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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

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.


Condition or disease Intervention/treatment Phase
Clear Cell Renal Cell Carcinoma Drug: Axitinib Oral Tablet [Inlyta] Phase 2

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: "PADRES" (Prior Axitinib as a Determinant of Outcome of REnal Surgery)
Actual Study Start Date : March 5, 2018
Estimated Primary Completion Date : October 29, 2019
Estimated Study Completion Date : February 1, 2020


Arm Intervention/treatment
Experimental: Axitinib Oral Tablet [Inlyta]
Axitinib 5 mg PO BID for 8-10 weeks
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




Primary Outcome Measures :
  1. Percent reduction of longest diameter of tumor in millimeters [ Time Frame: 90 days ]
  2. 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

  3. 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.

  4. 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.



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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:

  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)

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): NCT03438708


Contacts
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Contact: Candace Winkler, MS 8588225398 cmwinkler@ucsd.edu
Contact: William Brocklehurst 8585345751 wbrocklehurst@ucsd.edu

Locations
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United States, California
UC San Diego Moores Cancer Center Recruiting
La Jolla, California, United States, 92093
Contact: Candace M Winkler, MS    858-822-5398    cmwinkler@ucsd.edu   
Contact: Arlene Araneta    8588226187    aaraneta@ucsd.edu   
Sponsors and Collaborators
University of California, San Diego
The Cleveland Clinic
Investigators
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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
  Study Documents (Full-Text)

Documents provided by Ithaar H Derweesh, MD, University of California, San Diego:
Study Protocol  [PDF] May 31, 2017


Publications:

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Responsible Party: Ithaar H Derweesh, MD, Professor of Urology and Radiology, University of California, San Diego
ClinicalTrials.gov Identifier: NCT03438708     History of Changes
Other Study ID Numbers: 161197
WI209751 ( Other Grant/Funding Number: Pfizer Inc )
First Posted: February 20, 2018    Key Record Dates
Last Update Posted: September 20, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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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 Ithaar H Derweesh, MD, University of California, San Diego:
Renal Cell Carcinoma
Axitinib
Nephrectomy
Neoadjuvant
Clear Cell Renal Carcinoma
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
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