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IMA910 Plus GM-CSF With Low-dose Cyclophosphamide Pre-treatment in Advanced Colorectal Carcinoma Patients Following a Successful 12 Week First-line Treatment With Oxaliplatin-based Chemotherapy (IMA910-101)
This study is currently recruiting participants.
Verified by immatics Biotechnologies GmbH, December 2009
First Received: November 4, 2008   Last Updated: December 15, 2009   History of Changes
Sponsor: immatics Biotechnologies GmbH
Information provided by: immatics Biotechnologies GmbH
ClinicalTrials.gov Identifier: NCT00785122
  Purpose

This study is being conducted in order to determine whether IMA910 as single agent with GM-CSF as adjuvant following pre-treatment with low-dose cyclophosphamide is safe and shows sufficient anti-tumour effectiveness in patients with advanced CRC to warrant further development. The regular study duration for individual patients comprises regularly 3-6 weeks of screening, 33 weeks of treatment (16 vaccinations) and 4 weeks follow-up. Thus, the period between start of screening and end of study is about 10 months per patient. Patients will be withdrawn from study treatment once a progress according to RECIST is noted. An enrolment plan for the first 6 patients included in this study will be used to ensure maximum safety of the study participants.


Condition Intervention Phase
Colorectal Carcinoma
Drug: Endoxana, IMA910, Leukine
Phase I
Phase II

Study Type: Interventional
Study Design: Treatment, Open Label, Active Control, Single Group Assignment, Safety/Efficacy Study
Official Title: An Open Label, Multicenter Phase 1-2 Study to Investigate the Effectiveness, Safety and Immunogenicity of a Monotherapy With Intradermal IMA910 Plus GM-CSF Following Pre-treatment With Low-dose Cyclophosphamide in Advanced Colorectal Carcinoma Patients Who Have Successfully Completed a 12 Week First-line Treatment With Oxaliplatin-based Chemotherapy.

Resource links provided by NLM:


Further study details as provided by immatics Biotechnologies GmbH:

Primary Outcome Measures:
  • Disease control rate [ Time Frame: after 27 weeks of vaccination ] [ Designated as safety issue: No ]
  • Safety assessment of the first six enrolled patients [ Time Frame: 3 weeks after first vaccination ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Tumour response rates and SD rate [ Time Frame: after 27 and 37 weeks ] [ Designated as safety issue: No ]
  • DCR [ Time Frame: after 37 weeks on study ] [ Designated as safety issue: No ]
  • Duration of response [ Designated as safety issue: No ]
  • and OS [ Designated as safety issue: No ]
  • Cellular and non-cellular immunomonitoring [ Designated as safety issue: No ]
  • Biomarkers [ Designated as safety issue: No ]
  • Analysis of tumour tissue [ Designated as safety issue: No ]
  • Overall Safety [ Designated as safety issue: Yes ]

Estimated Enrollment: 70
Study Start Date: June 2008
Estimated Study Completion Date: April 2010
Estimated Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Endoxana, IMA910, Leukine
    a single i.v. infusion of 300 mg/m2 Cyclophosphamide and then 3 days later (visit 1) patients will start vaccination therapy with intradermal (i.d.) injections of 75µg GM-CSF followed by i.d. injections of 5.78 mg IMA90
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Aged at least 18 years
  • HLA type: HLA-A*02-positive
  • Histologically confirmed colorectal adenocarcinoma (CRC)
  • Radiological evidence (CT/MRI) of unresectable locally advanced and/or metastatic CRC prior to 12 week first-line oxaliplatin-based standard chemotherapy
  • 12 week first-line chemotherapy with an oxaliplatin-based regimen according to an established standard protocol (e.g. FOLFOX or XELOX) administered at the following minimum dosages over this 12 week period: Oxaliplatin 400 mg/m2, Fluorouracil (5FU) 10.000 mg/m2 or Capecitabine 84.000 mg/m2 (a time window for application of first-line chemotherapy of +4 weeks is allowed)
  • Response (CR, PR) or stabilization (SD) following a 12 week first-line oxaliplatin-based standard chemotherapy shown by radiological evidence (CT/MRI after last cycle of first-line oxaliplatin-based standard chemotherapy compared to CT/MRI taken before start of first-line oxaliplatin-based standard chemotherapy)
  • Patients accept a chemotherapy-free interval under close observation (CT or MRI scans performed every 9 weeks)
  • Maximum period between start of study treatment and start of the last cycle of standard chemotherapy (= first day of last cycle of standard chemotherapy) is 6 weeks; minimum period is 3 weeks
  • Karnofsky Performance Status >=80%
  • Able to understand the nature of the study and give written informed consent
  • Willing and ability to comply with the study protocol for the duration of the study

