Rotating Pazopanib and Everolimus to Avoid Resistance (ROPETAR)
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|ClinicalTrials.gov Identifier: NCT01408004|
Recruitment Status : Completed
First Posted : August 2, 2011
Last Update Posted : July 16, 2014
|Condition or disease||Intervention/treatment||Phase|
|Clear Cell Renal Carcinoma||Drug: Pazopanib Drug: Everolimus||Phase 2|
Current practice is to treat with VEGFR-TKI or mTOR inhibitors until progression and then continue with the next active agent. From a biological perspective, TKI's will most likely activate compensatory pathways which, may ultimately lead to the development of resistance. Recent studies suggest that resistance to treatment with TKI may be reversible after stopping treatment. There is therefore a rationale to alternate treatment to prevent or delay the occurrence of resistance.
Our hypothesis is that alternating active agents in clear cell renal carcinoma (ccRCC) may reduce side effects, improve tolerability and compliance of treatment and prolong progression free survival and overall survival compared to the standard of care.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||101 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Randomized Phase II Study to Explore the Efficacy and Feasibility of Upfront Bi-monthly Rotations Between Everolimus and Pazopanib in Patients With Advanced or Metastatic Clear Cell Renal Cancer|
|Study Start Date :||November 2011|
|Actual Primary Completion Date :||April 2014|
|Actual Study Completion Date :||April 2014|
Experimental: Alternating regimen
In the experimental arm (Arm A) alternating treatment will consist of 8 weeks of Pazopanib 800 mg qd alternated by 8 weeks of Everolimus 10 mg qd until first progression(PD per RECIST 1.1)followed thereafter by Pazopanib (when PD after 8 weeks of Everolimus)or Everolimus (when PD after 8 weeks of Pazopanib) monotherapy until second progression.
tablet 800mg qd, alternating schedule: 8 weeks Pazopanib, 8 weeks Everolimus
tablet 10mg qd, alternating schedule: 8 weeks Pazopanib, 8 weeks Everolimus
Everolimus 10mg qd monotherapy until second progression (PD per RECIST 1.1)when first progression after 8 weeks of Pazopanib in alternating regimen
Pazopanib 800mg qd monotherapy until second progression (PD per RECIST 1.1) when first progression after 8 weeks of Everolimus in alternating regimen
Active Comparator: Sequential treatment
The comparative arm (Arm B) will be the standard regimen of Pazopanib (800 mg qd continuously) until progression, followed thereafter by Everolimus (10 mg qd continuously) until progression.
Tablet 800mg qd til progression
tablet 10 mg qd til progression
- Progression free survival [ Time Frame: Randomization until earliest date of disease progression (according RECIST 1.1 criteria) or death, an expected average of one year ]
- Time to second progression [ Time Frame: Time between first and second progression, an expected average of five months ]Time between first progression and second progression (PD) per RECIST 1.1 on Everolimus monotherapy (when PD after 8 weeks Pazopanib) or Pazopanib monotherapy (when PD after 8 weeks Everolimus) as second line treatment in experimental arm and time to progressive disease on Everolimus as second line treatment in comparative arm.
- Change in Quality of life assessed by the FKSI-DRS and EORTC QLQ-C30 questionnaires compared to baseline [ Time Frame: From randomization until one month after ceasing study medication, an expected average of 18 months ]Quality of life will be assessed bi-monthly by using the FACT Kidney Symptom Index (FKSI)-Disease Related Symptom (DRS)and the EORTC QLQ-C30 questionnaire. The symptoms covered by the FKSI-DRS include fatigue, pain, weight loss, dyspnea, cough, fever and hematuria. The EORTC QLQ-C30 questionnaire evaluates five functional scales (physical, role, emotional, social and cognitive functioning), three symptom scales (fatigue, pain, nausea, and vomiting), a global health status/QoL scale, and six single items (dyspnea, diarrhea, constipation, anorexia, insomnia and financial impact).
- Toxicity reported as number/percentage of patients with adverse events [ Time Frame: From randomization until one month after ceasing study medication, an expected average of 18 months ]Adverse events will be reported according Criteria for Adverse Events v4.0 (NCI CTCAE v4)
- Overall survival [ Time Frame: Time between randomization and death, an estimated average of 2-5 years ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01408004
|St. Franciscus Gasthuis|
|Rotterdam, Zuid-Holland, Netherlands|
|Medisch Centrum Alkmaar|
|Acedemisch Medisch Centrum Amsterdam|
|Amphia ziekenhuis Breda|
|Den Haag, Netherlands|
|Maxima Medisch Centrum|
|Atrium Medisch Centrum Heerlen|
|Medische Centrum Leeuwarden|
|Acedemisch ziekenhuis Maastricht|
|St. Antonius ziekenhuis|
|Erasmus Medisch Centrum|
|Orbis Medisch Centrum|
|St. Elisabeth ziekenhuis|
|Utrecht, Netherlands, 3508 GA|
|Principal Investigator:||E.E. Voest, MD/PhD||UMC Utrecht|