Clinical trial NCT03091465: 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
Official title: 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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Metastatic Renal Cell Carcinoma
Lead sponsor: Spanish Oncology Genito-Urinary Group
Sponsor class: OTHER
First posted: 2017-03-27
Enrollment: 530
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: metastatic renal cell carcinoma patients treated with pazopanib as first line treatment and target therapies (TKI/mTOR inhibitors) in second line

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.


Eligibility criteria: 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.

Primary outcomes:
measure: IMDC prognostic
timeFrame: 1 day
Secondary outcomes:
measure: 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).
timeFrame: 1 day
measure: 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).
timeFrame: 1 day
measure: 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).
timeFrame: 1 day
measure: Effectiveness of pazopanib administered in the first-line setting of mRCC patients in terms of OS.
timeFrame: 1 day
measure: Effectiveness of pazopanib administered in the first-line setting of mRCC patients in terms of PFS.
timeFrame: 1 day
measure: Effectiveness of pazopanib administered in the first-line setting of mRCC patients in terms of RR.
timeFrame: 1 day
measure: 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.
timeFrame: 1 day
Other outcomes:
Locations:
city: Elche
country: Spain
facility: Hospital General Universitario de Elche
state: Alicante
city: Badalona
country: Spain
facility: Hospital Germans Trias i Pujol
state: Barcelona
city: Sabadell
country: Spain
facility: Corporació Sanitària Parc Taulí
state: Barcelona
city: Terrassa
country: Spain
facility: Hospital Universitario Mútua Terrassa
state: Barcelona
city: San Sebastian
country: Spain
facility: Onkologikoa
state: Guipúzcoa
city: Jaen
country: Spain
facility: Complejo Hospitalario de Jaén
state: Jaén
city: Santiago de Compostela
country: Spain
facility: Hospital Clínico Universitario de Santiago
state: La Coruña
city: Las Palmas de Gran Canaria
country: Spain
facility: Hospital Universitario de Gran Canaria Dr. Negrin
state: Las Palmas
city: Leon
country: Spain
facility: Hospital Universitario de León
state: León
city: Leganes
country: Spain
facility: Hospital Universitario Severo Ochoa
state: Madrid
city: Pozuelo de Alarcon
country: Spain
facility: Hospital Universitario Quirón
state: Madrid
city: San Sebastian de los Reyes
country: Spain
facility: Hospital Universitario Infanta Sofía
state: Madrid
city: Palma de Mallorca
country: Spain
facility: Hospital de Son Llàtzer
state: Mallorca
city: Palma de Mallorca
country: Spain
facility: Hospital Universitario Son Espases
state: Mallorca
city: Orense
country: Spain
facility: Complexo Hospitalario Universitario de Ourense
state: Ourense
city: Vigo
country: Spain
facility: Hospital Álvaro Cunqueiro
state: Pontevedra
city: Reus
country: Spain
facility: Hospital Universitari Sant Joan de Reus
state: Tarragona
city: San Cristobal de La Laguna
country: Spain
facility: Hospital Universitario de Canarias
state: Tenerife
city: Santa Cruz de Tenerife
country: Spain
facility: Hospital Universitario Nuestra Señora de Candelaria
state: Tenerife
city: Alcira
country: Spain
facility: Hospital Universitario de La Ribera
state: Valencia
city: Bilbao
country: Spain
facility: Hospital de Basurto
state: Vizcaya
city: Bilbao
country: Spain
facility: Clínica IMQ Zorrotzaurre
state: Vizcaya
city: Alicante
country: Spain
facility: Hospital General Universitario de Alicante
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Universitario Vall D'Hebron
city: Barcelona
country: Spain
facility: Hospital Clínic i Provincial de Barcelona
city: Burgos
country: Spain
facility: Hospital Universitario de Burgos
city: Caceres
country: Spain
facility: Hospital San Pedro de Alcántara
city: Ciudad Real
country: Spain
facility: Hospital General Universitario de Ciudad Real
city: Cordoba
country: Spain
facility: Hospital Universitario Reina Sofía
city: Granada
country: Spain
facility: Hospital Universitario Clínico San Cecilio
city: Granada
country: Spain
facility: Hospital Universitario Virgen de las Nieves
city: Guadalajara
country: Spain
facility: Hospital Universitario de Guadalajara
city: Huelva
country: Spain
facility: Hospital Juan Ramón Jimenez
city: Lugo
country: Spain
facility: Hospital Universitario Lucus Augusti
city: Madrid
country: Spain
facility: Hospital La Luz
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón
city: Madrid
country: Spain
facility: Fundación Jiménez Díaz
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Madrid
country: Spain
facility: Hospital Central de la Defensa "Gómez-Ulla"
city: Madrid
country: Spain
facility: Hospital Universitario Puerta de Hierro
city: Pontevedra
country: Spain
facility: Hospital Provincial de Pontevedra
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen de la Macarena
city: Sevilla
country: Spain
facility: Hospital Virgen del Rocío
city: Sevilla
country: Spain
facility: Hospital Nuestra Señora de Valme
city: Toledo
country: Spain
facility: Hospital Virgen de la Salud
city: Valencia
country: Spain
facility: Instituto Valenciano de Oncología
city: Valencia
country: Spain
facility: Hospital Clinico de Valencia
city: Valencia
country: Spain
facility: Hospital Universitario Doctor Peset
city: Valencia
country: Spain
facility: Hospital Universitario y Politécnico de La Fe
city: Valladolid
country: Spain
facility: Hospital Universitario Río Hortega
city: Zaragoza
country: Spain
facility: Hospital Clínico Universitario Lozano Blesa
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
Study officials:
References:
citation: Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010 Dec 15;127(12):2893-917. doi: 10.1002/ijc.25516.
citation: Rini BI, Campbell SC, Escudier B. Renal cell carcinoma. Lancet. 2009 Mar 28;373(9669):1119-32. doi: 10.1016/S0140-6736(09)60229-4. Epub 2009 Mar 5.