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Therapeutic Drug Monitoring of Sunitinib and Pazopanib in Advanced or Metastatic Renal Cell Carcinoma (SUP-R)

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: NCT02555748
Recruitment Status : Active, not recruiting
First Posted : September 22, 2015
Last Update Posted : March 15, 2019
Sponsor:
Collaborator:
University Hospital, Bordeaux
Information provided by (Responsible Party):
Institut Claudius Regaud

Tracking Information
First Submitted Date  ICMJE September 4, 2015
First Posted Date  ICMJE September 22, 2015
Last Update Posted Date March 15, 2019
Actual Study Start Date  ICMJE November 17, 2015
Estimated Primary Completion Date June 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 21, 2015)
  • Part I: Pharmacokinetics - Pazopanib or Sunitinib plasma concentrations [ Time Frame: On day 1 and day 15 during cycle 1 and cycle 2 (cycle length is 6 weeks) ]
  • Part II: Tolerance - Proportion of patients without treatment discontinuation due to adverse event (AE) during the first year. [ Time Frame: 5.5 years ]
    This corresponds to the number of patients without treatment discontinuation due to AE among the total number of patients in each group.
  • Part II: Efficacy - Proportion of patients without progression at 1 year. This corresponds to the number of patients without progression at 1 year among the total number of patients in each group [ Time Frame: 5.5 years ]
  • Part I: Adverse Events according to NCI toxicity scale (version 4.03) [ Time Frame: 1.5 years ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 21, 2015)
  • Part I and II: Objective Response (e.g. Complete or Partial Response) [ Time Frame: 5.5 years ]
    Objective Response will be defined using RECIST Criteria version 1.1.
  • Part I and II:- Progression free survival. [ Time Frame: 5.5 years ]
    Progression free survival is defined as the time from inclusion until progression (RECIST Criteria version 1.1) or death. Patients alive at last follow-up news are censored at this date.
  • Part I and II: Safety according to the classification of the NCI: Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.03. [ Time Frame: 5.5 years ]
  • Part I and II: Hand-foot syndrome (HFS) [ Time Frame: 5.5 years ]
    Hand-foot syndrome (HFS) will be evaluated using the HFS-14 questionnaire. This scale specifically developed for patients with HFS is a valid and valuable tool for measuring HFS-related QoL impairment.
  • Part I and II: Quality of life using the quality of life questionnaire (QLQ)-C30 [ Time Frame: 5.5 years ]
    Quality of life will be evaluated using the QLQ-C30 questionnaire
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Therapeutic Drug Monitoring of Sunitinib and Pazopanib in Advanced or Metastatic Renal Cell Carcinoma
Official Title  ICMJE Therapeutic Drug Monitoring of Sunitinib and Pazopanib in Advanced or Metastatic Renal Cell Carcinoma
Brief Summary

This pilot study is an open-label interventional study, prospective, non-comparative, sequential (two stages), national, multicenter study.

Patients starting therapy with sunitinib or pazopanib as standard first line treatment for advanced or metastatic renal cell carcinoma will enter the study in one of the two cohorts (115 patients will be treated by sunitinib and 99 patients will be treated by pazopanib).

The purpose of this study is to examine the feasibility of sunitinib and pazopanib dose individualisation based on therapeutic drug monitoring (TDM) and to assess the benefit of this approach in terms of tolerance and efficacy compared with the current empirical method based only on tolerance observation.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Other
Condition  ICMJE Metastatic Renal Cell Cancer
Intervention  ICMJE
  • Drug: Pazopanib
  • Drug: Sunitinib
Study Arms  ICMJE
  • Active Comparator: Pazopanib

    The daily dose of pazopanib will be the standard dose i.e. 800 mg once a day (2 tablets of 400 mg in one oral administration per day) administered each day, continuously, during the treatment phase (complete cycle will be defined as a 6-week period).

    During the first stage of the study (Part I), adjustment of drug dose will be made according to individual patient tolerance to treatment evaluated by clinical and biological monitoring; During the second stage of the study (Part II), dose modification should also be performed according to individual patient tolerance to treatment evaluated by clinical and biological monitoring ans also by using the new Pharmacokinetic-Pharmacodynamic (PK-PD) Algorithm elaborated during the first part.

    Intervention: Drug: Pazopanib
  • Active Comparator: Sunitinib

    Sunitinib will be administered at the standard dose of 50 mg, once daily during 4 consecutive weeks, followed by a wash-out period of 2 weeks (corresponding to a complete cycle of 6 weeks).

