MedPath

IMA901 in Patients Receiving Sunitinib for Advanced/Metastatic Renal Cell Carcinoma

Phase 3
Completed
Conditions
Metastatic Renal Cell Carcinoma
Interventions
Registration Number
NCT01265901
Lead Sponsor
Immatics Biotechnologies GmbH
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
339
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
IMA901 plus GM-CSF added to sunitinib after single dose of cyGM-CSFAfter 1 cycle of sunitinib, intradermal vaccinations with IMA901 plus GM-CSF as adjuvant after a single dose of cyclophosphamide will be applied for a period of 4 months while continuing treatment with sunitinib
SunitinibSunitinibSunitib as Standard therapy per Label.
IMA901 plus GM-CSF added to sunitinib after single dose of cySunitinibAfter 1 cycle of sunitinib, intradermal vaccinations with IMA901 plus GM-CSF as adjuvant after a single dose of cyclophosphamide will be applied for a period of 4 months while continuing treatment with sunitinib
IMA901 plus GM-CSF added to sunitinib after single dose of cyCyclophosphamideAfter 1 cycle of sunitinib, intradermal vaccinations with IMA901 plus GM-CSF as adjuvant after a single dose of cyclophosphamide will be applied for a period of 4 months while continuing treatment with sunitinib
IMA901 plus GM-CSF added to sunitinib after single dose of cyIMA901After 1 cycle of sunitinib, intradermal vaccinations with IMA901 plus GM-CSF as adjuvant after a single dose of cyclophosphamide will be applied for a period of 4 months while continuing treatment with sunitinib
Primary Outcome Measures
NameTimeMethod
Overall survival2015 (estimated)
Secondary Outcome Measures
NameTimeMethod
Overall survival in biomarker-defined subgroup2015 (estimated)
Best tumor response2014 (estimated)
Progression-free survival2014 (estimated)
Safety and tolerabilitycontinuously
Cellular immunomonitoring2014 (estimated)

Trial Locations

Locations (105)

Medisprof SRL

🇷🇴

Cluj-Napoca, Romania

Georgetown University Medical Center, Lombardi Comprehensive Cancer Center

🇺🇸

Washington, D.C., District of Columbia, United States

University of Arkansas for Medical Sciences

🇺🇸

Little Rock, Arkansas, United States

Hôpital Saint André

🇫🇷

Bordeaux, France

North Central Cancer Treatment Group, Illinois Cancer Care

🇺🇸

Peoria, Illinois, United States

Semmelweis University, Urology Clinic

🇭🇺

Budapest, Hungary

SC Oncolab SRL

🇷🇴

Craiova, Romania

Dzieciątka Jezus Clinical Hospital of Medical University, General Urology and Oncology Clinic

🇵🇱

Warsaw, Poland

Targu-Mures Clinical County Hospital, Oncology and Radiotherapy Department

🇷🇴

Targu-Mures, Romania

State Budget Institution of Ryazan Region "Regional Clinical Oncological Diespensary"

🇷🇺

Ryazan, Russian Federation

Oxford Cancer and Haematology Centre, University of Oxford, The Churchill Hospital, Oxford Radcliffe Hospital NHS Trust, Dept.of Medical Oncology

🇬🇧

Oxford, United Kingdom

State Institution "City Clinical Hospital NO20"

🇷🇺

Moscow, Russian Federation

Urology and Urological Oncology Department and Clinic

🇵🇱

Warsaw, Poland

"Prof. Dr. Ioan Chiricuta" Oncology Institute

🇷🇴

Cluj-Napoca, Romania

Saint-Petersburg Clinical Scientific and Practical Centre of Special Methods of Medical Aid (Oncology)

🇷🇺

St. Petersburg, Russian Federation

Leeds Institute of Molecular Medicine, Section of Oncology and Clinical Research, St. James's University Hospital

🇬🇧

Leeds, United Kingdom

Paterson Institute for Cancer Research, Christie Hospital NHS Foundation Trust, Medical Oncology

🇬🇧

Manchester, United Kingdom

Postgraduate Medical School, University of Surrey

🇬🇧

Surrey, United Kingdom

Federal State Institution "Russian Scientific Center of Radiology and Nuclear Medicine of Healthcare of Russian Federation"

🇷🇺

Moscow, Russian Federation

State Educational Institution of High Professional Education "Rostov State Medical University of Roszdrav"

🇷🇺

Rostov-on-Don, Russian Federation

Addenbrooke's Hospital & Peterborough District Hospital, Cambridge University Hospitals NHS Foundation Trust, Oncology Center

🇬🇧

Cambridge, United Kingdom

South West Wales Cancer Institute, Singleton Hospital, School of Medicine

🇬🇧

Swansea, United Kingdom

Royal Bournemouth Hospital

🇬🇧

Bournemouth, United Kingdom

CRUK Research Unit, Somers Cancer Research Building, Southampton General Hospital

