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Axitinib Given on an Individualized Schedule for Metastatic Renal Cell Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02579811
Recruitment Status : Active, not recruiting
First Posted : October 20, 2015
Results First Posted : August 7, 2020
Last Update Posted : August 7, 2020
Sponsor:
Information provided by (Responsible Party):
Case Comprehensive Cancer Center

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Metastatic Renal Cell Cancer Drug: Axitinib Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 40 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : December 30, 2015
Actual Primary Completion Date : August 21, 2019
Estimated Study Completion Date : August 21, 2023

Resource links provided by the National Library of Medicine

Drug Information available for: Axitinib

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




Primary Outcome Measures :
  1. Median Progression-free Survival [ Time Frame: Up to 18 months ]
    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.


Secondary Outcome Measures :
  1. Patients With Complete Response [ Time Frame: Up to 4 months of treatment and approximately 1 year of follow-up ]
    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.

  2. Patients With Partial Response [ Time Frame: Up to 4 months of treatment and approximately 1 year of follow-up ]
    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.

  3. Objective Response Rate (ORR) [ Time Frame: Up to 4 months of treatment and approximately 1 year of follow-up ]
    ORR as defined by Recist V. 1.1. ORR = (CR + PR)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02579811


Locations
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United States, California
City of Hope Comprehensive Cancer Center
Duarte, California, United States, 91010
United States, Ohio
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44195
The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
Columbus, Ohio, United States, 43210
United States, Tennessee
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232
Sponsors and Collaborators
Case Comprehensive Cancer Center
Investigators
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Principal Investigator: Moshe Ornstein, MD, MA Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
  Study Documents (Full-Text)

Documents provided by Case Comprehensive Cancer Center:
Informed Consent Form  [PDF] November 26, 2018

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT02579811    
Other Study ID Numbers: CASE7815
First Posted: October 20, 2015    Key Record Dates
Results First Posted: August 7, 2020
Last Update Posted: August 7, 2020
Last Verified: August 2020

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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
Keywords provided by Case Comprehensive Cancer Center:
Kidney
Cancer
Axitinib
Pd-1 inhibitor
Pd-L1 inhibitor
Additional relevant MeSH terms:
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Carcinoma, Renal Cell
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Axitinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action