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)

NCT00785122 | Completed Phase 1 DMC

• 1 other identifier: EudraCT Nr. 2007-005666-12
• Study Type: interventional
• Target: 92
• Locations: 9 countries
• Sites: 41

Brief Summary

This study is being conducted in order 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. Secondary objectives of this study are investigation of immunological parameters and additional effectiveness endpoints. Furthermore, safety, immunological parameters and effectiveness of IMA910 as single agent with GM-CSF in combination with imiquimod following pre-treatment with low-dose cyclophosphamide will be investigated in a 2nd cohort of patients. The regular study duration for individual patients in the 1st and 2nd cohort comprises regularly 18-42 days of screening (excluding HLA-typing), 33 weeks of treatment (16 vaccinations) and 4 weeks follow-up. Thus, the period between start of screening and end of trial is about 10 months per patient. Patients will be followed for response to subsequent treatments (chemotherapies with or without targeted agents) and survival every 2 months after EOS visit until death. Patients in the 1st and 2nd cohort will be withdrawn from study treatment once a progress according to RECIST is noted. An enrolment plan for the first 6 patients included into the 1st cohort will be part of this study to ensure maximum safety of the study participants. The enrollment of the first 6 patients into the 2nd cohort will also follow an enrolment plan to ensure maximum safety.

Conditions

Colorectal Carcinoma

Keywords

cancer vaccine

Outcome Measures

Primary Outcomes (2)

• Disease control rate

  after 27 weeks of vaccination

• Safety assessment

  Safety assessment with special emphasis on the inclusion of the first 6 patients enrolled according to a pre-specified enrolment plan

  continuously

Secondary Outcomes (11)

• Tumour response rates and SD rate

  after 27 and 37 weeks

• DCR

  after 37 weeks on study

• Duration of response

  till End of Study

• Progression free survival

  until tumor progression or death

• Cellular immunomonitoring

  till 27 weeks of vaccination or End Of Study

Interventions

Endoxana, Leukine, IMA910 DRUG

a single i.v. infusion of 300 mg/m2 Endoxana (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

Also known as: Endoxana (Cyclophosphamide), Aldara (Imiquimod), IMA910, GM-CSF

Endoxana, Leukine, IMA910, Aldara DRUG

a single i.v. infusion of 300 mg/m2 Endoxana (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 followed by Aldara (Imiquimod)

Also known as: Endoxana (Cyclophosphamide), Aldara (Imiquimod), IMA910, GM-CSF

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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 firstline 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 (Cyclophosphamide) and start of the last cycle of standard chemotherapy (= first day of last cycle of standard chemotherapy) is 42 days; minimum period is 18 days
• 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

You may not qualify if:

• 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 9 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 applying interventional procedures (e.g. application of investigational drugs, surgical interventions) within the last 30 days before Screening 2 = Visit B
• 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:

Sponsors & Collaborators

• Immatics Biotechnologies GmbH: lead

Study Sites (41)

Medische Oncologie, Imeldaziekenhuis

Bonheiden, 2820, Belgium

Location

Oncologisch Centrum, UZ Gent

Ghent, 9000, Belgium

Location

Inter District Dispencary for Oncology Disease with Inpatient Unit Plovdiv, First Internal Ward

Plovdiv, 4004, Bulgaria

Location

District Dispensary for Oncology Diseases with Inpatient Unit, Sofia District, Chemotherapeutic Ward

Sofia, 1233, Bulgaria

Location

MHAT "Tsaritsa Yoanna", Clinic of Oncotherapy

Sofia, 1527, Bulgaria

Location

Specialized Hospital for Active Treatment in Oncology Ltd., Clinic of Chemotherapy

Sofia, 1756, Bulgaria

Location

Interdistrict Dispensary of Oncology Diseases with Inpatient Unit "Dr. Marko Markov" - Varna

Varna, 9000, Bulgaria

Location

University Hospital Dresden "Carl Gustav Carus"

