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

Metastatic Renal Cell Carcinoma Clinical Trial

— Spazo-2  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03091465
• Other study ID #: SOGUG-2016-A-IEC(REN)-4
• Secondary ID: SOG-PAZ-2016-01
• Status: Completed
• First received: March 2, 2017
• Last updated: April 25, 2018
• Start date: December 20, 2016
• Est. completion date: April 17, 2017

Study information

• Verified date: April 2018
• Source: Spanish Oncology Genito-Urinary Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 530
• Est. completion date: April 17, 2017
• Est. primary completion date: April 17, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell
• Metastatic Renal Cell Carcinoma

Locations

Country	Name	City	State
Spain	Hospital Universitario de La Ribera	Alcira	Valencia
Spain	Hospital General Universitario de Alicante	Alicante
Spain	Hospital Germans Trias i Pujol	Badalona	Barcelona
Spain	Hospital Clínic i Provincial de Barcelona	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital del Mar	Barcelona
Spain	Hospital Universitario Vall D'Hebron	Barcelona
Spain	Clínica IMQ Zorrotzaurre	Bilbao	Vizcaya
Spain	Hospital de Basurto	Bilbao	Vizcaya
Spain	Hospital Universitario de Burgos	Burgos
Spain	Hospital San Pedro de Alcántara	Caceres
Spain	Hospital General Universitario de Ciudad Real	Ciudad Real
Spain	Hospital Universitario Reina Sofía	Cordoba
Spain	Hospital General Universitario de Elche	Elche	Alicante
Spain	Hospital Universitario Clínico San Cecilio	Granada
Spain	Hospital Universitario Virgen de las Nieves	Granada
Spain	Hospital Universitario de Guadalajara	Guadalajara
Spain	Hospital Juan Ramón Jimenez	Huelva
Spain	Complejo Hospitalario de Jaén	Jaen	Jaén
Spain	Hospital Universitario de Gran Canaria Dr. Negrin	Las Palmas de Gran Canaria	Las Palmas
Spain	Hospital Universitario Severo Ochoa	Leganes	Madrid
Spain	Hospital Universitario de León	Leon	León
Spain	Hospital Universitario Lucus Augusti	Lugo
Spain	Fundación Jiménez Díaz	Madrid
Spain	Hospital Central de la Defensa "Gómez-Ulla"	Madrid
Spain	Hospital Clínico San Carlos	Madrid
Spain	Hospital General Universitario Gregorio Marañón	Madrid
Spain	Hospital La Luz	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Puerta de Hierro	Madrid
Spain	Complexo Hospitalario Universitario de Ourense	Orense	Ourense
Spain	Hospital de Son Llàtzer	Palma de Mallorca	Mallorca
Spain	Hospital Universitario Son Espases	Palma de Mallorca	Mallorca
Spain	Hospital Provincial de Pontevedra	Pontevedra
Spain	Hospital Universitario Quirón	Pozuelo de Alarcon	Madrid
Spain	Hospital Universitari Sant Joan de Reus	Reus	Tarragona
Spain	Corporació Sanitària Parc Taulí	Sabadell	Barcelona
Spain	Hospital Universitario de Salamanca	Salamanca
Spain	Hospital Universitario de Canarias	San Cristobal de La Laguna	Tenerife
Spain	Onkologikoa	San Sebastian	Guipúzcoa
Spain	Hospital Universitario Infanta Sofía	San Sebastian de los Reyes	Madrid
Spain	Hospital Universitario Nuestra Señora de Candelaria	Santa Cruz de Tenerife	Tenerife
Spain	Hospital Clínico Universitario de Santiago	Santiago de Compostela	La Coruña
Spain	Hospital Nuestra Señora de Valme	Sevilla
Spain	Hospital Universitario Virgen de la Macarena	Sevilla
Spain	Hospital Virgen del Rocío	Sevilla
Spain	Hospital Universitario Mútua Terrassa	Terrassa	Barcelona
Spain	Hospital Virgen de la Salud	Toledo
Spain	Hospital Clinico de Valencia	Valencia
Spain	Hospital Universitario Doctor Peset	Valencia
Spain	Hospital Universitario y Politécnico de La Fe	Valencia
Spain	Instituto Valenciano de Oncología	Valencia
Spain	Hospital Universitario Río Hortega	Valladolid
Spain	Hospital Álvaro Cunqueiro	Vigo	Pontevedra
Spain	Hospital Clínico Universitario Lozano Blesa	Zaragoza
Spain	Hospital Universitario Miguel Servet	Zaragoza

Sponsors (1)

Lead Sponsor	Collaborator
Spanish Oncology Genito-Urinary Group

Country where clinical trial is conducted

Spain, 

References & Publications (2)

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. — View 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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	IMDC prognostic	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.	1 day
Secondary	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
Secondary	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
Secondary	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
Secondary	Effectiveness of pazopanib administered in the first-line setting of mRCC patients in terms of OS.		1 day
Secondary	Effectiveness of pazopanib administered in the first-line setting of mRCC patients in terms of PFS.		1 day
Secondary	Effectiveness of pazopanib administered in the first-line setting of mRCC patients in terms of RR.		1 day
Secondary	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