Clinical trial NCT01265901: IMA901 in Patients Receiving Sunitinib for Advanced/Metastatic Renal Cell Carcinoma
Official title: A Randomized, Controlled Phase III Study Investigating IMA901 Multipeptide Cancer Vaccine in Patients Receiving Sunitinib as First-line Therapy for Advanced/Metastatic Renal Cell Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Metastatic Renal Cell Carcinoma
Keywords: Metastatic Renal Cell Carcinoma
First line
Eligible for sunitinib
Lead sponsor: Immatics Biotechnologies GmbH
Sponsor class: INDUSTRY
First posted: 2010-12-23
Enrollment: 339
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 primary objective of the phase III study is to investigate whether IMA901 can prolong overall survival in patients with metastatic and/or locally advanced renal cell carcinoma (RCC) when added to standard first-line therapy with sunitinib.

Secondary objectives include a subgroup analysis of overall survival in patients defined by a certain biomarker signature, the investigation of progression-free survival, best tumor response, safety, and immunological parameters.

Detailed description: This is a multicenter, open-label, randomized phase III study to investigate whether therapeutic vaccination with IMA901, a mult-peptide cancer vaccine (TUMAP), can prolong overall survival in patients with metastatic and/or locally advanced RCC when added to standard first-line therapy with sunitinib (primary endpoint).

Secondary endpoints include a subgroup analysis of overall survival in patients who are positive for a prospectively defined primary biomarker signature (identified as being predictive for improved clinical outcome in IMA901-vaccinated patients in the previous phase II study), progression-free survival (PFS), best overall response, cellular immunomonitoring in a subset of patients, and safety. Safety analysis will be based on adverse events (AEs), physical examinations, vital signs, hematology, clinical chemistry, urinalysis and ECG changes.

Further endpoints include subgroup analyses of overall survival in patients who are positive for further prospectively defined biomarkers (identified in the previous phase II study), and exploratory screening of new biomarkers (to be investigated in patients' blood and paraffin sections from tumor tissue) to predict better clinical outcome as response to vaccination with IMA901. Biomarker sets will not be used for patient selection in this study.

Eligibility criteria: Inclusion Criteria:

1. Aged at least 18 years.
2. HLA type: HLA-A\*02-positive
3. Metastatic and/or locally advanced RCC with clear cell histology (histological confirmation by local pathologist required). NOTE: prior nephrectomy is NOT required.
4. Measurable and/or non-measurable tumor lesions as per RECIST 1.1
5. Patients who are candidates for a first-line therapy with sunitinib.
6. Favorable or intermediate risk according to the 6-score risk criteria in patients treated with VEGF-targeted agents according to Heng \[Heng et al. 2009\]. The patient has a favorable risk if none, or intermediate risk if one or two of the following criteria apply (if three or more criteria apply the patient is not eligible):

   1. Hemoglobin \< LLN,
   2. Serum corrected calcium \> ULN,
   3. Karnofsky performance status \< 80%,
   4. Time from initial diagnosis to initiation of therapy \< 1 year,
   5. Absolute neutrophil count \> ULN,
   6. Platelets \> ULN.
7. Able to understand the nature of the study and give written informed consent.
8. Willingness and ability to comply with the study protocol for the duration of the study.
9. Female patients who are post menopausal (no menstrual period for a minimum of 1 year), or surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy) or practice a medically acceptable method of birth control.
10. Male patients willing to use contraception (upon study entry and during the course of the study or have undergone vasectomy.

Exclusion Criteria:

1. Prior systemic therapy for metastatic disease. (Note: prior adjuvant treatment for non-metastatic disease is allowed, however adjuvant therapy must have been stopped ≥ 1 year before Visit C).
2. History of or current brain metastases.
3. Abnormal ≥ CTC Grade 3 laboratory values for hematology (Hb, WBC, neutrophils, lymphocytes, platelets), liver (serum bilirubin, ALAT or ASAT) and renal function (serum creatinine).
4. Metastatic second malignancy.
5. Localized second malignancy expected to influence the patient's life span.
6. Patients with a history or evidence of systemic autoimmune disease, e.g., rheumatoid arthritis, multiple sclerosis, systemic lupus erythematodes (SLE), scleroderma, Sjögren's syndrome, Wegener's granulomatosis, Guillain-Barre syndrome.
7. Known active hepatitis B or C infection.
8. Known HIV infection.
9. Active infections requiring oral or intravenous antibiotics.
10. Any other known infection with a biological agent that can cause a severe disease and poses a severe danger to lab personnel working on patients' blood or tissue.
11. Received study drug within any clinical study (including approved and experimental drugs) within 4 weeks before sunitinib start.
12. Serious intercurrent illness, which according to the investigator, poses an undue risk for the patient when participating in the trial, including, but not limited to, any of the following:

