Clinical trial NCT03200717: 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
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
Overall status: COMPLETED
Phase: PHASE2
Conditions: 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
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2017-06-27
Enrollment: 62
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: Date of first treatment to date of progression or death up to approximately 38 months
Secondary outcomes:
measure: Overall Response Rate (ORR) Based on Local Investigator Assessment According to RECIST v1.1
timeFrame: Up to approximately 38 months
measure: Clinical Benefit Rate (CBR) Based on Local Investigator Assessment According to RECIST v1.1.
timeFrame: Up to approximately 38 months
measure: Overall Survival (OS)
timeFrame: From date of first treatment to date of death, up to approximately 44 months
measure: Duration of Response (DOR) Based on Local Investigators Assessment According to RECIST v1.1
timeFrame: From the date of first documented response (confirmed CR or PR) to the date of tumor progression, up to approximately 36 months
measure: Change From Baseline in Functional Assessment of Cancer Therapy- Kidney Symptom (FKSI-DRS) Score
timeFrame: 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
measure: Change From Baseline in EuroQoL 5-level Instrument Visual Analogue Scale (EQ-5L-5D VAS) Score
timeFrame: 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
Other outcomes:
Locations:
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Graz
country: Austria
facility: Novartis Investigative Site
city: Salzburg
country: Austria
facility: Novartis Investigative Site
city: Wien
country: Austria
facility: Novartis Investigative Site
city: Calgary
country: Canada
facility: Novartis Investigative Site
state: Alberta
city: Temuco
country: Chile
facility: Novartis Investigative Site
state: Araucania
city: Santiago
country: Chile
facility: Novartis Investigative Site
city: Brno
country: Czechia
facility: Novartis Investigative Site
state: Czech Republic
city: Olomouc
country: Czechia
facility: Novartis Investigative Site
state: CZE
city: Paris
country: France
facility: Novartis Investigative Site
city: Strasbourg Cedex
country: France
facility: Novartis Investigative Site
city: Valenciennes
country: France
facility: Novartis Investigative Site
city: Hannover
country: Germany
facility: Novartis Investigative Site
city: Jena
country: Germany
facility: Novartis Investigative Site
city: Tübingen
country: Germany
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Sevilla
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: Manchester
country: United Kingdom
facility: Novartis Investigative Site
city: Preston
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
References: