Pazopanib in Second-line Therapy in Renal Cell Carcinoma

A Phase II, Opened, Not Controlled and Multicentric Clinical Trial of Pazopanib in Monotherapy to Determine Efficiency and Safety in Second-line of Treatment in Patients With Carcinoma of Advanced Renal Cells That Have Progressed or Have Not Tolerated the First Line of Treatment With Tyrosine Kinase Inhibitor

The principal aim of the study is to determine the objective response rate that offers the second-line treatment with pazopanib in patients with carcinoma of advanced renal cells that have progressed or that have not tolerated the first line of treatment with a Tyrosine Kinase Inhibitor. The secondary aims are to determine the overall survival and the treatment safety profile for these patients in second-line treatment with pazopanib. The exploratory aim is to determine the correlation between biomarkers in patient blood and tumor samples, and the clinical results obtained with pazopanib.

Study Overview

• Status: Unknown
• Conditions: Metastatic Renal Cell Carcinoma
• Intervention / Treatment: Drug: Pazopanib

Detailed Description

Patients who progress or do not tolerate a first-line treatment with a Tyrosine Kinase Inhibitor will be included consecutively in the study. All patients will receive the same treatment regimen consisting of 800 mg / day of pazopanib in monotherapy.

All patients will receive treatment until there is evidence of progression, evidence of unacceptable toxicity, not compliance, investigator clinical decision or consent withdrawal by the patient.

After treatment, the patient will enter to the follow-up period. During this period the investigator will collect information from subsequent administered treatments and survival of all patients, regardless of the reason for withdrawal, every 8 weeks until the scheduled end of follow-up period, according to protocol. At 30 days after treatment completion, the first follow up visit will be scheduled to assess the possible occurrence of late toxicity. In those patients who complete treatment prior to objectify progression, information about the progression of the disease will be collected.

• Study Type: Interventional
• Enrollment (Anticipated): 27
• Phase: Phase 2

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08003
    • Hospital del Mar
  • Barcelona, Spain, 08025
    • Hospital De La Santa Creu I Sant Pau
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos
  • Madrid, Spain, 28009
    • Hospital General Universitario Gregorio Marañón
  • Madrid, Spain, 28026
    • Hospital 12 de Octubre
  • Asturias
    • Oviedo, Asturias, Spain, 33006
      • Hospital Universitario Central de Asturias
  • Baleares
    • Palma de Mallorca, Baleares, Spain, 07010
      • Hospital Universitari Son Espases
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Hospital Universitari Germans Trias i Pujol
    • Hospitalet de Llobregat, Barcelona, Spain, 08907
      • Hospital De Bellvitge
    • Sabadell, Barcelona, Spain, 08208
      • Corporacio Sanitaria Parc Tauli

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Signed Inform Consent
2. Age ≥ 18
3. Histologically confirmed diagnosis of clear cell renal carcinoma metastatic or locally recurrent unresectable.
4. Patients must have received only a first-line treatment with a Tyrosine Kinase Inhibitor. Patients must have progressed during treatment or within three months after stopping treatment with these agents. Patients who discontinued treatment with a Tyrosine Kinase Inhibitor for unacceptable toxicity are also eligible for the study.
5. Patients must have been previously treated by nephrectomy with removal of the primary tumor, except that there is a contraindication (eg liver I extensive bone metastatic disease or primary tumor smaller than 5 cm).
6. Patients with ECOG PS 0 or 1.
7. To be included in the study, the renal tumor should be classified in a group of low or intermediate risk according to the Motzer classification.
8. Eligibility criteria under RECIST v.1.1

9. Adequate hematologic function:

   Absolute neutrophil count ≥ 1.5 x 109 / L Platelet count ≥ 100 x 109 / L Hemoglobin ≥ 9 g / dL (5.6 mmol / L). Prothrombin time (PT) or international normalized ratio (INR) ≤ 1.2 X ULN. Activated partial thromboplastin time (APTT) ≤ 1.2 X ULN

10. Adequate hepatic function:

    total bilirubin ≤ 1.5 X ULN ALT ≤ 2.5 x ULN

11. Adequate renal function:

    Serum creatinine ≤ or 1.5 mg / dL (133 mol / L). If> 1.5 mg / dL, then the calculated creatinine clearance has to be ≥ 50 mL / min (Appendix 1).

    Urine protein / creatinine ratio <1.

12. Can be included in the study of both fertile and infertile women.

Exclusion Criteria:

1. Previous malignancy. May be included in the study patients with a disease-free interval of 5 years at the time of inclusion in the study and patients with non-melanoma skin carcinoma completely resected or carcinoma in situ treated successfully.
2. Previous treatment with more then one Tyrosine Kinase Inhibitor or more than one previous traditional regime (eg, chemotherapy, immunotherapy or chemo-immunotherapy).
3. Known history or clinical evidence of nervous system metastases or leptomeningeal carcinomatosis, except that metastases in the central nervous system have been previously treated, are asymptomatic and not requiring treatment with corticosteroids or anticonvulsant medication within six months before the first administration of pazopanib.
4. Clinically significant gastrointestinal disorders that may increase the risk of bleeding gastrointestinal.
5. Clinically significant gastrointestinal disorders which may affect the absorption of pazopanib.
6. Presence of uncontrolled infection.
7. ECG QT interval longer than 480 milliseconds, according to the Bazett formula.