    * Clinically significant cardiovascular disease (e.g., uncontrolled hypertension; clinically significant cardiac arrhythmia, clinically significant QT-prolongation),
    * New York Heart Association class III-IV congestive heart failure,
    * Symptomatic peripheral vascular disease,
    * Severe pulmonary dysfunction,
    * Psychiatric illness or social situation that would preclude study compliance.
13. Less than 12 months since any of the following:

    * Myocardial infarction,
    * Severe or unstable angina,
    * Coronary or peripheral artery bypass graft,
    * Cerebrovascular event incl. transient ischemic attack,
    * Pulmonary embolism / deep vein thrombosis (DVT).
14. Pregnancy or breastfeeding.
15. Any condition which in the judgment of the investigator would place the patient at undue risk or interfere with the results of the study.

Primary outcomes:
measure: Overall survival
timeFrame: 2015 (estimated)
Secondary outcomes:
measure: Overall survival in biomarker-defined subgroup
timeFrame: 2015 (estimated)
measure: Progression-free survival
timeFrame: 2014 (estimated)
measure: Best tumor response
timeFrame: 2014 (estimated)
measure: Safety and tolerability
timeFrame: continuously
measure: Cellular immunomonitoring
timeFrame: 2014 (estimated)
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Los Angeles
country: United States
facility: Cedars-Siani Medical Center, Samuel Oschin Comprehensive Cancer Institute
state: California
city: Denver
country: United States
facility: Kaiser Permanente Oncology Hematology Clinic
state: Colorado
city: Washington, D.C.
country: United States
facility: Georgetown University Medical Center, Lombardi Comprehensive Cancer Center
state: District of Columbia
city: Orlando
country: United States
facility: M.D. Anderson Cancer Center
state: Florida
city: Chicago
country: United States
facility: The University of Chicago Medicine
state: Illinois
city: Peoria
country: United States
facility: North Central Cancer Treatment Group, Illinois Cancer Care
state: Illinois
city: Indianapolis
country: United States
facility: IU Simon Cancer Center
state: Indiana
city: Baltimore
country: United States
facility: Weinberg Cancer Institute at Franklin Hospital
state: Maryland
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Lake Success
country: United States
facility: Clinical Research Alliance
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Institute
state: Ohio
city: Pittsburgh
country: United States
facility: UPMC Cancer Pavilion, University of Pittsburgh Cancer Institute, Division of Hematology / Oncology
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
city: San Antonio
country: United States
facility: South Texas Oncology & Hematology, P.A., The Start Center For Cancer Care
state: Texas
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Bordeaux
country: France
facility: Hôpital Saint André
city: Caen Cedex
country: France
facility: Centre Francois Baclesse, Comite Urologie-Gynecologie
city: Clermont Ferrand Cedex
country: France
facility: CHU Estaing, Service d'hematologie clinique adulte et de therapie cellulaire
city: Paris
country: France
facility: Hospital Européen Georges Pompidou, Service d'oncologie medicale
city: Saint-Herblain
country: France
facility: Centre Rene Gauducheau, Service d'oncologie medicale
city: Berlin
country: Germany
facility: Universitätsmedizin Berlin, Charité Campus Benjamin Franklin, Urologische Klinik und Hochschulambulanz
city: Bochum
country: Germany
facility: Klinik für Hämatologie und internistische Onkologie, Augusta-Krankenanstalt gGmbH
city: Bonn
country: Germany
facility: Medizinische Klinik III für Hämatologie und Onkologie, Universitätsklinikum Bonn
city: Essen
country: Germany
facility: Universitätsklinikum Essen, Klinik für Innere Medizin (Tumorforschung)
city: Hannover
country: Germany
facility: Klinik für Hämatologie, Hämostaseologie, Onkologie und Stammzelltransplantation, Medizinische Hochschule Hannover
city: Heidelberg
country: Germany
facility: Nationales Centrum für Tumorerkrankungen (NCT), Medizinische Onkologie
city: Leipzig
country: Germany
facility: Klinik und Poliklinik für Urologie, Abteilung für Operative Medizin, Universitätsklinikum Leipzig
city: Munich
country: Germany
facility: Klinikum rechts der Isar, Urologischen Klinik und Poliklinik, Technische Universität München
city: Planegg
country: Germany
facility: Urologische Klinik Dr. Castringius, München-Planegg
city: Straubing
country: Germany
facility: Klinikum St. Elisabeth Straubing GmbH
