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

Metastatic Renal Cell Carcinoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01265901
• Other study ID #: IMA901-301
• Secondary ID: 2010-022459-45
• Status: Completed
• Phase: Phase 3
• First received: December 22, 2010
• Last updated: October 4, 2017
• Start date: December 2010
• Est. completion date: July 2015

Study information

• Verified date: September 2017
• Source: immatics Biotechnologies GmbH
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 339
• Est. completion date: July 2015
• Est. primary completion date: July 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell
• Metastatic Renal Cell Carcinoma

Intervention

Drug:
• Sunitinib
As per label.

Biological:
• GM-CSF
Intradermal injection of GM-CSF as adjuvant.

Drug:
• Cyclophosphamide
One single low-dose i.v. infusion prior to the first vaccination
• IMA901
Intradermal vaccinations with IMA901 vaccine.

Locations

Country	Name	City	State
France	Hôpital Saint André	Bordeaux
France	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
Germany	Universitätsmedizin Berlin, Charité Campus Benjamin Franklin, Urologische Klinik und Hochschulambulanz	Berlin
Germany	Klinik für Hämatologie und internistische Onkologie, Augusta-Krankenanstalt gGmbH	Bochum
Germany	Medizinische Klinik III für Hämatologie und Onkologie, Universitätsklinikum Bonn	Bonn
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	Klinik und Poliklinik für Urologie, Abteilung für Operative Medizin, Universitätsklinikum Leipzig	Leipzig
Germany	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	Schwarzwald-Baar Klinikum Villingen-Schwenningen, Abteilung Hämatologie und Onkologie	Villingen-Schwenningen
Hungary	Péterfy Utcai Hospital, Urology department	Budapest
Hungary	Semmelweis University, Urology Clinic	Budapest
Hungary	Urology Department, Bajcsy-Zsilinszky Hospital	Budapest
Hungary	Uzsoki Utcai Hospital, Oncoradiology Center	Budapest
Hungary	Kenézy Hospital, Urology Department	Debrecen
Hungary	University of Debrecen, Faculty of Medicine, Institute of Oncology	Debrecen
Hungary	University of Debrecen, Faculty of Medicine, Urology Clinic	Debrecen
Hungary	Oncology Centre, Markhot Ferenc Training Hospital and Clinic	Eger
Hungary	Pándy Kálmán County Hospital, Oncology and Radiotherapy Center	Gyula
Hungary	Urology department, BAZ County Hospital	Miskolc
Hungary	Urology Clinic, University of Pécs	Pécs
Hungary	Oncology Therapy Clinic, University of Szeged	Szeged
Hungary	County Oncology Centre, Hetényi Géza Hospital	Szolnok
Hungary	Oncology Department, Zala County Hospital	Zalaegerszeg
Italy	Presidio Ospedaliero Ospedale San Donato, U.O. Oncologia Medica	Arezzo
Italy	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
Netherlands	University Medical Center St. Radboud Centraal, Department of Urology	Nijmegen
Norway	University Hospital, UOS - Radiumhospital	Oslo
Poland	Bialostockie Centrum Onkologii	Bialystok
Poland	Prof. Franciszek Lukaszczyk Oncology Center	Bydgoszcz
Poland	Pomeranian Medical University Hospital, NZOZ Innowacyjna Medycyna	Dobra
Poland	Wojewódzki Szpital Zespolony, Oncology Department	Elblag
Poland	Uniwersyteckie Centrum Kliniczne, Klinika Urologii	Gdansk
Poland	Chemotherapy Department Center of Oncology of the Lublin Region	Lublin
Poland	Olsztynski Oncology Center "KOPERNIK"	Olsztyn
Poland	Przemienienia Panskiego Clinical Hospital no. 1, Oncology Clinic	Poznan
Poland	Private Outpatient Clinic MRUKMED	Rzeszów
Poland	Samodzielny Publiczny Szpital Kliniczny Nr 2 PUM w Szczecinie	Szczecin
Poland	Dzieciatka Jezus Clinical Hospital of Medical University, General Urology and Oncology Clinic	Warsaw
Poland	Niepubliczny Zaklad Opieki Zdrowotnej "Magodent"	Warsaw
Poland	Urology and Urological Oncology Department and Clinic	Warsaw
Romania	Fundeni Clinical Institute	Bucharest
Romania	"Prof. Dr. Ioan Chiricuta" Oncology Institute	Cluj Napoca
Romania	"Prof. Dr. Ioan Chiricuta" Oncology Institute	Cluj-Napoca
Romania	Medisprof SRL	Cluj-Napoca
Romania	SC Oncolab SRL	Craiova
Romania	Emergency Clinical County Hospital Oradea	Oradea
Romania	Targu-Mures Clinical County Hospital, Oncology and Radiotherapy Department	Targu-Mures
