ABR-217620/Naptumomab Estafenatox With Interferon-alpha (IFN-alpha) Compared to IFN-alpha Alone in Patients With Advanced Renal Cell Carcinoma

Study Overview
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Brief Summary
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The drug ABR-217620/naptumomab estafenatox is a fusion of two proteins, one that recognizes tumor cells and one that triggers an attack on the tumor cells by activating some white blood cells belonging to the body's normal immune system. This results in an accumulation of white blood cells in the cancer that can fight the cancer. This study will compare the safety and effectiveness (assessed by tumor status and survival) of ABR-217620/naptumomab estafenatox when given with standard therapy IFN-alpha to IFN-alpha alone in patients with advanced renal cell carcinoma (RCC).

Official Title
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A Randomized, Open-label, Multi-center, Phase II/III Study on Treatment With ABR-217620/Naptumomab Estafenatox Combined With IFN-alpha vs. IFN-alpha Alone in Patients With Advanced Renal Cell Carcinoma.

Conditions
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Renal Cell Carcinoma

Intervention / Treatment
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* Drug: ABR-217620/naptumomab estafenatox
* Drug: IFN-alpha


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed RCC (clear cell and papillary types) Metastatic or inoperable locally advanced RCC Eligible for therapy with IFN-alpha. Measurable disease defined by at least 1 measurable lesion on CT scan (lesion diameter greater than or equal to 2.0 cm by a standard CT scanner or greater than or equal to 1.0 cm by a spiral CT scanner) Favorable or moderate risk group prognosis by MSKCC (Motzer) criteria (score 0-2) Karnofsky performance status greater than or equal to 70 Age greater than or equal to 18 Life expectancy greater than 3 months Baseline blood counts: Absolute neutrophil count (ANC) greater than or equal to 1.5 x 10^9/L Platelets greater than or equal to 100 x 10^9/L Haemoglobin greater than or equal to 100 g/L Baseline blood chemistry levels: Creatinine less than or equal to 1.5 x upper limit of normal (ULN) Bilirubin less than or equal to 2 x ULN Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 2.5 x ULN. AST and ALT allowed less than or equal to 5 x ULN for patients with liver metastases. If fertile, patient will use effective method of contraception throughout the study Willing and able to comply with the treatment and follow-up visits and examinations Capable of understanding the parameters in the protocol and able to sign a written consent form Exclusion Criteria: Pregnant or breastfeeding women Serious uncontrolled medical disorder or active infection ongoing or resolved within 2 weeks before first dose of study drug and that the investigator believes would impair the patient's ability to receive study drug History of malignancy within 5 years or concurrent malignancy, except successfully treated non-melanoma skin cancer, cervical cancer in situ, ductal carcinoma in situ or lobular carcinoma in situ of breast may be included History and/or signs of parenchymal brain metastases Significant cardiac disease including: history (within 6 months) or current unstable angina pectoris, congestive heart failure (NYHA stage III-IV), myocardial infarction within 12 months, or uncontrolled arterial hypertension. History of stroke within 5 years and/or transient ischemic attack within 6 months. Acute illness or evidence of infection, including unexplained fever (>100.5ºF or 38.1ºC) within 2 weeks before start of treatment Treatment with biological response modifiers within 3 weeks prior to the start of treatment and up to the End-of-Study visit Treatment with beta-blockers, including topical therapy for glaucoma, within 5 days before start of treatment and during the 4-day ABR-217620/naptumomab estafenatox treatment Treatment with systemic corticosteroids within 2 weeks before start of treatment or likely need for such treatment during the study Active autoimmune disease requiring therapy or any history of systemic lupus erythematosus or rheumatoid arthritis Known positive serology for HIV Chronic hepatitis with advanced, decompensated hepatic disease or cirrhosis of the liver or history of chronic virus hepatitis or known virus carrying; patients who recovered from Hepatitis A are allowed Treatment with anticoagulants within 2 weeks before start of treatment, except when used to maintain the patency of a central or peripheral venous line Radiotherapy less than 4 weeks before start of treatment Major surgery or tumor embolization less than 4 weeks before start of treatment Previous exposure to murine monoclonal antibodies or known hypersensitivity to murine proteins Currently on renal dialysis treatment Known allergy or hypersensitivity to aminoglycosides and kanamycin Previous systemic anti-tumor therapy for RCC (including immunotherapy with IFN-alpha or IL-2 or any chemotherapy) except sunitinib or other oral antiangiogenic therapy Participation in any study with investigational drugs for RCC within 6 weeks

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Safety group<br>6-12 patients | Drug: ABR-217620/naptumomab estafenatox<br>* 10 mcg/kg or 15 mcg/kg, 5 minute bolus intravenous injection on 4 consecutive days / 8 week cycle repeated 3 times<br>* Other names: naptumomab estafenatox;Drug: IFN-alpha<br>* 3 MIU, 6 MIU, and 9 MIU, subcutaneous or intramuscular injection 3 times / week<br>* Other names: Referon-A;|
| Experimental: 1<br> | Drug: ABR-217620/naptumomab estafenatox<br>* 10 mcg/kg or 15 mcg/kg, 5 minute bolus intravenous injection on 4 consecutive days / 8 week cycle repeated 3 times<br>* Other names: naptumomab estafenatox;Drug: IFN-alpha<br>* 3 MIU, 6 MIU, and 9 MIU, subcutaneous or intramuscular injection 3 times / week<br>* Other names: Referon-A;|
| Other: 2<br>Standard treatment with IFN-alpha without add-on of ABR-217620/naptumomab estafenatox | Drug: IFN-alpha<br>* 3 MIU, 6 MIU, and 9 MIU, subcutaneous or intramuscular injection 3 times / week<br>* Other names: Referon-A;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to death |  | every 12 weeks, including after a maximum of 18 months of study treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival time |  | every 12 weeks for the 18-month treatment period and also every 12 weeks after the treatment period | 
| Objective tumor response rate |  | every 12 weeks for the 18-month treatment period | 
| Best overall response |  | every 12 weeks for the 18-month treatment period | 
| Duration of response |  | every 12 weeks for the 18-month treatment period | 
| Changes in sum of target lesions |  | every 12 weeks for the 18-month treatment period | 
| Immunological response in patients on combined treatment of ABR-217620/naptumomab estafenatox and IFN-alpha |  | Weeks 1, 9, 17, 25, 73 | 
| Vital signs |  | every visit through Week 25, plus Week 73 | 
| Physical measurements |  | Weeks 1, 9, 17, 25, 73 | 
| Adverse events |  | every visit through Week 73 | 
| Laboratory safety assessments |  | Weeks 1, 2, 3, 5, 9, 10, 13, 17, 18, 21, 25, and 73 | 
| Pharmacokinetic parameters of ABR-217620/naptumomab estafenatox |  | Weeks 1, 9, and 17 |