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

Phase 2

Completed

Conditions: Renal Cell Carcinoma

Interventions: Drug: ABR-217620/naptumomab estafenatox
Drug: IFN-alpha

Registration Number: NCT00420888

Lead Sponsor: Active Biotech AB

Brief Summary: 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).

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 526

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Safety group	IFN-alpha	6-12 patients
1	ABR-217620/naptumomab estafenatox	-
Safety group	ABR-217620/naptumomab estafenatox	6-12 patients
1	IFN-alpha	-
2	IFN-alpha	Standard treatment with IFN-alpha without add-on of ABR-217620/naptumomab estafenatox

Primary Outcome Measures

Name	Time	Method
Time to death	every 12 weeks, including after a maximum of 18 months of study treatment

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (51): Oncomed SRL
🇷🇴
Timisoara, Romania
Ivano-Frankovsk Regional Oncology Center
🇺🇦
Ivano-Frankovsk, Ukraine
E-URO Medical Center
🇷🇴
Cluj Napoca, Romania
Urology Clinic, General Hospital for Active Treatment "St. Anna"
🇧🇬
Varna, Bulgaria
Sibiu Clinical Country Hospital - Urology Clinic
🇷🇴
Sibiu, Romania
Oncology Clinic, University General Hospital for Active Treatment "Tzaritza Yoanna"
🇧🇬
Sofia, Bulgaria
Multifile Hospital "Aleksandrovska", Urology Clinic, Department of Oncourology
🇧🇬
Sofia, Bulgaria
Department of Chemotherapy, Inter-district Dispensary for Cancer Diseases with Inpatient Hospital
🇧🇬
Veliko Tarnovo, Bulgaria
Department of Chemotherapy, University General Hospital for Active Treatment "Georgi Stranski"
🇧🇬
Pleven, Bulgaria
Fundeni Clinical Institute - Urology Department
🇷🇴
Bucharest, Romania
Dinu Uromedica
🇷🇴
Bucharest, Romania
"Prof. Dr. Th. Burghele" Clinical Hospital, Urology Clinic
🇷🇴
Bucharest, Romania
Cherkassy Regional Oncology Center
🇺🇦
Cherkassy, Ukraine
Regional Clinical Oncology Hospital
🇷🇺
Yaroslavl, Russian Federation
Research Institute of Oncology n.a. Professor N.N. Petrov
🇷🇺
St. Petersburg, Russian Federation
Chernigov Regional Oncology Center
🇺🇦
Chernigov, Ukraine
Urology Department, Dnepropetrovsk State Medical Academy
🇺🇦
Dnepropetrovsk, Ukraine
1st Internal Department District Dispensary for Cancer Diseases with Inpatient Hospital
🇧🇬
Plovdiv, Bulgaria
"I. Chiricuta" Institute of Oncology
🇷🇴
Cluj Napoca, Romania
Provita Center SRL
🇷🇴
Constanta, Romania
Arkhangelsk Regional Oncology Center
🇷🇺
Arkhangelsk, Russian Federation
Chelyabinsk Regional Oncology Center
🇷🇺
Chelyabinsk, Russian Federation
Republican Clinical Oncology Center
🇷🇺
Kazan, Russian Federation
Research Institute of Urology
🇷🇺
Moscow, Russian Federation
Kazan City Oncology Center
🇷🇺
Kazan, Russian Federation
Russian Oncological Research Center n.a. N.N. Blokhin
🇷🇺
Moscow, Russian Federation
Russian Research Center of Radiology
🇷🇺
Moscow, Russian Federation
Leningrad Regional Oncological Center
🇷🇺
St. Petersburg, Russian Federation
Medical Radiology Research Center
🇷🇺
Obninsk, Russian Federation
Municipal Multi-Speciality Hospital #2
🇷🇺
St. Petersburg, Russian Federation
Municipal Clinical Oncology Center
🇷🇺
St. Petersburg, Russian Federation
Orenburg Regional Clinical Oncology Center
🇷🇺
Orenburg, Russian Federation
Municipal Aleksandrovskaya Hospital
🇷🇺
St. Petersburg, Russian Federation
Municipal Hospital #26
🇷🇺
St. Petersburg, Russian Federation
Central Research Institute of Roentgenology and Radiology
🇷🇺
St. Petersburg, Russian Federation
Municipal Hospital #15
🇷🇺
St. Petersburg, Russian Federation
Stavropol Territorial Clinical Oncology Center
🇷🇺
Stavropol, Russian Federation
City General Hospital #4
🇺🇦
Dnepropetrovsk, Ukraine
Institute of Urology under the Academy of Medical Sciences of Ukraine, Urology Department
🇺🇦
Kiev, Ukraine
Institute of Urology under the Academy of Medical Sciences of Ukraine, Department of Plastic and Supportive Urology
🇺🇦
Kiev, Ukraine
State Regional Diagnostics and Treatment Oncology Center
🇺🇦
Lvov, Ukraine
Regional Oncology Center
🇺🇦
Uzhorod, Ukraine
Derby Hospital NHS Trust
🇬🇧
Derby, United Kingdom
The Beatson West of Scotland Cancer Centre
🇬🇧
Glasgow, United Kingdom
Addenbrooke's Hospital, Cambridge Clinical Trials Centre
🇬🇧
Cambridge, United Kingdom
The Christie Hospital NHS Trust
🇬🇧
Manchester, United Kingdom
St. James's Institute of Oncology
🇬🇧
Leeds, United Kingdom
The Royal Marsden NHS Trust
🇬🇧
London, United Kingdom
South Wales Cancer Institute, Singleton Hospital
🇬🇧
Swansea, United Kingdom
Donetsk Regional Antitumor Center
🇺🇦
Donetsk, Ukraine
Kharkiv Regional Urology and Nephrology Center
🇺🇦
Kharkiv, Ukraine