Dresden, 01307, Germany

Location

Krankenhaus Nordwest der Stiftung Hospital zum heiligen Geist, II. med. Klinik

Frankfurt a.M., 60488, Germany

Location

Cancer Hospital Sanafontis

Freiburg im Breisgau, 79111, Germany

Location

Prosper-Hospital, Med. Klinik I

Recklinghausen, 45659, Germany

Location

University of Tübingen, Department of med. Oncology, Hematology, Immunology, Rhematology and Pulmology

Tübingen, 72076, Germany

Location

Universitätsklinikum Ulm, Dep. Of Internal Medicine I, Studiensekretariat, CCCU, CTOA

Ulm, 89081, Germany

Location

Kliniken Villingen, Schwarzwald-Baar-Klinik, Dept. Of Hematology & Oncology

Villingen-Schwenningen, 78050, Germany

Location

State Health Center Oncology

Budapest, 1062, Hungary

Location

Péterfy Hospital

Budapest, 1076, Hungary

Location

Semmelweis University, Oncoradiology

Budapest, 1085, Hungary

Location

National Institute of Oncology, Department of Internal Medicine, Department of Chemotherapy "B"

Budapest, 1122, Hungary

Location

Uszoki Hospital

Budapest, 1145, Hungary

Location

Borsod County Hospital

Miskolc, 3526, Hungary

Location

University of Szeged, Department of Oncotherapy

Szeged, 6720, Hungary

Location

St. Gyorgy County Hospital

Székesfehérvár, 8000, Hungary

Location

Pauls Stradins University Hospital

Riga, 1002, Latvia

Location

Latvia oncological Center

Riga, 1079, Latvia

Location

Centrum Onkologii Instytut im. Marii Skłodowskiej-Curie Klinika Onkologii Klinicznej

Gliwice, 44-100, Poland

Location

Klinika Chemioterapii Nowotworów, Regionalny Ośrodek Onkologiczny, Wojewódzki Szpital Specjalistyczny im. M.Kopernika Uniwersytetu Medycznego Łódz

Lodz, 93-509, Poland

Location

Wojewodzki Szpital Zespolony im. Ludwika Rydygiera, Oddzial Chemiotherapii

Torun, 87100, Poland

Location

Katedra i Klinika Hematologii, Onkologii i Cherob Wewnetrznych AM SP Centralny Szpital Kliniczny w Warszawie

Warsaw, 02-097, Poland

Location

Oncology Institute "Prof. Dr. Ion Chiricuta"

Cluj-Napoca, 400015, Romania

Location

Clinical County Hospital Oradea, Oncology Clinic

Oradea, 4170167, Romania

Location

Spitalul Clinic Judetean

Târgu Mureş, 540072, Romania

Location

Institute for Oncology and Radiology of Serbia, National Cancer Research Center, Clinical Research and Exp. Pharmacology

Belgrade, 11000, Serbia

Location

Vojnomedicinska Akademija, Clinic for Gastroenterology, Military Medical Academy

Belgrade, 11000, Serbia

Location

Oncology Institute of Vojvodina

Sremska, 21204, Serbia

Location

The Royal Sussex County Hospital, CIR-Unit

Brighton, BN2 5BD, United Kingdom

Location

University of Cambridge, Department of Oncology

Cambridge, CB2 0QQ, United Kingdom

Location

Velindre Cancer Centre

Cardiff, CF14 2TL, United Kingdom

Location

St Luke's Cancer Centre, The Royal Surrey County Hospital

Guildford / Surrey, GU2 7XX, United Kingdom

Location

St. James's Hospital

Leeds, LS9 7TF, United Kingdom

Location

Leicester Royal Infirmary

Leicester, LE1 5WW, United Kingdom

Location

Churchill Hospital, Dept.of Clinical Pharmacology

Oxford, OX3 7LJ, United Kingdom

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

sargramostim; Cyclophosphamide; Imiquimod; Granulocyte-Macrophage Colony-Stimulating Factor

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Andrea Mayer-Mokler

  immatics biotechnolgies GmbH

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 4, 2008
• First Posted: November 5, 2008
• Study Start: June 1, 2008
• Primary Completion: January 1, 2011
• Study Completion: May 1, 2013
• Last Updated: May 16, 2013

Record last verified: 2013-05

Locations

BU (5); BE (2); LA (2); PL (4); RO (3); DE (7); HU (8); SE (3); GB (7)