city: Tübingen
country: Germany
facility: Klinik für Urologie, Universitätsklinikum Tübingen
city: Ulm
country: Germany
facility: Klinik für Innere Medizin III, Hämatologie - Onkologie - Rheumatologie - Infektionskrankheiten, Universitätsklinikum Ulm
city: Villingen-Schwenningen
country: Germany
facility: Schwarzwald-Baar Klinikum Villingen-Schwenningen, Abteilung Hämatologie und Onkologie
city: Budapest
country: Hungary
facility: Péterfy Utcai Hospital, Urology department
city: Budapest
country: Hungary
facility: Semmelweis University, Urology Clinic
city: Budapest
country: Hungary
facility: Urology Department, Bajcsy-Zsilinszky Hospital
city: Budapest
country: Hungary
facility: Uzsoki Utcai Hospital, Oncoradiology Center
city: Debrecen
country: Hungary
facility: University of Debrecen, Faculty of Medicine, Institute of Oncology
city: Debrecen
country: Hungary
facility: University of Debrecen, Faculty of Medicine, Urology Clinic
city: Debrecen
country: Hungary
facility: Kenézy Hospital, Urology Department
city: Eger
country: Hungary
facility: Oncology Centre, Markhot Ferenc Training Hospital and Clinic
city: Gyula
country: Hungary
facility: Pándy Kálmán County Hospital, Oncology and Radiotherapy Center
city: Miskolc
country: Hungary
facility: Urology department, BAZ County Hospital
city: Pécs
country: Hungary
facility: Urology Clinic, University of Pécs
city: Szeged
country: Hungary
facility: Oncology Therapy Clinic, University of Szeged
city: Szolnok
country: Hungary
facility: County Oncology Centre, Hetényi Géza Hospital
city: Zalaegerszeg
country: Hungary
facility: Oncology Department, Zala County Hospital
city: Arezzo
country: Italy
facility: Presidio Ospedaliero Ospedale San Donato, U.O. Oncologia Medica
city: Aviano
country: Italy
facility: Centro di riferimento Oncologico di Aviano
city: Bologna
country: Italy
facility: Medical Oncology Unit, Policlinico Sant'Orsola Malpighi
city: Modena
country: Italy
facility: Department of Oncology and Haematology, Division of Medical Oncology, University of Modena and Reggio Emilia
city: Pavia
country: Italy
facility: Dipartimento di Oncologia, IRCCS Fondazione
city: Reggio Emilia
country: Italy
facility: Medical Oncology, Hospital Santa Maria Nuova of Reggio Emilia
city: Rimini
country: Italy
facility: Oncologia Medica, "Ospedale Infermi"
city: Sassari
country: Italy
facility: Ospedale S.S Annunziata Sasari
city: Torino
country: Italy
facility: IRCC-Istituto di Ricerca e Cura del Cancro
city: Nijmegen
country: Netherlands
facility: University Medical Center St. Radboud Centraal, Department of Urology
city: Oslo
country: Norway
facility: University Hospital, UOS - Radiumhospital
city: Białystok
country: Poland
facility: Białostockie Centrum Onkologii
city: Bydgoszcz
country: Poland
facility: Prof. Franciszek Łukaszczyk Oncology Center
city: Dobra
country: Poland
facility: Pomeranian Medical University Hospital, NZOZ Innowacyjna Medycyna
city: Elbląg
country: Poland
facility: Wojewódzki Szpital Zespolony, Oncology Department
city: Gdańsk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne, Klinika Urologii
city: Lublin
country: Poland
facility: Chemotherapy Department Center of Oncology of the Lublin Region
city: Olsztyn
country: Poland
facility: Olsztyński Oncology Center "KOPERNIK"
city: Poznań
country: Poland
facility: Przemienienia Pańskiego Clinical Hospital no. 1, Oncology Clinic
city: Rzeszów
country: Poland
facility: Private Outpatient Clinic MRUKMED
city: Szczecin
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny Nr 2 PUM w Szczecinie
city: Warsaw
country: Poland
facility: Dzieciątka Jezus Clinical Hospital of Medical University, General Urology and Oncology Clinic
city: Warsaw
country: Poland
facility: Niepubliczny Zaklad Opieki Zdrowotnej "Magodent"
city: Warsaw
country: Poland
facility: Urology and Urological Oncology Department and Clinic
city: Bucharest
country: Romania
facility: Fundeni Clinical Institute
city: Cluj Napoca
country: Romania
facility: "Prof. Dr. Ioan Chiricuta" Oncology Institute
city: Cluj-Napoca
country: Romania
facility: "Prof. Dr. Ioan Chiricuta" Oncology Institute
city: Cluj-Napoca
country: Romania
facility: Medisprof SRL
city: Craiova
country: Romania
facility: SC Oncolab SRL
city: Oradea
country: Romania
facility: Emergency Clinical County Hospital Oradea
city: Targu-Mures
country: Romania
facility: Targu-Mures Clinical County Hospital, Oncology and Radiotherapy Department
city: Chelyabinsk
country: Russian Federation
