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Optimizing Pazopanib Exposure in RCC Patients (OPERA)

Primary Purpose

Locally Advanced Renal Cell Carcinoma, Metastatic Renal Cell Carcinoma

Status
Terminated
Phase
Phase 2
Locations
Germany
Study Type
Interventional
Intervention
Pazopanib
Sponsored by
Interessenverband zur Qualitätssicherung der Arbeit niedergelassener Uro-Onkologen in Deutschland e.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Locally Advanced Renal Cell Carcinoma focused on measuring RCC

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • signature of informed consent
  • age ≥ 18 years
  • histologically confirmed renal cell carcinoma with clear cell component and either locally progressed or metastasized
  • ECOG ≤ 2
  • No previous systemic therapy for locally progressed or metastasized renal cell carcinoma (previous adjuvant or neo-adjuvant therapy is permitted)
  • Adequate organ function
  • Female patients with child-bearing potential with negative serum pregnancy test within 2 weeks prior to first dose of study medication and adequate contraception
  • Lactating females

Exclusion Criteria:

  • Clinically suspected and known metastases of the central nervous system or carcinomatous meningitis except in asymptomatic patients with previously treated CNS-metastases and no necessity of steroids or anti-epileptic medication ≥ 6 months prior to start of the study medication
  • Clinically significant gastrointestinal conditions with risk of increase of gastrointestinal bleeding due to (but not limited to)
  • active peptic ulceration
  • known intraluminal metastases with risk of bleeding
  • chronic-inflammatory intestinal disease (like Morbus Crohn, ulcerative colitis) or another gastrointestinal disease with increased risk of perforation
  • abdominal fistulas in anamnesis
  • Clinically significant gastrointestinal conditions which can influence absorption of the IMP, among others (but not limited to)
  • malabsorption syndrome
  • resection of stomach or small bowel
  • Current uncontrolled infection
  • QTc corrected for heart frequency according to the Bazett formula
  • One or more of the following cardiovascular diseases within the last 6 months in the anamnesis:
  • cardiac angioplasty or coronary stent implantation
  • myocardial infarction
  • instable angina pectoris
  • coronary-arterial bypass surgery
  • symptomatic peripheral arterial occlusive disease
  • Heart failure NYHA III or IV
  • Poorly controlled high blood pressure
  • Cerebrovascular disease, including transitory ischemic attacks, pulmonary artery embolism or untreated deep vein thrombosis within 6 months of study inclusion
  • Previous major surgery or traumas within 28 days prior to start if study treatment or non-healing wound, fracture or ulcer
  • Clinical signs of active bleeding or bleeding diathesis
  • Known endobronchial lesions or lesions infiltrating the large lung arteries
  • Haemoptyses of > 2.5 mL within 8 weeks prior to first intake of study medication
  • Any other severe and/or instable medical or psychiatric pre-existing or other condition influencing patient safety, consent capacity or compliance within the study
  • Incapacity or rejection to stop not allowed medication prior to first intake of study drug and pause for the duration of the trial
  • Treatment with one of the following anti-tumour therapies:
  • Radiation or tumour embolism within 14 days before first intake of study drug
  • Chemotherapy, Immunotherapy, biological therapy, study medication or hormonal therapy within 14 days or 5 half-lives of the respective substance (whichever is longer) before first intake of the study drug. Neo-adjuvant or adjuvant therapy must have been completed for at least 6 months.
  • Any present toxicity > CTC 1° from prior anti-tumour therapy and/or toxicities worsening in severity except alopecia

Sites / Locations

  • Gesundheitszentrum Holzminden
  • Private Practice Kamann
  • Private Practice Geiges

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Normal plasma level patients and low plasma level patients.

Arm Description

Patients with normal Pazopanib plasma trough levels; "normal plasma level patients" (NPLP). Patients with low Pazopanib plasma trough levels, "low plasma level patients" (LPLP).

Outcomes

Primary Outcome Measures

Determine if in patients with a Pazopanib plasma trough level of ≤ 20 μg/mL a plasma trough level of > 20 ≤g/mL can be achieved by dose escalation.