    During the first stage of the study (Part I), dose adjustment of drug dose will be made according to individual patient tolerance to treatment evaluated by clinical and biological monitoring; During the second stage (Part II), dose modification should also be performed according to individual patient tolerance to treatment evaluated by clinical and biological monitoring ans also by using the new Pharmacokinetic-Pharmacodynamic (PK-PD) Algorithm elaborated during the first part.

    Intervention: Drug: Sunitinib
Publications * Not Provided

*   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 Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: March 14, 2019)
47
Original Estimated Enrollment  ICMJE
 (submitted: September 21, 2015)
214
Estimated Study Completion Date  ICMJE June 2021
Estimated Primary Completion Date June 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Patients starting therapy with sunitinib or pazopanib as standard first line treatment for advanced or metastatic renal cell carcinoma.
  2. Measurable tumours as defined by RECIST criteria version 1.1.
  3. Age ≥ 18 years old.
  4. WHO Performance Status ≤ 2.
  5. Life expectancy ≥ 6 months.
  6. Adequate cardiac function (baseline Left Ventricular Ejection Fraction (LVEF) ≥ 50% determined by Multiple Gated Acquisition scan (MUGA) or echocardiography) and pulmonary function.
  7. Renal function defined as creatinine clearance (Cockcroft and Gault formula) > 30 mL/min.
  8. Adequate liver function defined as: total bilirubin ≤ 1.5 x Upper Limit of Normal (ULN); Alanine AminoTansferase (ALAT) and Aspartate AminoTransferase (ASAT) ≤ 2.5 x ULN; Concomitant elevation in bilirubin and ASAT/ALAT above 1.0 x ULN is not allowed.
  9. Patients must provide written informed consent prior to performance of study-specific procedures or assessments, and must be willing to comply with treatment and follow-up.
  10. Negative pregnancy test for women in childbearing potential.
  11. Women of childbearing potential must be using an adequate method of contraception to avoid pregnancy throughout the study (before study entry and until 30 days after the last administration of study treatment).
  12. Patients affiliated to a social health insurance.

Exclusion Criteria:

  1. Patients without any venous access for blood sampling.
  2. Hypersensitivity to the active substance or to any of the excipients.
  3. History or clinical evidence of central nervous system (CNS) metastases, except for individuals who have previously-treated CNS metastases.
  4. Corrected QT interval (QTc) > 480msecs using Bazett's formula.
  5. Patients with other concurrent severe and/or uncontrolled medical disease which could compromise participation in the study, such as, but not limited to:

    • Uncontrolled infection.
    • Cardiovascular conditions within the last 6 months such as cardiac angioplasty or stenting, myocardial infarction, unstable angina, coronary artery bypass graft surgery, symptomatic peripheral vascular disease, Class III or IV congestive heart failure, as defined by the New-York Heart Association (NYHA), clinically significant irregular heartbeat requiring medication.
    • Poorly controlled hypertension [defined as systolic blood pressure of ≥140 mmHg or diastolic pressure of ≥90 mmHg).
    • History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or deep venous thrombosis (DVT) within the past 6 months.

    Note: patients with recent DVT who have been treated with therapeutic anti-coagulating agents for at least 6 weeks are eligible.

  6. Evidence of active bleeding or bleeding diathesis.
  7. Patients being treated with drugs recognized as being strong inhibitors or inducers of the isoenzyme cytochrome P450 isoenzyme 3A4 (CYP3A4) within the last 14 days prior to inclusion and/or during the study.
  8. Patients already treated with an anticancer treatment in the previous four weeks or patient requiring anticancer treatment during the study (chemotherapy, immunotherapy, hormonotherapy, radiotherapy or surgery).
  9. Pregnant or breast-feeding women.
  10. Positive diagnostic of HIV, B and C hepatitis.
  11. Patients with serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with patient's safety, provision of informed consent, or compliance to study procedures.
  12. Patients who has forfeited his/her freedom by administrative or legal award or who is under guardianship.
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 information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02555748
Other Study ID Numbers  ICMJE 14 URO 06
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Institut Claudius Regaud
Study Sponsor  ICMJE Institut Claudius Regaud
Collaborators  ICMJE University Hospital, Bordeaux
Investigators  ICMJE
Principal Investigator: Christine CHEVREAU, MD IUCT-O
PRS Account Institut Claudius Regaud
Verification Date March 2019

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