platelets ≥100,000/μL
  • Hemoglobin ≥9.0 g/dL
  • Serum calcium ≤12.0 mg/dL
  • Serum creatinine ≤2.0 x Upper Limit of Normal (ULN)
  • Total serum bilirubin ≤1.5 x ULN
  • SGOT≤2.5 x ULN and Serum Glutamic Pyruvic Transaminase (SGPT) ≤2.5x ULN
• Signed informed consent and willingness/ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures

Exclusion Criteria:

• 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.
• NCI 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.
• 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. 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 (XRT and/or surgery) and are off steroids with clinical and radiographic stability 3 months from the end of CNS-directed therapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Axitinib; All subjects will be given axitinib on an individualized dosing schedule. Axitinib will be administered orally beginning with 5mg twice a day and can be escalated or reduced if specific grade 2 or greater toxicity develops. Axitinib will continue until progression. At progressive disease, dose escalation above current dose is allowed based on investigator discretion of clinical benefit. However, axitinib should be discontinued if a subject experiences a second RECIST progressive disease following dose escalation, patient intolerability, or at provider discretion.

Drug: Axitinib; The intent is to maximize sustained dose intensity of axitinib based on individual tolerability using dose modification criteria

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median Progression-free Survival	The primary endpoint of progression-free survival in months (per per RECIST v1.1 criteria) will be estimated using the Kaplan-Meier method. Summary statistics will be provided along with 95% confidence intervals.	Up to 18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patients With Complete Response	Tumor Response, defined as overall confirmed objective response, is confirmed complete response (CR) according to the RECIST 1.1 criteria. RECIST 1.1: Complete response (CR) is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.	Up to 4 months of treatment and approximately 1 year of follow-up
Patients With Partial Response	Tumor Response, defined as overall confirmed objective response, is confirmed complete response (CR) according to the RECIST 1.1 criteria. RECIST 1.1: Partial response (PR) is defined as a >=30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions.	Up to 4 months of treatment and approximately 1 year of follow-up
Objective Response Rate (ORR)	ORR as defined by Recist V. 1.1. ORR = (CR + PR)	Up to 4 months of treatment and approximately 1 year of follow-up

Collaborators and Investigators

• Sponsor: Case Comprehensive Cancer Center
• Investigators: Principal Investigator: Moshe Ornstein, MD, MA, Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

Publications and helpful links

General Publications

• Ornstein MC, Pal SK, Wood LS, Tomer JM, Hobbs BP, Jia XS, Allman KD, Martin A, Olencki T, Davis NB, Gilligan TD, Mortazavi A, Rathmell WK, Garcia JA, Rini BI. Individualised axitinib regimen for patients with metastatic renal cell carcinoma after treatment with checkpoint inhibitors: a multicentre, single-arm, phase 2 study. Lancet Oncol. 2019 Oct;20(10):1386-1394. doi: 10.1016/S1470-2045(19)30513-3. Epub 2019 Aug 16.

Study record dates

Study Major Dates

• Study Start (Actual): December 30, 2015
• Primary Completion (Actual): August 21, 2019
• Study Completion (Actual): June 20, 2023

Study Registration Dates

• First Submitted: October 14, 2015
• First Submitted That Met QC Criteria: October 16, 2015
• First Posted (Estimated): October 20, 2015

Study Record Updates

• Last Update Posted (Actual): June 29, 2023
• Last Update Submitted That Met QC Criteria: June 26, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Cancer; Kidney; Axitinib; Pd-1 inhibitor; Pd-L1 inhibitor
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Carcinoma, Renal Cell; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Axitinib
• Other Study ID Numbers: CASE7815

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No