Validation of the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) Prognostic Classification for Targeted Therapies (TKI/mTOR Inhibitors) in Second Line After First Line Treatment With Pazopanib

Completed

• Conditions: Metastatic Renal Cell Carcinoma

• Registration Number: NCT03091465
• Lead Sponsor: Spanish Oncology Genito-Urinary Group

Brief Summary

This is a nation-wide retrospective observational study which will be performed in 50 centres in Spain, geographically representative of all regions, with at least 5 patients treated with first-line pazopanib for mRCC in daily clinical practice since April 2011 (date of approval of pazopanib in Spain), January 2016.

Pazopanib is one of the standard tyrosine-kinase inhibitors (TKI) for the first-line treatment of metastatic renal cell carcinoma. In our previous SPAZO study, the Spanish Oncologic Genitourinary Group (SOGUG) validated the IMDC prognostic classification for patients receiving first-line pazopanib, and demonstrated the effectiveness of this drug in routine clinical practice. However, in this series of 278 patients, we could not obtain enough information on the effectiveness of pazopanib in special subpopulations such as non-clear cell histologies, and others subgroups, due to a small simple size of each of these subpopulations. On the other hand, after the results of RECORD-1 and AXIS trials, switching to everolimus or axitinib is the current approach for patients who progresses to a first-line TKI. However, these pivotal studies did not include patients treated with first-line pazopanib study because this drug was not available at that time. The results of the SPAZO study also suggested that the effectiveness of second-line targeted therapies (TT) after pazopanib in routine clinical practice is similar to the observed in clinical trials after sunitinib, sorafenib or bevacizumab. In addition, the preliminary results indicated that there are not meaningful differences in the effectiveness of TKI or mTOR inhibitors after pazopanib, when the results are adjusted by the IMDC prognostic classification. However, the IMDC prognostic classification for second-line TT has not yet been validated for patients who receive pazopanib as first-line. In addition our sample size was not large enough to make a comparison of effectiveness between mTOR inhibitors and antiVEGF for each prognostic subgroups of the IMDC.

Based on that, the Spanish Oncologic Genitourinary Group has decided to launch the SPAZO-2 study, in which we intend to prolong the follow up of patients included in SPAZO, and to increase the sample size with new patients from new centres, in order to obtain a larger sample in each of the subpopulations of interest, with the objective of obtaining more information about the above questions.

Detailed Description

Not available

Study Timeline

• Study Start: 2016-12-20
• Study First Submitted: 2017-03-02
• Study First Submitted QC: 2017-03-21
• Study First Posted: 2017-03-27
• Primary Completion: 2017-04-17
• Study Completion: 2017-04-17
• Status Verified: 2018-04
• Last Update Submitted: 2018-04-25
• Last Update Posted: 2018-04-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 530

Inclusion Criteria

• 1. Patients with confirmed mRCC. All histologies are allowed.
• 2. Patients who have received pazopanib in their centre as first TKI for metastatic renal carcinoma in daily clinical practice since its approval in Spain until January 2016 (previous non-TKI therapies such as surgery for metastasis, local radiotherapy, citokines or chemotherapy are allowed.
• 3. Age ≥18 years.
• 4. Patients alive should give informed consent to participate in the study and to allow their medical records to be reviewed, preferably in writing o orally before independent witnesses of the research team and after being informed and have sufficient time to decide on their inclusion in the study

Exclusion Criteria

• 1. Patients who received pazopanib in any clinical trial, or who had received any systemic therapy prior to pazopanib will not be included, except citoquines or sunitinib providing it had been given as first-line, and switched to pazopanib due to toxicity or intolerance during the first cycle.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
IMDC prognostic	1 day	Validate the IMDC prognostic classification in terms of overall survival, for second line treatment with mTOR/TKI inhibitors after first-line pazopanib. Overall survival defined as the period between second-line targeted therapy initiation and the date of death or censored on the day of last follow up visit, will be indirectly compared to the reported in the IMDC for the overall population and for each IMDC subgroups.

Secondary Outcome Measures

Name	Time	Method
Effectiveness of pazopanib administered in the first-line setting of mRCC patients in terms of OS.	1 day
Effectiveness of mTOR inhibitors versus antiangiogenic TKI inhibitors in second-line after progression to pazopanib in the first-line setting of mRCC patients in terms of overall survival (OS).	1 day
Effectiveness of mTOR inhibitors versus antiangiogenic TKI inhibitors in second-line after progression to pazopanib in the first-line setting of mRCC patients in terms of response rate (RR).	1 day
Effectiveness of mTOR inhibitors versus antiangiogenic TKI inhibitors in second-line after progression to pazopanib in the first-line setting of mRCC patients in terms of progression-free survival (PFS).	1 day
Safety of pazopanib and mTOR/TKI inhibitors evaluated as the number of patients who present treatment-related adverse events as assessed by CTCAE v4.0.	1 day
Effectiveness of pazopanib administered in the first-line setting of mRCC patients in terms of PFS.	1 day
Effectiveness of pazopanib administered in the first-line setting of mRCC patients in terms of RR.	1 day

Trial Locations

Locations (57)

Hospital General Universitario de Elche; 🇪🇸 Elche, Alicante, Spain

Hospital Germans Trias i Pujol; 🇪🇸 Badalona, Barcelona, Spain

Corporació Sanitària Parc Taulí; 🇪🇸 Sabadell, Barcelona, Spain

Hospital Universitario Mútua Terrassa; 🇪🇸 Terrassa, Barcelona, Spain

Onkologikoa; 🇪🇸 San Sebastian, Guipúzcoa, Spain

Complejo Hospitalario de Jaén; 🇪🇸 Jaen, Jaén, Spain

Hospital Clínico Universitario de Santiago; 🇪🇸 Santiago de Compostela, La Coruña, Spain

Hospital Universitario de Gran Canaria Dr. Negrin; 🇪🇸 Las Palmas de Gran Canaria, Las Palmas, Spain

Hospital Universitario de León; 🇪🇸 Leon, León, Spain

Hospital Universitario Severo Ochoa; 🇪🇸 Leganes, Madrid, Spain

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