Exclusion Criteria:

  • Any adjuvant systemic or local chemotherapy if ended <=6 months before start of systemic first-line oxaliplatin-based standard chemotherapy
  • Progressive disease during or at the end of 12 week systemic first-line oxaliplatin based standard chemotherapy
  • CT/MRI scans taken more than 6 weeks before start of first-line oxaliplatin-based standard chemotherapy
  • Response to 12 week first-line oxaliplatin-based standard chemotherapy resulting in resectable disease; curative treatment intended
  • Immunosuppressive therapy within 10 days before first vaccination e.g. corticosteroid treatment (inhalative corticosteroids for e.g. asthma are allowed)
  • Radiotherapy during and/or following the 12 week first-line oxaliplatin-based standard chemotherapy (palliative radiotherapy for bone metastasis is allowed)
  • Concurrent or prior participation in a clinical trial within the last 60 days
  • History of other malignant tumours within the last 5 years, except basal cell carcinoma or curatively excised cervical carcinoma in situ
  • Presence of known brain metastasis on MRI or CT scans
  • Current partial or complete bowel obstruction
  • Patients with a history or evidence of systemic autoimmune disease
  • Any vaccination within 2 weeks before first vaccination
  • Any planned prophylactic vaccination from study entry until the end of the induction period (Week 6 after first vaccination, exception: if medically indicated)
  • Major surgery ≤4 weeks before first vaccination
  • Any of the following abnormal laboratory values:

    1. Haematology:

      Hb <9 g/dL WBC <2.5 x 109/L Neutrophils <1.5 x 109/L Lymphocytes <1.0 x 109/L Platelets <75 x 109/L

    2. Liver function:

      Serum bilirubin >1.5 x upper normal limit (unless a history of Gilbert's disease) ALAT or ASAT >3 x upper normal limit (>5 x ULN if liver metastases are present) Alkaline Phosphatase >3 x upper normal limit (>5 x ULN if liver metastases are present)

    3. Renal function: serum creatinine >200 µmol/L (2.3 mg/dL)
  • Known active hepatitis B or C infection
  • Known HIV infection
  • Active infections requiring oral or intravenous antibiotics
  • Any other infection with a biological agent that can cause a severe disease and poses a severe danger to lab personnel working on patient tissues. Examples are: rabies, Mycobacterium tuberculosis, Coccidioides immitis
  • Patients with other significant diseases currently uncontrolled by treatment which might interfere with study completion, including gastrointestinal, hepatic, renal, respiratory, cardiovascular, haematological, coagulation, metabolic or hormonal diseases with clinically relevant abnormal organ function for example:

    1. Heart failure or non-compensated active heart disease (=NYHA Class III and IV)
    2. Severe coronary heart disease, cardiac arrhythmia requiring medication, or uncontrolled hypertension
    3. Symptomatic neurotoxicity (motor or sensory) = Grade 3 according to Common Terminology Criteria for Adverse Events v3.0 (CTCAE)
    4. Severe pulmonary dysfunction
  • Psychiatric disabilities, seizures or central nervous system disorders that may interfere with the ability to give informed consent or perform adequate follow-up in the investigator's opinion
  • Pregnancy or breast-feeding
  • Hypersensitivity to the study drugs (cyclophosphamide, GM-CSF, IMA910) including excipients
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00785122

