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 has been completed.
Sponsor:
Information provided by (Responsible Party):
immatics Biotechnologies GmbH
ClinicalTrials.gov Identifier:
NCT00785122
First received: November 4, 2008
Last updated: May 15, 2013
Last verified: May 2013
  Purpose

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Patients in the 1st and 2nd cohort will be withdrawn from study treatment once a progress according to RECIST is noted.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.


Condition Intervention Phase
Colorectal Carcinoma
Drug: Endoxana, Leukine, IMA910
Drug: Endoxana, Leukine, IMA910, Aldara
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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 [ Time Frame: continuously ] [ Designated as safety issue: Yes ]
    Safety assessment with special emphasis on the inclusion of the first 6 patients enrolled according to a pre-specified enrolment plan


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 [ Time Frame: till End of Study ] [ Designated as safety issue: No ]
  • Progression free survival [ Time Frame: until tumor progression or death ] [ Designated as safety issue: No ]
  • Cellular immunomonitoring [ Time Frame: till 27 weeks of vaccination or End Of Study ] [ Designated as safety issue: No ]
    • T-cell responses to peptides contained in IMA910

      • Description of T-cell responses
      • Percentage of multipeptide responders
      • Number of TUMAPs to which a response can be detected in multipeptide responders
    • Other immune cell populations that may influence T-cell responses such as regulatory T cells

  • Biomarkers [ Time Frame: Pre-Vaccination and End of Study ] [ Designated as safety issue: No ]
    Pre-vaccination and post-vaccination analysis of serum markers with suspected influence on success of vaccination such as cytokines.

  • Analysis of tumor tissue [ Time Frame: optional if available ] [ Designated as safety issue: No ]

    Depending on the amount, type & quality parameters may be assessed:

    • Analysis of expression of tumor genes influencing immune response
    • Presentation of TUMAPs contained in IMA910
    • Tumor infiltrating lymphocytes and other immune cell populations
    • Presence of molecules with suspected influence on immune response
    • Alteration in the tumor signature under the influence of study treatment with respect to expression of the target genes encoding the TUMAPs contained in IMA910 and all the above mentioned parameters

  • Overall Safety [ Time Frame: continuously till End of Study ] [ Designated as safety issue: Yes ]
  • Effect of imiquimod (2nd Cohort) on immune response [ Time Frame: till End of Study ] [ Designated as safety issue: No ]

    All effectiveness and immunological endpoints will be analysed separately for the

    1st and the 2nd cohort. Overall safety, biomarkers and analysis of tumour tissue will be analysed separately for the 1st and the 2nd cohort and additionally overall for both cohorts.


  • Overall survival [ Time Frame: unitl death ] [ Designated as safety issue: No ]
  • Non-Cellular immunomonitoring [ Time Frame: till 27 weeks of vaccination ] [ Designated as safety issue: No ]
    • Serum levels of antibodies directed against peptides contained in IMA910 and against MHC/peptide complexes thereof
    • Presence of molecules with suspected influence on immune response such as serum TGFβ


Enrollment: 92
Study Start Date: June 2008
Study Completion Date: May 2013
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Endoxana, Leukine, IMA910
    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
    Other Names:
    • Endoxana (Cyclophosphamide)
    • Aldara (Imiquimod)
    • IMA910
    • GM-CSF
    Drug: Endoxana, Leukine, IMA910, Aldara
    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)
    Other Names:
    • Endoxana (Cyclophosphamide)
    • Aldara (Imiquimod)
    • IMA910
    • GM-CSF
  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 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

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 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:

    • 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
    • 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)
    • 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:

    • Heart failure or non-compensated active heart disease (=NYHA Class III and IV)
    • Severe coronary heart disease, cardiac arrhythmia requiring medication, or uncontrolled hypertension
    • Symptomatic neurotoxicity (motor or sensory) = Grade 3 according to Common Terminology Criteria for Adverse Events v3.0 (CTCAE)
    • 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00785122

  Show 41 Study Locations
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
ClinicalTrials.gov Identifier: NCT00785122     History of Changes
Other Study ID Numbers: EudraCT Nr. 2007-005666-12
Study First Received: November 4, 2008
Last Updated: May 15, 2013
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products
Bulgaria: Bulgarian Drug Agency
Germany: Paul-Ehrlich-Institut
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 and Montenegro: Agency for Drugs and Medicinal Devices
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by immatics Biotechnologies GmbH:
cancer vaccine

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

ClinicalTrials.gov processed this record on August 20, 2014