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

September 19, 2018 updated by: Ithaar H Derweesh, MD, University of California, San Diego

"PADRES" (Prior Axitinib as a Determinant of Outcome of REnal Surgery)

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Anticipated)

50

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • California
      • La Jolla, California, United States, 92093
        • Recruiting
        • UC San Diego Moores Cancer Center
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / 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 Names:
  • Inlyta

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percent reduction of longest diameter of tumor in millimeters
Time Frame: 90 days
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
90 days
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.
90 days
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.
90 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of California, San Diego

Collaborators

The Cleveland Clinic

Investigators

  • 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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 5, 2018

Primary Completion (Anticipated)

October 29, 2019

Study Completion (Anticipated)

February 1, 2020

Study Registration Dates

First Submitted

January 19, 2018

First Submitted That Met QC Criteria

February 16, 2018

First Posted (Actual)

February 20, 2018

Study Record Updates

Last Update Posted (Actual)

September 20, 2018

Last Update Submitted That Met QC Criteria

September 19, 2018

Last Verified

May 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 161197
  • WI209751 (Other Grant/Funding Number: Pfizer Inc)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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