Clinical Trials /

Axitinib Given on an Individualized Schedule for Metastatic Renal Cell Cancer

NCT02579811

Description:

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.

Related Conditions:
  • Renal Cell Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Axitinib Given on an Individualized Schedule for Metastatic Renal Cell Cancer
  • Official 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

Clinical Trial IDs

  • ORG STUDY ID: CASE7815
  • NCT ID: NCT02579811

Conditions

  • Metastatic Renal Cell Cancer

Interventions

DrugSynonymsArms
AxitinibAxitinib

Purpose

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.

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 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.
    

Trial Arms

NameTypeDescriptionInterventions
AxitinibExperimentalAll 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.
  • Axitinib

Eligibility Criteria

        Inclusion Criteria:

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

          -  Has received one prior systemic therapy regimen for 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 VEGF 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 ULN

               -  Total serum bilirubin ≤1.5 x ULN

               -  SGOT≤2.5 x ULN and 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 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 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Median Progression-free survival
Time Frame:Up to 6-months
Safety Issue:
Description:The primary endpoint of progression-free survival will be estimated using the Kaplan-Meier method. Summary statistics will be provided along with 95% confidence intervals.

Secondary Outcome Measures

Measure:Patients with Complete Response
Time Frame:From day of screening to disease progression or death, up to 5 years
Safety Issue:
Description: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.
Measure:Patients with Partial Response
Time Frame:From day of screening to disease progression or death, up to 5 years
Safety Issue:
Description: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.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Case Comprehensive Cancer Center

Trial Keywords

  • Kidney
  • Cancer
  • Axitinib
  • Pd-1 inhibitor
  • Pd-L1 inhibitor

Last Updated

February 24, 2018