Pazopanib in Combination With Interferon Alfa 2-A, in Patients With Advanced Renal Cell Carcinoma

Study Overview
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Brief Summary
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Phase I / II, open, prospective, multicenter single-arm, Clinical Trial in two stages: in the first stage it will determine the optimal dose of the combination of pazopanib and interferon alfa-A2 in the treatment of patients with advanced renal carcinoma and a second stage that will determine the efficacy of this combination measured in terms of response rate.

Official Title
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Phase I/II Prospective, Open Label and Multicentric Clinical Trial to Determine the Recommended Dose (Phase I) and Efficacy of Pazopanib in Combination With Interferon Alfa 2-A (Phase II), in Patients With Advanced Renal Cell Carcinoma

Conditions
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Advanced Renal Cell Carcinoma

Intervention / Treatment
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* Drug: Pazopanib + interferon alpha 2A


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent Age ≥ 18 years. Patients diagnosed histologically clear cell carcinoma of the kidney metastatic or unresectable locally advanced, previously untreated. However, in Phase I may include patients with primary tumors other than renal cell can benefit from these drugs and patients with renal cell carcinoma treated before. Performance status (ECOG) 0-1. Patients must have measurable disease by RECIST criteria V 1.1. Progression should be documented in the two months prior to study entry. Patients may not have received prior treatment with anti-VEGF agents, mTOR inhibitors or cytokines. However, in Phase I may include patients who have received any previous treatment. Paraffin tumor sample should be available and collection of serum from all subjects for biomarker analysis previously and / or during treatment with study medication. Adequate Hematologic, liver and kidney functions. Women of childbearing potential must be using an effective method of birth control (abstinence, any intrauterine device [IUD] published data showing that the expected minimum rate of failure is less than 1% per year, or any other method the published data show that the expected minimum rate of failure is less than 1% per year) before inclusion in the study and continue using it during the same six months after completion. Women of childbearing age should get a negative pregnancy test in urine or serum (minimum sensitivity 25 IU / L or equivalent units of beta fraction of human chorionic gonadotropin [β-HCG]) during the seven days prior to the randomization. Able to swallow oral compound. Willingness and ability to attend scheduled visits, to follow the treatment schedule and to undergo clinical trials and other study procedures Exclusion Criteria: History of prior malignancies diagnosed or treated over the past 5 years except basal cell skin cancer or prostate cancer incidentally detected previously treated. However, patients with a history of malignancy but free of the disease over the past 5 years, or patients with a history of nonmelanoma skin carcinoma-completely-resected or carcinoma in situ treated successfully can participate in the study . In Phase I, patients diagnosed with other previous or concomitant malignant diseases can be included. Presence of metastases in the central nervous system (CNS) or leptomeningeal carcinomatosis, except for patients with previously treated CNS metastases, asymptomatic and have not needed corticosteroids or anticonvulsant drugs in the 3 months prior to administering the first dose of the drug under study. Only is required CNS imaging studies (computed tomography [CT] or magnetic resonance imaging [MRI]) if clinically indicated or if the individual has a history of CNS metastases. Clinically significant gastrointestinal disorders may increase the risk of gastrointestinal bleeding including, but not limited to: Active peptic ulcer disease Known metastatic lesions with probable intraluminal bleeding Inflammatory bowel disease (ulcerative colitis, Crohn's disease) or other gastrointestinal disorders with increased risk of perforation History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days before the start of study treatment. Clinically significant gastrointestinal abnormalities may affect the absorption of the investigational product such as but not limited to: Malabsorption syndrome Major resection of the stomach or small intestine Grade 3 diarrhea Patients with active infection or other disease or serious medical condition. Prolongation of the corrected QT wave (QTc)> 480 ms on baseline ECG according to the Bazett formula. Subjects with a history of one or more of the following cardiovascular disease in the last 6 months prior to the inclusion in the study: Angioplasty or stent placement Myocardial infarction Unstable Angina Coronary bypass surgery Symptomatic peripheral vascular disease Congestive heart failure Class II, III or IV New York Heart Association (NYHA) Poorly controlled hypertension [defined as systolic blood pressure (SBP) ≥ 140 mmHg or diastolic blood pressure stress (DBP) ≥ 90 mmHg] while the patient is on antihypertensive therapy. Note: the commencement or adjustment of antihypertensive medication it is possible before the patient study start. In the baseline period measure blood pressure at least twice with a minimum interval of 24 hours. The mean values of SBP / DBP in each blood pressure reading should be <140/90 mmHg to include the subject in the study. Background, in the last six months prior to the inclusion of stroke (including transient ischemic attacks), pulmonary embolism or deep vein thrombosis (DVT) untreated. Note: may be included subjects with recent DVT who received anticoagulants for at least 6 months. Surgery or trauma in the last 28 days, or minor surgery (eg., Removal of central venous catheter) in the last 7 days prior to inclusion or unhealed wound, fracture, or ulcer. Evidence of active bleeding or bleeding diathesis. Hemoptysis within 6 weeks prior to inclusion. Pregnant or breastfeeding. Any medical condition (eg. Uncontrolled infection), psychiatric or other to be serious and / or unstable and may interfere with the safety of the patient, obtaining informed consent or compliance with study procedures.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pazopanib + interferon<br>Five levels of pazopanib in different doses: 400, 600 and 800 mg / day and interferon alfa 2-A 3, 6 and 9 MIU three times a week, in cycles of 28 days. Treatment will continue until disease progression, unacceptable toxicity, non-compliance or withdrawal of consent by the patient | Drug: Pazopanib + interferon alpha 2A<br>* Five levels of pazopanib in different doses: 400, 600 and 800 mg / day and interferon alfa 2-A 3, 6 and 9 MIU three times a week, in cycles of 28 days. Treatment will continue until disease progression, unacceptable toxicity, non-compliance or withdrawal of consent by the patient<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose (MTD) - Phase I | The MTD is defined as the dose at wich two of the patients have experienced dose-limiting toxicity. | Up to September 2012 | 
| Efficacy, response rate (Phase II) | Response rate is defined as the percentage of patients with complete response or partial response confirmed according RECIST v.1.1 | Up to July 2013 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival | Period between the start of treatment until the day in in wich the progression is confirmed by RECIST guidelines (version 1.1) or death from any cause. | Up to July 2013 | 
| Overall Survival | Period between the start of treatment and date of death from any cause. | Up to December 2013 | 
| Frequency of adverse events | Toxicity evaluation of the combination using the NCI-CTC Criteria version 3.0 | Up to July 2013 | 
| Translational Substudy | To analyze the different biomarkers and their variations with clinical outcomes of patients. | Up to December 2013 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced renal cell carcinoma, SOGUG, Pazopanib, Pazopanib in combination with interferon alpha 2A