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

Renal Cell Carcinoma Clinical Trial

Official title:

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00420888
• Other study ID #: 06762004
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: January 9, 2007
• Last updated: June 30, 2015
• Start date: January 2007
• Est. completion date: January 2013

Study information

• Verified date: June 2014
• Source: Active Biotech AB
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory AgencyRussia: Ministry of Health of the Russian FederationBulgaria: Ministry of HealthRomania: National Medicines AgencyUkraine: Ministry of Health
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 526
• Est. completion date: January 2013
• Est. primary completion date: January 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell
• Renal Cell Carcinoma

Intervention

Drug:
• ABR-217620/naptumomab estafenatox
10 mcg/kg or 15 mcg/kg, 5 minute bolus intravenous injection on 4 consecutive days / 8 week cycle repeated 3 times
• IFN-alpha
3 MIU, 6 MIU, and 9 MIU, subcutaneous or intramuscular injection 3 times / week

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Active Biotech AB

Countries where clinical trial is conducted

Bulgaria,  Romania,  Russian Federation,  Ukraine,  United Kingdom, 

References & Publications (2)

Elkord E, Burt DJ, Sundstedt A, Nordle Ö, Hedlund G, Hawkins RE. Immunological response and overall survival in a subset of advanced renal cell carcinoma patients from a randomized phase 2/3 study of naptumomab estafenatox plus IFN-a versus IFN-a. Oncotar — View Citation

Hawkins RE, Gore M, Shparyk Y, Bondar V, Gladkov O, Ganev T, Harza M, Polenkov S, Bondarenko I, Karlov P, Karyakin O, Khasanov R, Hedlund G, Forsberg G, Nordle O, Eisen T. A Randomized Phase 2/3 Study of Naptumomab Estafenatox + IFN-a vs IFN-a in Renal Ce — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to death		every 12 weeks, including after a maximum of 18 months of study treatment	No
Secondary	Progression-free survival time		every 12 weeks for the 18-month treatment period and also every 12 weeks after the treatment period	No
Secondary	Objective tumor response rate		every 12 weeks for the 18-month treatment period	No
Secondary	Best overall response		every 12 weeks for the 18-month treatment period	No
Secondary	Duration of response		every 12 weeks for the 18-month treatment period	No
Secondary	Changes in sum of target lesions		every 12 weeks for the 18-month treatment period	No
Secondary	Immunological response in patients on combined treatment of ABR-217620/naptumomab estafenatox and IFN-alpha		Weeks 1, 9, 17, 25, 73	Yes
Secondary	Vital signs		every visit through Week 25, plus Week 73	Yes
Secondary	Physical measurements		Weeks 1, 9, 17, 25, 73	Yes
Secondary	Adverse events		every visit through Week 73	Yes
Secondary	Laboratory safety assessments		Weeks 1, 2, 3, 5, 9, 10, 13, 17, 18, 21, 25, and 73	Yes
Secondary	Pharmacokinetic parameters of ABR-217620/naptumomab estafenatox		Weeks 1, 9, and 17	No