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Completed

NCT Number: 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

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).

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Key information

Conditions

Advanced Renal Cell Carcinoma Adenocarcinoma Carcinoma Carcinoma, Renal Cell Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Kidney Diseases Kidney Neoplasms Male Urogenital Diseases Metastatic Renal Cell Carcinoma Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Glandular and Epithelial Urogenital Diseases Urogenital Neoplasms Urologic Diseases Urologic Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Novartis Investigative Site, Caba, Buenos Aires, Argentina

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Pazopanib

Drug

Participants received 800mg of pazopanib once daily orally. Pazopanib was supplied as aqueous film-coated tablets containing 200 mg or 400 mg.

Primary outcomes

  1. 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.

Secondary outcomes

  1. Overall Response Rate (ORR) Based on Local Investigator Assessment According to RECIST v1.1

    Time frame: Up to approximately 38 months

    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.

  2. Clinical Benefit Rate (CBR) Based on Local Investigator Assessment According to RECIST v1.1.

    Time frame: Up to approximately 38 months

    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.

  3. Overall Survival (OS)

    Time frame: From date of first treatment to date of death, up to approximately 44 months

    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.

  4. 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

    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.

  5. 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

    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.

  6. 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

    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.

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Registry information

Official study 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

Acronym: IO-PAZ

Important dates

Study start
2017
Primary completion
2021
Study completion
2021
First posted
Jun 27, 2017
Registry last updated
Aug 21, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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