Secondary Outcome Measures

Comparison of tumor response of patients with normal and low Pazopanib plasma trough levels.
Comparison of patients with normal Pazopanib plasma trough levels ("normal plasma level patients; NPLP) with patients with low Pazopanib plasma trough levels ("Low plasma level patients"; LPLP) with regard to the therapeutic result.
Objective remission rate.
Progression free survival.
Overall survival.
Comparison of LPLP in whom the plasma trough level could be optimized successfully and LPLP in whom the plasma trough level could not be optimized with regard to above parameters.
Correlation of plasma trough levels and side effects, especially high blood pressure.
Correlation of the occurrence of high blood pressure with oncological result (response rate).
Recording of demographic data, compliance, concomitant medication, and correlation with plasma trough levels (LPLP / NPLP).
Examination of life quality.

Full Information

First Posted
March 3, 2014
Last Updated
August 15, 2017
Sponsor
Interessenverband zur Qualitätssicherung der Arbeit niedergelassener Uro-Onkologen in Deutschland e.
Collaborators
OnkoDataMed GmbH
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1. Study Identification

Unique Protocol Identification Number
NCT02089802
Brief Title
Optimizing Pazopanib Exposure in RCC Patients
Acronym
OPERA
Official Title
Optimizing Pazopanib Exposure in RCC Patients Through Therapeutic Drug Monitoring Followed by Intrapatient Dose Escalation
Study Type
Interventional

2. Study Status

Record Verification Date
August 2017
Overall Recruitment Status
Terminated
Why Stopped
Early termination due to lack of recruitment
Study Start Date
February 25, 2014 (Actual)
Primary Completion Date
March 22, 2016 (Actual)
Study Completion Date
March 22, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Interessenverband zur Qualitätssicherung der Arbeit niedergelassener Uro-Onkologen in Deutschland e.
Collaborators
OnkoDataMed GmbH

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
Optimization of Pazopanib Exposition in Patients with Renal Cell Carcinoma by Therapeutic Drug Monitoring followed by Individual Dose Escalation.
Detailed Description
This is an open, multi-center, intraindividual dose-optimization study. Patients with locally advanced or metastatic renal cell carcinoma receive 800 mg Pazopanib daily. After 14 days the Pazopanib plasma concentration is determined. In patients who show good tolerability and plasma trough levels of ≤ 20 µg/mLthe daily dose is increased in 200 mg steps until plasma trough levels of > 20 µg/mL are achieved or dose-limiting toxicities occur, a daily dose of 1600 mg is reached, or there is disease progression. After each dose optimization the plasma concentration is determined after 14 days (day 11-15). If indicated, dose optimization is performed 21 days after the previous dose optimization (on day 18-24).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Locally Advanced Renal Cell Carcinoma, Metastatic Renal Cell Carcinoma
Keywords
RCC

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
6 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Normal plasma level patients and low plasma level patients.
Arm Type
Experimental
Arm Description
Patients with normal Pazopanib plasma trough levels; "normal plasma level patients" (NPLP). Patients with low Pazopanib plasma trough levels, "low plasma level patients" (LPLP).
Intervention Type
Drug
Intervention Name(s)
Pazopanib
Primary Outcome Measure Information:
Title
Determine if in patients with a Pazopanib plasma trough level of ≤ 20 μg/mL a plasma trough level of > 20 ≤g/mL can be achieved by dose escalation.
Time Frame
14 days after each dose optimization.
Secondary Outcome Measure Information:
Title
Comparison of tumor response of patients with normal and low Pazopanib plasma trough levels.
Description
Comparison of patients with normal Pazopanib plasma trough levels ("normal plasma level patients; NPLP) with patients with low Pazopanib plasma trough levels ("Low plasma level patients"; LPLP) with regard to the therapeutic result.
Time Frame
Up to 28 days after last dose.
Title
Objective remission rate.
Time Frame
Up to 28 days after last dose.
Title
Progression free survival.
Time Frame
Up to 28 days after last dose.
Title
Overall survival.
Time Frame
Up to 28 days after last dose.
Title
Comparison of LPLP in whom the plasma trough level could be optimized successfully and LPLP in whom the plasma trough level could not be optimized with regard to above parameters.
Time Frame
Up to 28 days after last dose.
Title
Correlation of plasma trough levels and side effects, especially high blood pressure.
Time Frame
Up to 28 days after last dose.
Title
Correlation of the occurrence of high blood pressure with oncological result (response rate).
Time Frame
Up to 28 days after last dose.
Title
Recording of demographic data, compliance, concomitant medication, and correlation with plasma trough levels (LPLP / NPLP).
Time Frame
Up to 28 days after last dose.
Title
Examination of life quality.
Time Frame
Up to 28 days after last dose.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: signature of informed consent age ≥ 18 years histologically confirmed renal cell carcinoma with clear cell component and either locally progressed or metastasized ECOG ≤ 2 No previous systemic therapy for locally progressed or metastasized renal cell carcinoma (previous adjuvant or neo-adjuvant therapy is permitted) Adequate organ function Female patients with child-bearing potential with negative serum pregnancy test within 2 weeks prior to first dose of study medication and adequate contraception Lactating females Exclusion Criteria: Clinically suspected and known metastases of the central nervous system or carcinomatous meningitis except in asymptomatic patients with previously treated CNS-metastases and no necessity of steroids or anti-epileptic medication ≥ 6 months prior to start of the study medication Clinically significant gastrointestinal conditions with risk of increase of gastrointestinal bleeding due to (but not limited to) active peptic ulceration known intraluminal metastases with risk of bleeding chronic-inflammatory intestinal disease (like Morbus Crohn, ulcerative colitis) or another gastrointestinal disease with increased risk of perforation abdominal fistulas in anamnesis Clinically significant gastrointestinal conditions which can influence absorption of the IMP, among others (but not limited to) malabsorption syndrome resection of stomach or small bowel Current uncontrolled infection QTc corrected for heart frequency according to the Bazett formula One or more of the following cardiovascular diseases within the last 6 months in the anamnesis: cardiac angioplasty or coronary stent implantation myocardial infarction instable angina pectoris coronary-arterial bypass surgery symptomatic peripheral arterial occlusive disease Heart failure NYHA III or IV Poorly controlled high blood pressure Cerebrovascular disease, including transitory ischemic attacks, pulmonary artery embolism or untreated deep vein thrombosis within 6 months of study inclusion Previous major surgery or traumas within 28 days prior to start if study treatment or non-healing wound, fracture or ulcer Clinical signs of active bleeding or bleeding diathesis Known endobronchial lesions or lesions infiltrating the large lung arteries Haemoptyses of > 2.5 mL within 8 weeks prior to first intake of study medication Any other severe and/or instable medical or psychiatric pre-existing or other condition influencing patient safety, consent capacity or compliance within the study Incapacity or rejection to stop not allowed medication prior to first intake of study drug and pause for the duration of the trial Treatment with one of the following anti-tumour therapies: Radiation or tumour embolism within 14 days before first intake of study drug Chemotherapy, Immunotherapy, biological therapy, study medication or hormonal therapy within 14 days or 5 half-lives of the respective substance (whichever is longer) before first intake of the study drug. Neo-adjuvant or adjuvant therapy must have been completed for at least 6 months. Any present toxicity > CTC 1° from prior anti-tumour therapy and/or toxicities worsening in severity except alopecia
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Goetz Geiges, MD
Organizational Affiliation
IQUO
Official's Role
Principal Investigator
Facility Information:
Facility Name
Gesundheitszentrum Holzminden
City
Holzminden
State/Province
Niedersachsen
ZIP/Postal Code
37603
Country
Germany
Facility Name
Private Practice Kamann
City
Leipzig
State/Province
Sachsen
ZIP/Postal Code
04357
Country
Germany
Facility Name
Private Practice Geiges
City
Berlin
ZIP/Postal Code
10719
Country
Germany

12. IPD Sharing Statement

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Optimizing Pazopanib Exposure in RCC Patients

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