Russian Federation	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	Federal State Institution "Russian Scientific Center of Radiology and Nuclear Medicine of Healthcare of Russian Federation"	Moscow
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	Moscow Hertsen Scientific Research Oncological Institute	Moscow
Russian Federation	State Institution "City Clinical Hospital NO20"	Moscow
Russian Federation	Orenburg Regional Clinical Oncological Dispensary	Orenburg
Russian Federation	State Educational Institution of High Professional Education "Rostov State Medical University of Roszdrav"	Rostov-on-Don
Russian Federation	State Budget Institution of Ryazan Region "Regional Clinical Oncological Diespensary"	Ryazan
Russian Federation	Nonstate Institution of Healthcare "Railway clinical Hospital at Station Saratov-2 of "RZGD" PC"	Saratov
Russian Federation	Federal State Institution "Russian Scientific Center of Radiology and Surgery Technologies" of Ministry of Healthcare of Russian Federation"	St. Petersburg
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	Saint Petersburg State Institution of Healthcare "City Clinical Oncological Dispensary"	St. Petersburg
Russian Federation	Saint-Petersburg Clinical Scientific and Practical Centre of Special Methods of Medical Aid (Oncology)	St. Petersburg
Russian Federation	Saint-Petersburg State Institution of Healthcare "City Universal Hospital N02"	St. Petersburg
Russian Federation	State Institution of Healthcare "Leningrad Regional Oncological Dispensary"	St. Petersburg
Russian Federation	State Institution of Healthcare of Yaroslavl Region "Regional Clinical Oncological Hospital"	Yaroslavl
United Kingdom	Royal Bournemouth Hospital	Bournemouth
United Kingdom	Addenbrooke's Hospital & Peterborough District Hospital, Cambridge University Hospitals NHS Foundation Trust, Oncology Center	Cambridge
United Kingdom	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	Oxford Cancer and Haematology Centre, University of Oxford, The Churchill Hospital, Oxford Radcliffe Hospital NHS Trust, Dept.of Medical Oncology	Oxford
United Kingdom	ROSEMERE CANCER CENTRE, Royal Preston Hospital, Lancashire Teaching Hospital	Preston
United Kingdom	CRUK Research Unit, Somers Cancer Research Building, Southampton General Hospital	Southampton
United Kingdom	Postgraduate Medical School, University of Surrey	Surrey
United Kingdom	South West Wales Cancer Institute, Singleton Hospital, School of Medicine	Swansea
United States	Weinberg Cancer Institute at Franklin Hospital	Baltimore	Maryland
United States	The University of Chicago Medicine	Chicago	Illinois
United States	University of Cincinnati	Cincinnati	Ohio
United States	Cleveland Clinic Taussig Cancer Institute	Cleveland	Ohio
United States	Kaiser Permanente Oncology Hematology Clinic	Denver	Colorado
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	IU Simon Cancer Center	Indianapolis	Indiana
United States	Clinical Research Alliance	Lake Success	New York
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Cedars-Siani Medical Center, Samuel Oschin Comprehensive Cancer Institute	Los Angeles	California
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee
United States	M.D. Anderson Cancer Center	Orlando	Florida
United States	North Central Cancer Treatment Group, Illinois Cancer Care	Peoria	Illinois
United States	UPMC Cancer Pavilion, University of Pittsburgh Cancer Institute, Division of Hematology / Oncology	Pittsburgh	Pennsylvania
United States	South Texas Oncology & Hematology, P.A., The Start Center For Cancer Care	San Antonio	Texas
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	Georgetown University Medical Center, Lombardi Comprehensive Cancer Center	Washington, D.C.	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
immatics Biotechnologies GmbH

Countries where clinical trial is conducted

United States,  France,  Germany,  Hungary,  Italy,  Netherlands,  Norway,  Poland,  Romania,  Russian Federation,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival		2015 (estimated)
Secondary	Overall survival in biomarker-defined subgroup		2015 (estimated)
Secondary	Progression-free survival		2014 (estimated)
Secondary	Best tumor response		2014 (estimated)
Secondary	Safety and tolerability		continuously
Secondary	Cellular immunomonitoring		2014 (estimated)