8. History of one or more of the following cardiovascular conditions within the last 6 months prior to inclusion:

   Cardiac angioplasty or stent placement Myocardial infarction Unstable angina Surgery or coronary bypass Symptomatic peripheral vascular disease

9. Congestive heart failure Class III or IV, as defined by the New York Heart Association
10. Poorly controlled hypertension (defined as systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg).
11. History of stroke (including transient ischemic attack), pulmonary embolism or deep vein thrombosis not treated within 6 months.
12. Major surgery or major trauma within 28 days prior to administering the first dose of study and / or presence of any unhealed wound, fracture, or ulcer (not considered major procedures such as venous catheter placement with or without a reservoir).
13. Evidence of bleeding diathesis or active bleeding.
14. Endobronchial lesions known and / or lesions infiltrating major pulmonary vessels.
15. Hemoptysis greater than 2.5 milliliters in the 8 weeks before the first administration of study drug.
16. Any medical condition, psychiatric or any other nature, unstable or severe, which could interfere with patient safety, with the ability to give informed consent or compliance with study procedures.
17. Inability or lack of willingness to discontinue the use of banned drugs listed in in the previous 14 days, or the time equivalent to 5 half-lives (whichever is greater) at baseline and during treatment with pazopanib.
18. Treatment with any of the following antineoplastic therapy: radiation therapy, surgery, tumor embolization, chemotherapy, immunotherapy, biologic therapies, investigational therapies or hormone treatments within 14 days, or the time equivalent to 5 half-lives (whichever is greater), to the administration of the first dose of pazopanib.
19. Any unresolved toxicity from previous cancer therapies> Grade 1 and / or is getting worse in intensity, except for alopecia.
20. Patients who are at risk of hypersensitivity to pazopanib.
21. Pregnant or lactating women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pazopanib; 800 mg / day of pazopanib in monotherapy	Drug: Pazopanib; 800 mg / day of pazopanib in monotherapy.; Other Names: Pazopanib (GW786034; Votrient®)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate	To asses the Objective Response (Complete Response or Partial Response) which provides second-line treatment with pazopanib in patients with carcinoma of advanced renal cell who have progressed or have not tolerated a first line of treatment with a Tyrosine Kinase Inhibitor. The Objective Response Rate will be evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.	30 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	To assess the overall survival in patients treated with second-line treatment with pazopanib.	30 months
Treatment Safety Profile	To assess the treatment safety profile in patients treated with second-line treatment with pazopanib. Safety was assessed using Common Toxicity Criteria (CTC) of the National Cancer Institute (NCI), version 4.0.	30 months

Collaborators and Investigators

• Sponsor: Associació per a la Recerca Oncologica, Spain
• Collaborators: Trial Form Support S.L.
• Investigators: Principal Investigator: José Luis González Larriba, MD, Hospital San Carlos, Madrid; Study Chair: Joaquim Bellmunt, MD, Hospital del Mar; Principal Investigator: Marta Guix, MD, Hospital del Mar; Principal Investigator: Juan Manuel Sepúlveda, MD, Hospital 12 de Octubre; Principal Investigator: Enrique Gallardo, MD, Corporacio Sanitaria Parc Tauli; Principal Investigator: Xavier García del Muro, MD, Hospital Universitari de Bellvitge; Principal Investigator: Olatz Etxaniz, MD, Germans Trias i Pujol Hospital; Principal Investigator: Jose Angel Arranz, MD, Hospital General Universitario Gregorio Marañón; Principal Investigator: Emilio Esteban, MD, Hospital Universitario Central de Asturias; Principal Investigator: Aranzazu González del Alba, MD, Hospital Son Espases; Principal Investigator: Pablo Maroto, MD, Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (Anticipated): October 1, 2014
• Study Completion (Anticipated): October 1, 2015

Study Registration Dates

• First Submitted: April 10, 2012
• First Submitted That Met QC Criteria: April 13, 2012
• First Posted (Estimate): April 16, 2012

Study Record Updates

• Last Update Posted (Estimate): March 12, 2014
• Last Update Submitted That Met QC Criteria: March 11, 2014
• Last Verified: March 1, 2014

More Information

Terms related to this study

• Keywords: Advanced renal cell carcinoma; second-line treatment with pazopanib; first line of treatment with a Tyrosine Kinase Inhibitor
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Carcinoma, Renal Cell; Carcinoma
• Other Study ID Numbers: APRO02-2011