Clinical trial NCT00420888: ABR-217620/Naptumomab Estafenatox With Interferon-alpha (IFN-alpha) Compared to IFN-alpha Alone in Patients With Advanced Renal Cell Carcinoma
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Renal Cell Carcinoma
Lead sponsor: Active Biotech AB
Sponsor class: INDUSTRY
First posted: 2007-01-11
Enrollment: 526
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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

Primary outcomes:
measure: Time to death
timeFrame: every 12 weeks, including after a maximum of 18 months of study treatment
Secondary outcomes:
measure: Progression-free survival time
timeFrame: every 12 weeks for the 18-month treatment period and also every 12 weeks after the treatment period
measure: Objective tumor response rate
timeFrame: every 12 weeks for the 18-month treatment period
measure: Best overall response
timeFrame: every 12 weeks for the 18-month treatment period
measure: Duration of response
timeFrame: every 12 weeks for the 18-month treatment period
measure: Changes in sum of target lesions
timeFrame: every 12 weeks for the 18-month treatment period
measure: Immunological response in patients on combined treatment of ABR-217620/naptumomab estafenatox and IFN-alpha
timeFrame: Weeks 1, 9, 17, 25, 73
measure: Vital signs
timeFrame: every visit through Week 25, plus Week 73
measure: Physical measurements
timeFrame: Weeks 1, 9, 17, 25, 73
measure: Adverse events
timeFrame: every visit through Week 73
measure: Laboratory safety assessments
timeFrame: Weeks 1, 2, 3, 5, 9, 10, 13, 17, 18, 21, 25, and 73
measure: Pharmacokinetic parameters of ABR-217620/naptumomab estafenatox
timeFrame: Weeks 1, 9, and 17
Other outcomes:
Locations:
city: Pleven
country: Bulgaria
facility: Department of Chemotherapy, University General Hospital for Active Treatment "Georgi Stranski"
city: Plovdiv
country: Bulgaria
facility: 1st Internal Department District Dispensary for Cancer Diseases with Inpatient Hospital
city: Sofia
country: Bulgaria
facility: Multifile Hospital "Aleksandrovska", Urology Clinic, Department of Oncourology
city: Sofia
country: Bulgaria
facility: Oncology Clinic, University General Hospital for Active Treatment "Tzaritza Yoanna"
city: Varna
country: Bulgaria
facility: Urology Clinic, General Hospital for Active Treatment "St. Anna"
city: Veliko Tarnovo
country: Bulgaria
facility: Department of Chemotherapy, Inter-district Dispensary for Cancer Diseases with Inpatient Hospital
city: Bucharest
country: Romania
facility: Fundeni Clinical Institute - Urology Department
city: Bucharest
country: Romania
facility: Dinu Uromedica
city: Bucharest
country: Romania
facility: "Prof. Dr. Th. Burghele" Clinical Hospital, Urology Clinic
city: Cluj Napoca
country: Romania
facility: "I. Chiricuta" Institute of Oncology
city: Cluj Napoca
country: Romania
facility: E-URO Medical Center
city: Constanta
country: Romania
facility: Provita Center SRL
city: Sibiu
country: Romania
facility: Sibiu Clinical Country Hospital - Urology Clinic
city: Timisoara
country: Romania
facility: Oncomed SRL
city: Arkhangelsk
country: Russian Federation
facility: Arkhangelsk Regional Oncology Center
city: Chelyabinsk
country: Russian Federation
facility: Chelyabinsk Regional Oncology Center
city: Kazan
country: Russian Federation
facility: Republican Clinical Oncology Center
city: Kazan
country: Russian Federation
facility: Kazan City Oncology Center
city: Moscow
country: Russian Federation
facility: Research Institute of Urology
city: Moscow
country: Russian Federation
facility: Russian Oncological Research Center n.a. N.N. Blokhin
city: Moscow
country: Russian Federation
facility: Russian Research Center of Radiology
city: Obninsk
country: Russian Federation
facility: Medical Radiology Research Center
city: Orenburg
country: Russian Federation
facility: Orenburg Regional Clinical Oncology Center
city: St. Petersburg
country: Russian Federation
facility: Leningrad Regional Oncological Center
city: St. Petersburg
country: Russian Federation
facility: Municipal Aleksandrovskaya Hospital
city: St. Petersburg
country: Russian Federation
facility: Municipal Multi-Speciality Hospital #2
city: St. Petersburg
country: Russian Federation
facility: Municipal Hospital #26
city: St. Petersburg
country: Russian Federation
facility: Municipal Clinical Oncology Center
city: St. Petersburg
country: Russian Federation
facility: Central Research Institute of Roentgenology and Radiology
city: St. Petersburg
country: Russian Federation
facility: Research Institute of Oncology n.a. Professor N.N. Petrov
city: St. Petersburg
country: Russian Federation
facility: Municipal Hospital #15
city: Stavropol
country: Russian Federation
facility: Stavropol Territorial Clinical Oncology Center
city: Yaroslavl
country: Russian Federation
facility: Regional Clinical Oncology Hospital
city: Cherkassy
country: Ukraine
facility: Cherkassy Regional Oncology Center
city: Chernigov
country: Ukraine
facility: Chernigov Regional Oncology Center
city: Dnepropetrovsk
country: Ukraine
facility: Urology Department, Dnepropetrovsk State Medical Academy
city: Dnepropetrovsk
country: Ukraine
facility: City General Hospital #4
city: Donetsk
country: Ukraine
facility: Donetsk Regional Antitumor Center
city: Ivano-Frankovsk
country: Ukraine
facility: Ivano-Frankovsk Regional Oncology Center
city: Kharkiv
country: Ukraine
facility: Kharkiv Regional Urology and Nephrology Center
city: Kiev
country: Ukraine
facility: Institute of Urology under the Academy of Medical Sciences of Ukraine, Department of Plastic and Supportive Urology
city: Kiev
country: Ukraine
facility: Institute of Urology under the Academy of Medical Sciences of Ukraine, Urology Department
city: Lvov
country: Ukraine
facility: State Regional Diagnostics and Treatment Oncology Center
city: Uzhorod
country: Ukraine
facility: Regional Oncology Center
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital, Cambridge Clinical Trials Centre
city: Derby
country: United Kingdom
facility: Derby Hospital NHS Trust
city: Glasgow
country: United Kingdom
facility: The Beatson West of Scotland Cancer Centre
city: Leeds
country: United Kingdom
facility: St. James's Institute of Oncology
city: London
country: United Kingdom
facility: The Royal Marsden NHS Trust
city: Manchester
country: United Kingdom
facility: The Christie Hospital NHS Trust
city: Swansea
country: United Kingdom
facility: South Wales Cancer Institute, Singleton Hospital
Study officials:
affiliation: Active Biotech AB
name: Thore Nederman, PhD
role: STUDY_DIRECTOR
References:
citation: Hawkins R, 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 Ö, Eisen T. A randomized phase 2/3 study of naptumomab estafenatox plus IFN-α vs IFN-α in advanced renal cell carcinoma. ASCO Annual Meeting 2013; Abstract ID: 3073.
citation: Eisen T, Hedlund G, Forsberg G, Nordle Ö, Hawkins R. Baseline biomarker trend analysis of a randomized phase 2/3 study of naptumomab estafenatox plus IFN-α vs IFN-α in advanced renal cell carcinoma. European Cancer Congress (ECCO) 2013; Abstract ID: 2710.
citation: Elkord E, Burt DJ, Sundstedt A, Nordle O, 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-alpha versus IFN-alpha. Oncotarget. 2015 Feb 28;6(6):4428-39. doi: 10.18632/oncotarget.2922.