🇬🇧

Southampton, United Kingdom

Cedars-Siani Medical Center, Samuel Oschin Comprehensive Cancer Institute

🇺🇸

Los Angeles, California, United States

The University of Chicago Medicine

🇺🇸

Chicago, Illinois, United States

IU Simon Cancer Center

🇺🇸

Indianapolis, Indiana, United States

Weinberg Cancer Institute at Franklin Hospital

🇺🇸

Baltimore, Maryland, United States

Cleveland Clinic Taussig Cancer Institute

🇺🇸

Cleveland, Ohio, United States

UPMC Cancer Pavilion, University of Pittsburgh Cancer Institute, Division of Hematology / Oncology

🇺🇸

Pittsburgh, Pennsylvania, United States

University of Cincinnati

🇺🇸

Cincinnati, Ohio, United States

Vanderbilt-Ingram Cancer Center

🇺🇸

Nashville, Tennessee, United States

Seattle Cancer Care Alliance

🇺🇸

Seattle, Washington, United States

Kaiser Permanente Oncology Hematology Clinic

🇺🇸

Denver, Colorado, United States

ROSEMERE CANCER CENTRE, Royal Preston Hospital, Lancashire Teaching Hospital

🇬🇧

Preston, United Kingdom

Klinikum rechts der Isar, Urologischen Klinik und Poliklinik, Technische Universität München

🇩🇪

Munich, Germany

Urologische Klinik Dr. Castringius, München-Planegg

🇩🇪

Planegg, Germany

Klinikum St. Elisabeth Straubing GmbH

🇩🇪

Straubing, Germany

Klinik für Urologie, Universitätsklinikum Tübingen

🇩🇪

Tübingen, Germany

Klinik für Innere Medizin III, Hämatologie - Onkologie - Rheumatologie - Infektionskrankheiten, Universitätsklinikum Ulm

🇩🇪

Ulm, Germany

Klinik und Poliklinik für Urologie, Abteilung für Operative Medizin, Universitätsklinikum Leipzig

🇩🇪

Leipzig, Germany

Urology Department, Bajcsy-Zsilinszky Hospital

🇭🇺

Budapest, Hungary

M.D. Anderson Cancer Center

🇺🇸

Orlando, Florida, United States

Karmanos Cancer Institute

🇺🇸

Detroit, Michigan, United States

Clinical Research Alliance

🇺🇸

Lake Success, New York, United States

South Texas Oncology & Hematology, P.A., The Start Center For Cancer Care

🇺🇸

San Antonio, Texas, United States

Centre Francois Baclesse, Comite Urologie-Gynecologie

🇫🇷

Caen Cedex, France

CHU Estaing, Service d'hematologie clinique adulte et de therapie cellulaire

🇫🇷

Clermont Ferrand Cedex, France

Hospital Européen Georges Pompidou, Service d'oncologie medicale

🇫🇷

Paris, France

Centre Rene Gauducheau, Service d'oncologie medicale

🇫🇷

Saint-Herblain, France

Universitätsmedizin Berlin, Charité Campus Benjamin Franklin, Urologische Klinik und Hochschulambulanz

🇩🇪

Berlin, Germany

Medizinische Klinik III für Hämatologie und Onkologie, Universitätsklinikum Bonn

🇩🇪

Bonn, Germany

Klinik für Hämatologie und internistische Onkologie, Augusta-Krankenanstalt gGmbH

🇩🇪

Bochum, Germany

Universitätsklinikum Essen, Klinik für Innere Medizin (Tumorforschung)

🇩🇪

Essen, Germany

Klinik für Hämatologie, Hämostaseologie, Onkologie und Stammzelltransplantation, Medizinische Hochschule Hannover

🇩🇪

Hannover, Germany

Nationales Centrum für Tumorerkrankungen (NCT), Medizinische Onkologie

🇩🇪

Heidelberg, Germany

Schwarzwald-Baar Klinikum Villingen-Schwenningen, Abteilung Hämatologie und Onkologie

🇩🇪

Villingen-Schwenningen, Germany

Péterfy Utcai Hospital, Urology department

🇭🇺

Budapest, Hungary

Uzsoki Utcai Hospital, Oncoradiology Center

🇭🇺

Budapest, Hungary

University of Debrecen, Faculty of Medicine, Institute of Oncology

🇭🇺

Debrecen, Hungary

University of Debrecen, Faculty of Medicine, Urology Clinic

🇭🇺

Debrecen, Hungary

Kenézy Hospital, Urology Department

🇭🇺

Debrecen, Hungary

Oncology Centre, Markhot Ferenc Training Hospital and Clinic

🇭🇺

Eger, Hungary

Pándy Kálmán County Hospital, Oncology and Radiotherapy Center

🇭🇺

Gyula, Hungary

County Oncology Centre, Hetényi Géza Hospital

🇭🇺

Szolnok, Hungary

Urology department, BAZ County Hospital

🇭🇺

Miskolc, Hungary

Urology Clinic, University of Pécs

🇭🇺

Pécs, Hungary

Oncology Therapy Clinic, University of Szeged

🇭🇺

Szeged, Hungary

Presidio Ospedaliero Ospedale San Donato, U.O. Oncologia Medica

🇮🇹

Arezzo, Italy

Oncology Department, Zala County Hospital

🇭🇺

Zalaegerszeg, Hungary

Centro di riferimento Oncologico di Aviano

🇮🇹

Aviano, Italy

Medical Oncology Unit, Policlinico Sant'Orsola Malpighi

🇮🇹

Bologna, Italy

Department of Oncology and Haematology, Division of Medical Oncology, University of Modena and Reggio Emilia

🇮🇹

Modena, Italy

Dipartimento di Oncologia, IRCCS Fondazione

🇮🇹

Pavia, Italy

Medical Oncology, Hospital Santa Maria Nuova of Reggio Emilia

🇮🇹

Reggio Emilia, Italy

Oncologia Medica, "Ospedale Infermi"

🇮🇹

Rimini, Italy

Ospedale S.S Annunziata Sasari

🇮🇹

Sassari, Italy

IRCC-Istituto di Ricerca e Cura del Cancro

🇮🇹

Torino, Italy

University Medical Center St. Radboud Centraal, Department of Urology

🇳🇱

Nijmegen, Netherlands

University Hospital, UOS - Radiumhospital

🇳🇴

Oslo, Norway

Białostockie Centrum Onkologii

🇵🇱

Białystok, Poland

Prof. Franciszek Łukaszczyk Oncology Center

🇵🇱

Bydgoszcz, Poland

Pomeranian Medical University Hospital, NZOZ Innowacyjna Medycyna

🇵🇱

Dobra, Poland

Wojewódzki Szpital Zespolony, Oncology Department

🇵🇱

Elbląg, Poland

Uniwersyteckie Centrum Kliniczne, Klinika Urologii

🇵🇱

Gdańsk, Poland

Chemotherapy Department Center of Oncology of the Lublin Region

🇵🇱

Lublin, Poland

Przemienienia Pańskiego Clinical Hospital no. 1, Oncology Clinic

🇵🇱

Poznań, Poland

Olsztyński Oncology Center "KOPERNIK"

🇵🇱

Olsztyn, Poland

Private Outpatient Clinic MRUKMED

🇵🇱

Rzeszów, Poland

Samodzielny Publiczny Szpital Kliniczny Nr 2 PUM w Szczecinie

🇵🇱

Szczecin, Poland

State Budget Institution of Healthcare "Chelyabinsk regional clinical oncological Dispensary"

🇷🇺

Chelyabinsk, Russian Federation

Republican Clinical Oncology Dispensary of Ministry of Health of Republic Tatarstan

🇷🇺

Kazan, Russian Federation

Orenburg Regional Clinical Oncological Dispensary

🇷🇺

Orenburg, Russian Federation

Saint Petersburg State Institution of Healthcare "City Clinical Oncological Dispensary"

🇷🇺

St. Petersburg, Russian Federation

Moscow Hertsen Scientific Research Oncological Institute

🇷🇺

Moscow, Russian Federation

Niepubliczny Zaklad Opieki Zdrowotnej "Magodent"

🇵🇱

Warsaw, Poland

Fundeni Clinical Institute

🇷🇴

Bucharest, Romania

Emergency Clinical County Hospital Oradea

🇷🇴

Oradea, Romania

State Institution of Healthcare "Leningrad Regional Oncological Dispensary"

🇷🇺

St. Petersburg, Russian Federation

Saint-Petersburg State Institution of Healthcare "City Universal Hospital N02"

🇷🇺

St. Petersburg, Russian Federation

Federal State Institution "Russian Scientific Center of Radiology and Surgery Technologies" of Ministry of Healthcare of Russian Federation"

🇷🇺

St. Petersburg, Russian Federation

Nonstate Institution of Healthcare "Railway clinical Hospital at Station Saratov-2 of "RZGD" PC"

🇷🇺

Saratov, Russian Federation

Federal State Institution "Scientific Research Institute of Oncology named after N.N. Petrov of Ministry of Healthcare of Russian Federation"

🇷🇺

St. Petersburg, Russian Federation

State Institution of Healthcare of Yaroslavl Region "Regional Clinical Oncological Hospital"

🇷🇺

Yaroslavl, Russian Federation

Institution of Russian Academy of Medical Science, "Russian Oncological Scientific Center named after N.N. Blokhin of Russian Academy of Medical Science"

🇷🇺

Moscow, Russian Federation

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