Contacts
Contact: Andrea Mayer-Mokler +49 7071 565 125 ext 18 mayer@immatics.com
Contact: Jürgen Frisch, MD +49 7071 565 125 ext 13 frisch@immatics.com

Locations
Belgium
Oncologisch Centrum, UZ Gent Recruiting
Gent, Belgium, 9000
Contact: Tine Derre     +32/93325125     tine.derre@ugent.be    
Principal Investigator: Marc Peeters, Prof. Dr.            
Medische Oncologie, Imeldaziekenhuis Not yet recruiting
Bonheiden, Belgium, 2820
Contact: Doreen Iwens     +32/15504712     Doreen.Iwens@imelda.be    
Principal Investigator: Veerle Moons, MD            
Germany
Internistische onkologische Studienzentrale Active, not recruiting
Dresden, Germany, 01307
Krankenhaus Nordwest der Stiftung Hospital zum heiligen Geist, II. med. Klinik Active, not recruiting
Frankfurt a.M., Germany, 60488
University of Tübingen, Department of med. Oncology, Hematology, Immunology, Rhematology and Pulmology Recruiting
Tübingen, Germany, 72076
Contact: Corinna Jäth     +49/7071-29-80611     corinna.jaeth@med.uni-tuebingen.de    
Principal Investigator: Frank Mayer, PD Dr. Dr.            
Universitätsklinikum Ulm, Dep. Of Internal Medicine I, Studiensekretariat, CCCU, CTOA Recruiting
Ulm, Germany, 89081
Contact: Yvonne Kriebisch     +49/731-500-44764     ivonne.kriebisch@uniklinik-ulm.de    
Principal Investigator: Götz von Wichert, PD Dr.            
Kliniken Villingen, Schwarzwald-Baar-Klinik, Dept. Of Hematology & Oncology Recruiting
Villingen-Schwenningen, Germany, 78050
Contact: Yasmin Hoffmann     +49/7721-93-4022     yasmin.hoffmann@sbk.vs.de    
Principal Investigator: Wolfram Brugger, Prof. Dr.            
Prosper-Hospital, Med. Klinik I Recruiting
Recklinghausen, Germany, 45659
Contact: Annette Schröder     +49/23-61-54-15029     annette.schroeder@prosper-hospital.de    
Principal Investigator: Thomas Höhler, Prof. Dr.            
Medical School Hannover, MHH, Gastroenterologie Recruiting
Hannover, Germany, 30625
Contact: Monique Hörning     +49/511-532-6779     hoerning.monique@mh-hannover.de    
Principal Investigator: Stefan Kubicka, Prof. Dr.            
Hungary
National Institute of Oncology, Department of Internal Medicine, Department of Chemotherapy "B" Recruiting
Budapest, Hungary, 1122
Contact: Erika Hitre, MD     +36/30-430-15-13     hitre@oncol.hu    
Contact: Atila Kiss            
Principal Investigator: Istvan Lang, MD            
Állami Egészségügyi Központ (volt MÀV Kórház), Dept. of Oncology Not yet recruiting
Budapest, Hungary, 1062
Contact: Geza Lakner, MD            
Principal Investigator: Geza Lakner, MD            
Uszoki Hospital Not yet recruiting
Budapest, Hungary, 1145
Contact: Màrta Baki, MD            
Principal Investigator: Màrta Baki, MD            
Semmelweis University, Oncoradiology Recruiting
Budapest, Hungary, 1085
Contact: Edit Pthö     +36/208-258-824     dank@radi.sote.hu    
Principal Investigator: Magdolna Dank            
Péterfy Hospital Recruiting
Budapest, Hungary, 1076
Contact: Tamas Magyar, MD            
Principal Investigator: Tamas Magyar, MD            
University of Szeged, Department of Oncotherapy Recruiting
Szeged, Hungary, 6720
Contact: Zita Ferenczi     +36/62-544-984     ferenczi@onko.szote.u-szeged.hu    
Principal Investigator: László Thurzo, MD            
Latvia
Pauls Stradins University Hospital Recruiting
Riga, Latvia, 1002
Contact: Aiga Gaile            
Principal Investigator: Gunta Purkalne, Prof. Dr.            
Latvia oncological Center Recruiting
Riga, Latvia, 1079
Contact: Marina Vudmaska            
Principal Investigator: Zanete Zvirbule, Prof. Dr.            
Poland
SPZOZ Szpital Uniwersytecki w Krakowie, Oddzial Kliniczny Kliniki Onkologii Not yet recruiting
Krakow, Poland, 31-501
Contact: Joanna Huszno            
Principal Investigator: Janusz Pawlega, Prof. Dr.            
Klinika Chemioterapii Nowotworów, Regionalny Ośrodek Onkologiczny, Wojewódzki Szpital Specjalistyczny im. M.Kopernika Uniwersytetu Medycznego Łódz Not yet recruiting
Lodz, Poland, 93-509
Contact: Anna Pluszanska, Prof. Dr.            
Principal Investigator: Anna Pluszanska, Prof. Dr.            
Katedra i Klinika Hematologii, Onkologii i Cherob Wewnetrznych AM SP Centralny Szpital Kliniczny w Warszawie Recruiting
Warszawa, Poland, 02-097
Contact: Anna Swieboda, MD            
Principal Investigator: Wieslaw Wiktor Jedrzejzczak, Prof. Dr.            
Serbia
Institute for Oncology and Radiology of Serbia, National Cancer Research Center, Clinical Research and Exp. Pharmacology Recruiting
Belgrade, Serbia, 11000
Contact: Zorika Marinkovic            
Principal Investigator: Sinisa Radulovic, Prof. Dr.            
Oncology Institute of Vojvodina Recruiting
Sremska, Serbia, 21204
Contact: Ivan Nikolic, MD     +381/214-805-569     nikolic.ivan@onko.onk.ns.ac.yu    
Principal Investigator: Dusan Jovanovic, Prof. Dr.            
Sponsors and Collaborators
immatics Biotechnologies GmbH
Investigators
Study Director: Andrea Mayer-Mokler immatics biotechnolgies GmbH
  More Information

