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Trial record 2 of 58 for:    "Clear Cell Renal Cell Carcinoma" | "Protein Kinase Inhibitors"

Prior Axitinib as a Determinant of Outcome of Renal Surgery (PADRES)

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ClinicalTrials.gov Identifier: NCT03438708
Recruitment Status : Recruiting
First Posted : February 20, 2018
Last Update Posted : September 20, 2018
Sponsor:
Collaborator:
The Cleveland Clinic
Information provided by (Responsible Party):
Ithaar H Derweesh, MD, University of California, San Diego

Tracking Information
First Submitted Date  ICMJE January 19, 2018
First Posted Date  ICMJE February 20, 2018
Last Update Posted Date September 20, 2018
Actual Study Start Date  ICMJE March 5, 2018
Estimated Primary Completion Date October 29, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 16, 2018)
  • Percent reduction of longest diameter of tumor in millimeters [ Time Frame: 90 days ]
  • Objective Tumor Response Rate (by RECIST criteria) [ Time Frame: 90 days ]
    Percentage of patients achieving partial response (reduction in tumor diameter by at least 30% of maximum diameter) as defined by RECIST criteria
  • Effect on tumor morphometry, as measured by RENAL score [(R)adius, (E)xophytic/endophytic components, (N)earness to the collecting system or sinus, (A)neterior/posterior, and (L)ocation relative to polar lines] [ Time Frame: 90 days ]
    The RENAL nephrometry score quantifies tumor size and location relative to the major blood vessel and collecting system supply of the kidney according to 5 domains (tumor radius, exophytic/endophytic appearance, proximity to urinary collecting system, anterior/posterior location, and location with respect to renal poles). Four of these domains have a score of 1-3, with 3 indicating a more complex score within the domain. The total score is the sum of all of the domains (total minimum score being 4 and the maximum score being 12, and with more complex tumors having a higher score). The study will record effect of the medication on tumor complexity as measured by total RENAL nephrometry score.
  • Feasibility of partial nephrectomy surgery [ Time Frame: 90 days ]
    Percentage of Successful partial nephrectomy perfomed (as opposed to radical nephrectomy) with negative surgical margins determined by pathological assessment of resection margins.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03438708 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Prior Axitinib as a Determinant of Outcome of Renal Surgery
Official Title  ICMJE "PADRES" (Prior Axitinib as a Determinant of Outcome of REnal Surgery)
Brief Summary

This is a single arm phase II study of axitinib in patients with clear cell renal cell carcinoma (RCC) with strong indications for partial nephrectomy (PN) for whom PN is not currently possible due to anatomic considerations and residual renal function concerns. Evaluation of tumor downsizing will be performed including changes of tumor complexity by nephrometry score. A total of 50 participants will be enrolled.

It is hypothesized that pretreatment with axitinib will be safe and improve the feasibility of complex nephron sparing surgery in select patients with localized clear cell RCC and imperative indications for partial nephrectomy.

Detailed Description

The primary objective of the study is 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: To determine the safety, tumor diameter (per RECIST v1.1) volume change, surgical morbidity and renal functional outcomes following neoadjuvant axitinib for RCC.

Anatomical/morphometric:

  1. tumor diameter/volume change,
  2. conversion of hilar to non-hilar tumors,
  3. reduction in RENAL morphometric score.

Functional Considerations:

  1. Requirement of acute dialysis
  2. Change in Glomerular Filtration Rate (GFR)
  3. Whether or not GFR crosses 30 threshold, or decline by GFR to >50% of baseline.

Safety indices:

  1. Incidence of Clavien >3 complications
  2. Avoidance of need for multiple blood transfusions
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Clear Cell Renal Cell Carcinoma
Intervention  ICMJE Drug: Axitinib Oral Tablet [Inlyta]
Axitinib 5 milligrams (mg) administered orally (po) twice daily (BID) for 8 weeks (with titration to 7 mg BID as tolerated at 4 weeks)
Other Name: Inlyta
Study Arms  ICMJE Experimental: Axitinib Oral Tablet [Inlyta]
Axitinib 5 mg PO BID for 8-10 weeks
Intervention: Drug: Axitinib Oral Tablet [Inlyta]
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 16, 2018)
50
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 1, 2020
Estimated Primary Completion Date October 29, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Localized clear cell renal carcinoma without evidence of distant metastases
  2. Imperative indication for nephron sparing surgery

    • Baseline chronic kidney disease (CKD) (stage 3, GFR <60 ml/min/1.73m2), or anatomically or functional solitary kidney (defined by renal scintigraphy of contralateral renal unit with <15% function) or bilateral synchronous disease); and
    • 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/1.73m2).
  3. Male or female, age ≥ 18 years
  4. Karnofsky performance status ≥ 70.
  5. 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 ≤1.5 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
  6. Signed informed consent and willingness/ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures

Exclusion Criteria:

  1. Presence of metastatic disease on radiographic imaging.
  2. Elective indication for nephron sparing surgery
  3. Non-clear cell histology
  4. Prior systemic treatment of any kind or radiotherapy for RCC
  5. NCI CTCAE Version 5.0 grade 3 hemorrhage within 4 weeks of starting the study treatment
  6. 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 EKG >480 msec.
  7. 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.
  8. 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.
  9. Uncontrolled hypertension (HTN): systolic blood pressure ≥150 or diastolic blood pressure ≥ 100 mmHg or both despite appropriate therapy.
  10. 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.
  11. New York Heart Association (NYHA) class III or greater congestive heart failure (CHF)
  12. Uncontrolled hyper- or hypothyroidism.
  13. Subjects with arterial thrombotic events in the prior 12 months (axitinib has never been studied in this population)
  14. Subjects who have had venous thrombotic events in the prior 6 months (axitinib has never been studied in this population)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Candace Winkler, MS 8588225398 cmwinkler@ucsd.edu
Contact: William Brocklehurst 8585345751 wbrocklehurst@ucsd.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03438708
Other Study ID Numbers  ICMJE 161197
WI209751 ( Other Grant/Funding Number: Pfizer Inc )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Ithaar H Derweesh, MD, University of California, San Diego
Study Sponsor  ICMJE University of California, San Diego
Collaborators  ICMJE The Cleveland Clinic
Investigators  ICMJE
Study Chair: Ithaar H Derweesh, MD UC San Diego Moores Cancer Center
Principal Investigator: Ithaar H Derweesh, MD UC San Diego Moores Cancer Center
Principal Investigator: Brian I Rini, MD The Cleveland Clinic
Principal Investigator: Steven C Campbell, MD, PhD The Cleveland Clinic
PRS Account University of California, San Diego
Verification Date May 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP