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Study of Efficacy, Safety, and Quality of Life of Pazopanib in Patients With Advanced and/or Metastatic Renal Cell Carcinoma After Prior Checkpoint Inhibitor Treatment (IO-PAZ)

Primary Purpose

Advanced Renal Cell Carcinoma, Metastatic Renal Cell Carcinoma

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Pazopanib
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced Renal Cell Carcinoma focused on measuring renal cell carcinoma, metastatic renal cell, pazopanib, checkpoint inhibitor therapy, RCC, hypernephroma, renal adenocarcinoma, kidney cancer, renal cancer, adult

Eligibility Criteria

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

Inclusion Criteria:

  • Patient is ≥ 18 years old at the time of informed consent.
  • Patient has histologically confirmed locally recurrent or metastatic predominantly clear cell renal cell carcinoma.
  • Patient must have measurable disease based on RECIST 1.1 criteria
  • Patient must have received prior systemic therapy with an immune checkpoint inhibitor (monotherapy or combination) as 1st or 2nd line RCC treatment. Note: patients with prior mTOR inhibitor or TKI treatment as monotherapy or in combination with immune checkpoint inhibitor are allowed; however, treatment with immune checkpoint inhibitor (monotherapy or in combination) must have been the last treatment prior to study entry.
  • Last dose of immune checkpoint inhibitor therapy must have been received 4 or more weeks before start of study treatment
  • Patient must have a Karnofsky performance status ≥70%.
  • Patient must have potassium, sodium, calcium and magnesium within normal limits of the central laboratory

Exclusion Criteria:

  • Renal cell carcinoma without any clear (conventional) cell component
  • History or evidence of central nervous system (CNS) metastases (patients with pretreated metastases are eligible under certain conditions)
  • Prior treatment with pazopanib
  • Prior treatment with bevacizumab that was not given in combination with immune checkpoint inhibitor therapy.
  • Prior treatment with more than 2 lines of therapy (combination treatments are considered 1 line of therapy)
  • Patient has not recovered from toxicity from prior immune checkpoint inhibitor therapy. Recovery is defined as ≤ NCI-CTCAE Grade 1, except for liver function test levels which must be <Grade 1.
  • Disease recurrence less than 6 months from the last dose of prior neoadjuvant or adjuvant therapy (including VEGF-R TKI)
  • Patients receiving prohibited concomitant medications that cannot be discontinued or replaced by safe alternative medication at least 5 half-lives of the concomitant medication or 7 days, whichever is longer, prior to the start of pazopanib treatment.
  • Administration of any investigational drug within 4 weeks prior to the first dose of study treatment

Sites / Locations

  • Roswell Park Cancer Institute
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Pazopanib- 2nd line treatment

Pazopanib- 3rd line treatment

Arm Description

Participants received pazopanib as 2nd line treatment

Participants received pazopanib as 3rd line treatment

Outcomes

Primary Outcome Measures

Progression Free Survival (PFS)
PFS is defined as the time from the start date of pazopanib treatment to the date of the first documented progression or death due to any cause. PFS was assessed via local review according to RECIST 1.1. PFS was censored at the date of the last adequate tumor assessment if no PFS event (disease progression or death due to any cause) was observed prior to the analysis cut-off date. The PFS distribution was estimated using the Kaplan-Meier method.

Secondary Outcome Measures

Overall Response Rate (ORR) Based on Local Investigator Assessment According to RECIST v1.1
ORR is defined as the percentage of participants with best overall response of confirmed complete response (CR) or partial response (PR) based on local investigator's assessment according to RECIST v1.1. The 95% confidence intervals (CIs) were computed using Clopper and Pearson method. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Clinical Benefit Rate (CBR) Based on Local Investigator Assessment According to RECIST v1.1.
CBR is defined as the percentage of participants with a best overall response of CR or PR or an overall lesion response of stable disease (SD) or Non-CR/Non-PD lasting ≥ 24 weeks based on local investigator's assessment according to RECIST v1.1. The 95% confidence intervals (CIs) were computed using Clopper and Pearson method. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease.
Overall Survival (OS)
OS is defined as the time from the first administration of study treatment until death due to any cause. If a participant was not known to have died, survival was censored at the date of last known date patient alive. The OS distribution was estimated using the Kaplan-Meier method.
Duration of Response (DOR) Based on Local Investigators Assessment According to RECIST v1.1
DOR is defined as the time from the date of first documented response (confirmed CR or PR according to RECIST v1.1 based on local Investigators review of tumor assessment data) to the date of tumor progression, or death due to underlying cancer, whichever comes first. If a patient not had an event, duration was censored at the date of last adequate tumor assessment. The DOR distribution was calculated using the Kaplan-Meier method.
Change From Baseline in Functional Assessment of Cancer Therapy- Kidney Symptom (FKSI-DRS) Score
FKSI-DRS is a 9-item questionnaire specifically designed to evaluate symptoms that are directly attributable to kidney cancer and includes patient's symptoms in the past seven days such as lack of energy, pain, bone-pain, shortness of breath, fatigue, blood in urine, etc. Each item is scored on a 5-point scale (0=not at all to 4=very much). FKSI-DRS total score ranged from 0 (no symptoms) to 36 (most severe symptoms) with a higher score indicating greater presence of kidney cancer symptoms. The baseline is defined as the last FKSI-DRS assessment on or prior to first day of treatment. A negative change from baseline indicates improvement in kidney cancer symptom status.
Change From Baseline in EuroQoL 5-level Instrument Visual Analogue Scale (EQ-5L-5D VAS) Score
EQ-5D-5L is a standardized participant completed questionnaire that measures health-related quality of life and translates that score into an index value or utility score. EQ-5D-5L consists of two components: a health state profile and an optional visual analogue scale (VAS). The EQ-5L-5D VAS records the respondent's self-rated health on a vertical VAS, ranging from 0 (worst imaginable health state) to 100 (best imaginable health state), with higher scores indicating higher health-related quality of life. The baseline is defined as the last EQ-5L-5D assessment on or prior to first day of treatment. A positive change from baseline indicates improvement in the heath state.

Full Information

First Posted
June 20, 2017
Last Updated
August 16, 2023
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT03200717
Brief Title
Study of Efficacy, Safety, and Quality of Life of Pazopanib in Patients With Advanced and/or Metastatic Renal Cell Carcinoma After Prior Checkpoint Inhibitor Treatment
Acronym
IO-PAZ
Official Title
A Prospective International Multicenter Phase II Study to Evaluate the Efficacy, Safety and Quality of Life of Pazopanib in Patients With Advanced and/or Metastatic Renal Cell Carcinoma After Previous Therapy With Checkpoint Inhibitor Treatment
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Completed
Study Start Date
November 14, 2017 (Actual)
Primary Completion Date
August 10, 2021 (Actual)
Study Completion Date
August 10, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The main purpose of this study was to assess the progression-free survival (PFS) based on local investigator assessment of pazopanib in participants with advanced and/or metastatic renal cell carcinoma (mRCC) following prior treatment with immune checkpoint inhibitors (ICI).
Detailed Description
This was a multi-center, open-label, single-arm Phase II study to determine the efficacy, tolerability, safety and quality of life of treatment with pazopanib in subjects with advanced and/or metastatic renal cell carcinoma (RCC) following prior treatment with immune checkpoint inhibitors (ICI). Subjects could have received prior systemic therapy with an ICI (monotherapy or combination) as 1st or 2nd line RCC treatment. However, they must not have received pazopanib previously. In this study, pazopanib could be administered in the 2nd or 3rd line setting. The therapeutic line for individual subjects was assigned at the time of screening. Subjects received 800 mg of pazopanib daily until disease progression, unacceptable toxicity, death, pregnancy, start of a new anti-neoplastic therapy, discontinuation at the discretion of the investigator or patient, lost to follow-up or end of study, whichever came first.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Renal Cell Carcinoma, Metastatic Renal Cell Carcinoma
Keywords
renal cell carcinoma, metastatic renal cell, pazopanib, checkpoint inhibitor therapy, RCC, hypernephroma, renal adenocarcinoma, kidney cancer, renal cancer, adult

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
Pazopanib- 2nd line treatment
Arm Type
Experimental
Arm Description
Participants received pazopanib as 2nd line treatment
Arm Title
Pazopanib- 3rd line treatment
Arm Type
Experimental
Arm Description
Participants received pazopanib as 3rd line treatment
Intervention Type
Drug
Intervention Name(s)
Pazopanib
Intervention Description
Participants received 800mg of pazopanib once daily orally. Pazopanib was supplied as aqueous film-coated tablets containing 200 mg or 400 mg.
Primary Outcome Measure Information:
Title
Progression Free Survival (PFS)
Description
PFS is defined as the time from the start date of pazopanib treatment to the date of the first documented progression or death due to any cause. PFS was assessed via local review according to RECIST 1.1. PFS was censored at the date of the last adequate tumor assessment if no PFS event (disease progression or death due to any cause) was observed prior to the analysis cut-off date. The PFS distribution was estimated using the Kaplan-Meier method.
Time Frame
Date of first treatment to date of progression or death up to approximately 38 months
Secondary Outcome Measure Information:
Title
Overall Response Rate (ORR) Based on Local Investigator Assessment According to RECIST v1.1
Description
ORR is defined as the percentage of participants with best overall response of confirmed complete response (CR) or partial response (PR) based on local investigator's assessment according to RECIST v1.1. The 95% confidence intervals (CIs) were computed using Clopper and Pearson method. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Time Frame
Up to approximately 38 months
Title
Clinical Benefit Rate (CBR) Based on Local Investigator Assessment According to RECIST v1.1.
Description
CBR is defined as the percentage of participants with a best overall response of CR or PR or an overall lesion response of stable disease (SD) or Non-CR/Non-PD lasting ≥ 24 weeks based on local investigator's assessment according to RECIST v1.1. The 95% confidence intervals (CIs) were computed using Clopper and Pearson method. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease.
Time Frame
Up to approximately 38 months
Title
Overall Survival (OS)
Description
OS is defined as the time from the first administration of study treatment until death due to any cause. If a participant was not known to have died, survival was censored at the date of last known date patient alive. The OS distribution was estimated using the Kaplan-Meier method.
Time Frame
From date of first treatment to date of death, up to approximately 44 months
Title
Duration of Response (DOR) Based on Local Investigators Assessment According to RECIST v1.1
Description
DOR is defined as the time from the date of first documented response (confirmed CR or PR according to RECIST v1.1 based on local Investigators review of tumor assessment data) to the date of tumor progression, or death due to underlying cancer, whichever comes first. If a patient not had an event, duration was censored at the date of last adequate tumor assessment. The DOR distribution was calculated using the Kaplan-Meier method.
Time Frame
From the date of first documented response (confirmed CR or PR) to the date of tumor progression, up to approximately 36 months
Title
Change From Baseline in Functional Assessment of Cancer Therapy- Kidney Symptom (FKSI-DRS) Score
Description
FKSI-DRS is a 9-item questionnaire specifically designed to evaluate symptoms that are directly attributable to kidney cancer and includes patient's symptoms in the past seven days such as lack of energy, pain, bone-pain, shortness of breath, fatigue, blood in urine, etc. Each item is scored on a 5-point scale (0=not at all to 4=very much). FKSI-DRS total score ranged from 0 (no symptoms) to 36 (most severe symptoms) with a higher score indicating greater presence of kidney cancer symptoms. The baseline is defined as the last FKSI-DRS assessment on or prior to first day of treatment. A negative change from baseline indicates improvement in kidney cancer symptom status.
Time Frame
Baseline, Day 1 of Cycle 2, 3, 4, 5, 6, 7, 9, 11, 13, 16 and every 3rd cycle thereafter until end of treatment, and end of treatment, assessed up to approximately 38 months. Cycle=28 days
Title
Change From Baseline in EuroQoL 5-level Instrument Visual Analogue Scale (EQ-5L-5D VAS) Score
Description
EQ-5D-5L is a standardized participant completed questionnaire that measures health-related quality of life and translates that score into an index value or utility score. EQ-5D-5L consists of two components: a health state profile and an optional visual analogue scale (VAS). The EQ-5L-5D VAS records the respondent's self-rated health on a vertical VAS, ranging from 0 (worst imaginable health state) to 100 (best imaginable health state), with higher scores indicating higher health-related quality of life. The baseline is defined as the last EQ-5L-5D assessment on or prior to first day of treatment. A positive change from baseline indicates improvement in the heath state.
Time Frame
Baseline, Day 1 of Cycle 2, 3, 4, 5, 6, 7, 9, 11, 13, 16 and every 3rd cycle thereafter until end of treatment, and end of treatment, assessed up to approximately 38 months. Cycle=28 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria: Histologically confirmed locally recurrent or metastatic predominantly clear cell renal cell carcinoma. Measurable disease based on RECIST 1.1 criteria Prior systemic therapy with an immune checkpoint inhibitor (monotherapy or combination) as 1st or 2nd line RCC treatment. Note: patients with prior mTOR inhibitor or TKI treatment as monotherapy or in combination with immune checkpoint inhibitor were allowed; however, treatment with immune checkpoint inhibitor (monotherapy or in combination) must have been the last treatment prior to study entry. Last dose of immune checkpoint inhibitor therapy received 4 or more weeks before start of study treatment Karnofsky performance status ≥70%. Potassium, sodium, calcium and magnesium within normal limits of the central laboratory Key Exclusion Criteria: Renal cell carcinoma without any clear (conventional) cell component History or evidence of central nervous system (CNS) metastases (patients with pretreated metastases were eligible under certain conditions) Prior treatment with pazopanib Prior treatment with bevacizumab that was not given in combination with immune checkpoint inhibitor therapy. Prior treatment with more than 2 lines of therapy (combination treatments were considered 1 line of therapy) Not recovered from toxicity from prior immune checkpoint inhibitor therapy. Recovery was defined as ≤ NCI-CTCAE Grade 1, except for liver function test levels which must be <Grade 1. Disease recurrence less than 6 months from the last dose of prior neoadjuvant or adjuvant therapy (including VEGF-R TKI) Patients receiving prohibited concomitant medications that could not be discontinued or replaced by safe alternative medication at least 5 half-lives of the concomitant medication or 7 days, whichever was longer, prior to the start of pazopanib treatment. Administration of any investigational drug within 4 weeks prior to the first dose of study treatment
Facility Information:
Facility Name
Roswell Park Cancer Institute
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263
Country
United States
Facility Name
Novartis Investigative Site
City
Caba
State/Province
Buenos Aires
ZIP/Postal Code
C1280AEB
Country
Argentina
Facility Name
Novartis Investigative Site
City
Graz
ZIP/Postal Code
8036
Country
Austria
Facility Name
Novartis Investigative Site
City
Salzburg
ZIP/Postal Code
5020
Country
Austria
Facility Name
Novartis Investigative Site
City
Wien
ZIP/Postal Code
A-1090
Country
Austria
Facility Name
Novartis Investigative Site
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 4N2
Country
Canada
Facility Name
Novartis Investigative Site
City
Temuco
State/Province
Araucania
ZIP/Postal Code
4810469
Country
Chile
Facility Name
Novartis Investigative Site
City
Santiago
ZIP/Postal Code
8420383
Country
Chile
Facility Name
Novartis Investigative Site
City
Brno
State/Province
Czech Republic
ZIP/Postal Code
656 53
Country
Czechia
Facility Name
Novartis Investigative Site
City
Olomouc
State/Province
CZE
ZIP/Postal Code
775 20
Country
Czechia
Facility Name
Novartis Investigative Site
City
Paris
ZIP/Postal Code
75015
Country
France
Facility Name
Novartis Investigative Site
City
Strasbourg Cedex
ZIP/Postal Code
F 67098
Country
France
Facility Name
Novartis Investigative Site
City
Valenciennes
ZIP/Postal Code
59300
Country
France
Facility Name
Novartis Investigative Site
City
Hannover
ZIP/Postal Code
30625
Country
Germany
Facility Name
Novartis Investigative Site
City
Jena
ZIP/Postal Code
07740
Country
Germany
Facility Name
Novartis Investigative Site
City
Tübingen
ZIP/Postal Code
72076
Country
Germany
Facility Name
Novartis Investigative Site
City
Budapest
ZIP/Postal Code
H 1122
Country
Hungary
Facility Name
Novartis Investigative Site
City
Sevilla
State/Province
Andalucia
ZIP/Postal Code
41013
Country
Spain
Facility Name
Novartis Investigative Site
City
Madrid
ZIP/Postal Code
28041
Country
Spain
Facility Name
Novartis Investigative Site
City
London
ZIP/Postal Code
NW3 2QG
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
Manchester
ZIP/Postal Code
M20 2BX
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
Preston
ZIP/Postal Code
PR2 9HT
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on https://www.clinicalstudydatarequest.com/.
Links:
URL
https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=1110
Description
A Plain Language Trial Summary is available on novctrd.com

Learn more about this trial

Study of Efficacy, Safety, and Quality of Life of Pazopanib in Patients With Advanced and/or Metastatic Renal Cell Carcinoma After Prior Checkpoint Inhibitor Treatment

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