Advanced Renal Cell CarcinomaPhase 2IO-PAZNCT03200717
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
A Phase 2 study testing Pazopanib in people with Advanced Renal Cell Carcinoma and Metastatic Renal Cell Carcinoma, run by Novartis Pharmaceuticals at 22 sites in 11 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Renal Cell Carcinoma, Metastatic Renal Cell Carcinoma
- What is being tested?
- Pazopanib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 62 participants
- Where
- 22 sitesin 11 countries
- Study dates
- 14 Nov 2017to 10 Aug 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Show all 9Show fewer
- 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
Trial locations and contacts
22 sites in 11 countries.
22 sites in 11 countries
Austria3 sites
Novartis Investigative Site
Graz, 8036
Novartis Investigative Site
Salzburg, 5020
Novartis Investigative Site
Vienna, A-1090
France3 sites
Novartis Investigative Site
Paris, 75015
Novartis Investigative Site
Strasbourg, F 67098
Novartis Investigative Site
Valenciennes, 59300
Germany3 sites
Novartis Investigative Site
Hanover, 30625
Novartis Investigative Site
Jena, 07740
Novartis Investigative Site
Tübingen, 72076
United Kingdom3 sites
Novartis Investigative Site
London, NW3 2QG
Novartis Investigative Site
Manchester, M20 2BX
Novartis Investigative Site
Preston, PR2 9HT
Chile2 sites
Novartis Investigative Site
Santiago, 8420383
Novartis Investigative Site
Temuco, Araucania, 4810469
Czechia2 sites
Novartis Investigative Site
Brno, Czech Republic, 656 53
Novartis Investigative Site
Olomouc, CZE, 775 20
Spain2 sites
Novartis Investigative Site
Madrid, 28041
Novartis Investigative Site
Seville, Andalusia, 41013
United States1 site
Roswell Park Cancer Institute
Buffalo, New York, 14263
About this study
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
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).
Read the 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.
- Being tested
- Pazopanib
- Keywords
- renal cell carcinoma, metastatic renal cell, pazopanib, checkpoint inhibitor therapy, RCC, hypernephroma, renal adenocarcinoma, kidney cancer, renal cancer, adult
- Medical subject headings
- Carcinoma, Renal Cell, Kidney Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PazopanibDrug
Participants received 800mg of pazopanib once daily orally. Pazopanib was supplied as aqueous film-coated tablets containing 200 mg or 400 mg.
| Study group | Role | What they receive |
|---|---|---|
| Pazopanib- 2nd line treatment | Experimental | Participants received pazopanib as 2nd line treatment Receives: Drug: Pazopanib |
| Pazopanib- 3rd line treatment | Experimental | Participants received pazopanib as 3rd line treatment Receives: Drug: Pazopanib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Date of first treatment to date of progression or death up to approximately 38 months
Secondary outcomes (6)
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.
Measured: Up to approximately 38 months
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.
Measured: Up to approximately 38 months
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.
Measured: From date of first treatment to date of death, up to approximately 44 months
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.
Measured: From the date of first documented response (confirmed CR or PR) to the date of tumor progression, up to approximately 36 months
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.
Measured: 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
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.
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2017
- Study start14 Nov 2017
- Primary completion10 Aug 2021
- Study completion10 Aug 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Advanced Renal Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 62 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03200717
- Sponsor's protocol ID
- CPZP034A2410
- Other IDs
- 2017-000708-10, 2017
- Acronym
- IO-PAZ
- Status last verified
- Aug 2023
- First submitted
- 20 Jun 2017
- Last updated
- 21 Aug 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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/.
Study at a glance
From the registry record, last updated by the sponsor on 21 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03200717
- Acronym / sponsor ID
- IO-PAZ / CPZP034A2410
- Keywords
- renal cell carcinoma, metastatic renal cell, pazopanib, checkpoint inhibitor therapy, RCC, hypernephroma, renal adenocarcinoma, kidney cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 62 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 14 Nov 2017 (actual)
- Primary completion
- 10 Aug 2021 (actual)
- Study completion
- 10 Aug 2021 (actual)
- First posted
- 27 Jun 2017 (actual)
- Results
- Posted 21 Mar 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pazopanib- 2nd line treatment | Experimental | Drug: PazopanibParticipants received pazopanib as 2nd line treatment |
| Pazopanib- 3rd line treatment | Experimental | Drug: PazopanibParticipants received pazopanib as 3rd line treatment |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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%.
Key exclusion criteria (9 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PazopanibParticipants received 800mg of pazopanib once daily orally. Pazopanib was supplied as aqueous film-coated tablets containing 200 mg or 400 mg. | Drug | Pazopanib- 2nd line treatment, Pazopanib- 3rd line treatment |
Primary outcome
Progression Free Survival (PFS)
Time frame: Date of first treatment to date of progression or death up to approximately 38 months
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.
6 secondary outcomes
Overall Response Rate (ORR) Based on Local Investigator Assessment According to RECIST v1.1
Time frame: Up to approximately 38 months
Clinical Benefit Rate (CBR) Based on Local Investigator Assessment According to RECIST v1.1.
Time frame: Up to approximately 38 months
Overall Survival (OS)
Time frame: From date of first treatment to date of death, up to approximately 44 months
Duration of Response (DOR) Based on Local Investigators Assessment According to RECIST v1.1
Time frame: From the date of first documented response (confirmed CR or PR) to the date of tumor progression, up to approximately 36 months
Change From Baseline in Functional Assessment of Cancer Therapy- Kidney Symptom (FKSI-DRS) Score
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
Change From Baseline in EuroQoL 5-level Instrument Visual Analogue Scale (EQ-5L-5D VAS) Score
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Aug 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- A Plain Language Trial Summary is available on novctrd.comLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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/.
Related trials for Advanced Renal Cell Carcinoma
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
Active, not recruitingPhase 3
A Study of Belzutifan (MK-6482) in Combination With Lenvatinib Versus Cabozantinib for Treatment of Renal Cell Carcinoma (MK-6482-011)
Carcinoma, Renal Cell
Not yet recruitingPhase 2
Toripalimab and Lenvatinib With or Without SBRT Before Surgery for Non-Clear Cell Kidney Cancer
Nonmetastatic Locally Advanced Non-Clear Cell Renal Cell Carcinoma
Active, not recruitingPhase 1/2
Phase 1b/2 Trial of Ipilimumab, Nivolumab, and Ciforadenant (Adenosine A2a Receptor Antagonist) in First-line Advanced Renal Cell Carcinoma.
Renal Cell Carcinoma
RecruitingPhase 2
At-Home Cancer Directed Therapy Versus in Clinic for the Treatment of Patients With Advanced Cancer
Advanced Anal Carcinoma, Advanced Biliary Tract Carcinoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
22 sites in 11 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pazopanib in people with Advanced Renal Cell Carcinoma and Metastatic Renal Cell Carcinoma, run by Novartis Pharmaceuticals at 22 sites in 11 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 22 sites in Austria, France, Germany, United Kingdom, Chile and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Mar 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression Free Survival (PFS) (time frame: Date of first treatment to date of progression or death up to approximately 38 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Aug 2023.