facility: State Budget Institution of Healthcare "Chelyabinsk regional clinical oncological Dispensary"
city: Kazan
country: Russian Federation
facility: Republican Clinical Oncology Dispensary of Ministry of Health of Republic Tatarstan
city: Moscow
country: Russian Federation
facility: Institution of Russian Academy of Medical Science, "Russian Oncological Scientific Center named after N.N. Blokhin of Russian Academy of Medical Science"
city: Moscow
country: Russian Federation
facility: Federal State Institution "Russian Scientific Center of Radiology and Nuclear Medicine of Healthcare of Russian Federation"
city: Moscow
country: Russian Federation
facility: Moscow Hertsen Scientific Research Oncological Institute
city: Moscow
country: Russian Federation
facility: State Institution "City Clinical Hospital NO20"
city: Orenburg
country: Russian Federation
facility: Orenburg Regional Clinical Oncological Dispensary
city: Rostov-on-Don
country: Russian Federation
facility: State Educational Institution of High Professional Education "Rostov State Medical University of Roszdrav"
city: Ryazan
country: Russian Federation
facility: State Budget Institution of Ryazan Region "Regional Clinical Oncological Diespensary"
city: Saratov
country: Russian Federation
facility: Nonstate Institution of Healthcare "Railway clinical Hospital at Station Saratov-2 of "RZGD" PC"
city: St. Petersburg
country: Russian Federation
facility: State Institution of Healthcare "Leningrad Regional Oncological Dispensary"
city: St. Petersburg
country: Russian Federation
facility: Saint-Petersburg State Institution of Healthcare "City Universal Hospital N02"
city: St. Petersburg
country: Russian Federation
facility: Saint Petersburg State Institution of Healthcare "City Clinical Oncological Dispensary"
city: St. Petersburg
country: Russian Federation
facility: Federal State Institution "Russian Scientific Center of Radiology and Surgery Technologies" of Ministry of Healthcare of Russian Federation"
city: St. Petersburg
country: Russian Federation
facility: Federal State Institution "Scientific Research Institute of Oncology named after N.N. Petrov of Ministry of Healthcare of Russian Federation"
city: St. Petersburg
country: Russian Federation
facility: Saint-Petersburg Clinical Scientific and Practical Centre of Special Methods of Medical Aid (Oncology)
city: Yaroslavl
country: Russian Federation
facility: State Institution of Healthcare of Yaroslavl Region "Regional Clinical Oncological Hospital"
city: Bournemouth
country: United Kingdom
facility: Royal Bournemouth Hospital
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital & Peterborough District Hospital, Cambridge University Hospitals NHS Foundation Trust, Oncology Center
city: Leeds
country: United Kingdom
facility: Leeds Institute of Molecular Medicine, Section of Oncology and Clinical Research, St. James's University Hospital
city: Manchester
country: United Kingdom
facility: Paterson Institute for Cancer Research, Christie Hospital NHS Foundation Trust, Medical Oncology
city: Oxford
country: United Kingdom
facility: Oxford Cancer and Haematology Centre, University of Oxford, The Churchill Hospital, Oxford Radcliffe Hospital NHS Trust, Dept.of Medical Oncology
city: Preston
country: United Kingdom
facility: ROSEMERE CANCER CENTRE, Royal Preston Hospital, Lancashire Teaching Hospital
city: Southampton
country: United Kingdom
facility: CRUK Research Unit, Somers Cancer Research Building, Southampton General Hospital
city: Surrey
country: United Kingdom
facility: Postgraduate Medical School, University of Surrey
city: Swansea
country: United Kingdom
facility: South West Wales Cancer Institute, Singleton Hospital, School of Medicine
Study officials:
affiliation: Cleveland Clinic Taussig Cancer Institute
name: Brian Rini, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Addenbrooke's Hospital University of Cambridge, UK
name: Tim Eisen, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rini BI, Stenzl A, Zdrojowy R, Kogan M, Shkolnik M, Oudard S, Weikert S, Bracarda S, Crabb SJ, Bedke J, Ludwig J, Maurer D, Mendrzyk R, Wagner C, Mahr A, Fritsche J, Weinschenk T, Walter S, Kirner A, Singh-Jasuja H, Reinhardt C, Eisen T. IMA901, a multipeptide cancer vaccine, plus sunitinib versus sunitinib alone, as first-line therapy for advanced or metastatic renal cell carcinoma (IMPRINT): a multicentre, open-label, randomised, controlled, phase 3 trial. Lancet Oncol. 2016 Nov;17(11):1599-1611. doi: 10.1016/S1470-2045(16)30408-9. Epub 2016 Oct 3.