IO-PAZ: 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

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT03200717

Collaborator

(none)

Enrollment

Locations

Arm

44.8

Actual Duration (Months)

2.8

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

An international, multicenter, single arm Phase II trial to determine the efficacy, safety and quality of life of pazopanib treatment after previous therapy with immune checkpoint treatment. Approximately 100 patients will be enrolled, with approximately 40 of those patients receiving pazopanib as 2nd-line therapy. Patients will receive treatment with standard dose pazopanib until disease progression, unacceptable toxicity, pregnancy, death, discontinuation from the study treatment for any other reason or until study end. All patients will be followed for survival. Patients who discontinue treatment without documented disease progression will be followed for efficacy.

Condition or Disease	Intervention/Treatment	Phase
Advanced Renal Cell Carcinoma Metastatic Renal Cell Carcinoma	Drug: pazopanib	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

62 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

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

Actual Study Start Date :

Nov 14, 2017

Actual Primary Completion Date :

Aug 10, 2021

Actual Study Completion Date :

Aug 10, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: pazopanib 800 mg administered after checkpoint inhibitor treatment	Drug: pazopanib Pazopanib is taken orally and will be administered daily as a fixed dose. Enrollment of 3rd-line patients will be restricted to ensure approximately 40 patients receive pazopanib as 2nd-line therapy. Number of Cycles: until progression, unacceptable toxicity develops, death, pregnancy, start of new anti-cancer therapy, doctor/patient discontinuation, lost to follow-up, end of study, or study termination by sponsor.

Arm

Intervention/Treatment

Experimental: pazopanib 800 mg

administered after checkpoint inhibitor treatment

Drug: pazopanib

Pazopanib is taken orally and will be administered daily as a fixed dose. Enrollment of 3rd-line patients will be restricted to ensure approximately 40 patients receive pazopanib as 2nd-line therapy. Number of Cycles: until progression, unacceptable toxicity develops, death, pregnancy, start of new anti-cancer therapy, doctor/patient discontinuation, lost to follow-up, end of study, or study termination by sponsor.

Outcome Measures

Primary Outcome Measures

Progression free survival based on local investigator assessment [Date of first treatment to date of progression or death up to approximately 44 months]
Progression free survival (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 will be assessed via local review according to RECIST 1.1.

Secondary Outcome Measures

Overall response rate based on local investigator assessment [Up to approximately 44 months]
Overall response rate defined as the proportion of patients with best overall response of confirmed complete response (CR) or partial response (PR) based on local investigator's assessment according to RECIST v1.1
Clinical Benefit rate based on local investigator assessment [Up to approximately 44 months]
Clinical benefit rate defined as the proportion of patients 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.
Overall survival [From date of first treatment to date of death, up to approximately 44 months]
Overall survival defined as the time from the first administration of study treatment until death due to any cause
Duration of response in patients with confirmed complete response or partial response [From the date of first documented response (confirmed CR or PR) to the date of tumor progression, up to approximately 44 months]
Duration of response 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.
Number of participants with treatment-emergent Adverse Events (TEAEs) [From date of first dose of treatment to 30 days after last dose of study medication, up to approximately 44 months]
Type, frequency and severity of TEAEs per National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE) v4.03, including laboratory toxicities.
Change from baseline in Functional Assessment of Cancer Therapy- Kidney Symptom (FSKI-DRS) score [From baseline until the end of treatment, approximately up to approximately 44 months]
Quality of life measured through the Functional Assessment of Cancer Therapy- Kidney Symptom Index (FSKI-DRS). FKSI-DRS is a validated tool developed specifically to assess symptoms experienced by patients with advanced kidney cancer. The symptoms covered by the 9-item FKSI-DRS include fatigue, pain, weight loss, dyspnea, cough, fever and hematuria. Each item is scored on a 5-point scale (0=not at all to 4=very much). FKSI-DRS total score ranged from 0 (most severe symptoms) to 36 (no symptoms) with a higher score indicating a better outcome.
Change from baseline in EuroQoL 5-level instrument (EQ-5D-5L) score [From baseline until the end of treatment, approximately up to approximately 44 months]
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). EQ-5D health state profile is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: 1= no problems, 2= slight problems, 3=moderate problems, 4= severe problems, and 5= extreme problems. Higher scores indicated greater levels of problems across each of the five dimensions.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
2	Novartis Investigative Site	Caba	Buenos Aires	Argentina	C1280AEB
3	Novartis Investigative Site	Graz		Austria	8036
4	Novartis Investigative Site	Salzburg		Austria	5020
5	Novartis Investigative Site	Wien		Austria	A-1090
6	Novartis Investigative Site	Calgary	Alberta	Canada	T2N 4N2
7	Novartis Investigative Site	Temuco	Araucania	Chile	4810469
8	Novartis Investigative Site	Santiago		Chile	8420383
9	Novartis Investigative Site	Brno	Czech Republic	Czechia	656 53
10	Novartis Investigative Site	Olomouc	CZE	Czechia	775 20
11	Novartis Investigative Site	Paris		France	75015
12	Novartis Investigative Site	Strasbourg Cedex		France	F 67098
13	Novartis Investigative Site	Valenciennes		France	59300
14	Novartis Investigative Site	Hannover		Germany	30625
15	Novartis Investigative Site	Jena		Germany	07740
16	Novartis Investigative Site	Tübingen		Germany	72076
17	Novartis Investigative Site	Budapest		Hungary	H 1122
18	Novartis Investigative Site	Sevilla	Andalucia	Spain	41013
19	Novartis Investigative Site	Madrid		Spain	28041
20	Novartis Investigative Site	London		United Kingdom	NW3 2QG
21	Novartis Investigative Site	Manchester		United Kingdom	M20 2BX
22	Novartis Investigative Site	Preston		United Kingdom	PR2 9HT