No publications provided

Responsible Party: immatics biotechnologies GmbH ( Andrea Mayer-Mokler )
Study ID Numbers: EudraCT Nr. 2007-005666-12
Study First Received: November 4, 2008
Last Updated: December 15, 2009
ClinicalTrials.gov Identifier: NCT00785122     History of Changes
Health Authority: Germany: Paul-Ehrlich-Institut;   Belgium: Federal Agency for Medicines and Health Products;   Hungary: National Institute of Pharmacy;   Latvia: State Agency of Medicines;   Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products;   Romania: State Institute for Drug Control;   Serbia: Agency for Medicines and Medical Devices;   United Kingdom: Medicines and Healthcare Products Regulatory Agency

Additional relevant MeSH terms:
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Gastrointestinal Diseases
Colonic Diseases
Physiological Effects of Drugs
Cyclophosphamide
Rectal Diseases
Oxaliplatin
Neoplasms by Site
Therapeutic Uses
Alkylating Agents
Digestive System Neoplasms
Neoplasms by Histologic Type
Intestinal Diseases
Immunosuppressive Agents
Intestinal Neoplasms
Pharmacologic Actions
Carcinoma
Neoplasms
Digestive System Diseases
Myeloablative Agonists
Gastrointestinal Neoplasms
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Colorectal Neoplasms
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on February 08, 2010