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Phase I/IIa Study of Immunization With Frameshift Peptides Administered With Montanide® ISA-51 VG in Patients With Advanced MSI-H Colorectal Cancer

Phase 1/Phase 2
18 Years
Open (Enrolling)
Colorectal Cancer

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Trial Information

Phase I/IIa Study of Immunization With Frameshift Peptides Administered With Montanide® ISA-51 VG in Patients With Advanced MSI-H Colorectal Cancer

The present study is initiated to evaluate vaccination with MSI-specific FSPs in patients
with MSI-H colorectal cancer. Specifically, the present study aims at the following

- Evaluation of potential toxicity of the FSP AIM2(-1), HT001(-1), TAF1B(-1)

- Evaluation of the immune response in patients with advanced MSI-H colorectal cancer
before vaccination and after vaccination with the FSP AIM2(-1), HT001(-1), TAF1B(-1)

In this context, the present study shall demonstrate whether application of FSP in a
vaccination approach is associated with the induction of peptide-related toxicity. Hence,
the study marks the first step towards the application of FSP in humans, as it provides
information on the safety of FSP as vaccination agents for the first time. Moreover, the
study shall provide initial information, whether vaccination with FSP can induce
FSP-specific immune responses in patients with MSI-H colorectal cancer. Thus, it shall
provide information, whether FSPs AIM2(-1), HT001(-1), and TAF1B(-1) have the potential to
elicit peptide-specific immune responses and therefore represent suitable targets for the
induction of tumor antigen-specific immune responses in patients with MSI-H tumors.

The present study marks an important milestone towards a potential application of
MSI-specific FSP as therapeutic agents in the management of patients with MSI-H tumors,
particularly patients with MSI-H colorectal cancer. Long-term goal of this approach is to
develop novel tools for (1) the palliative and/or adjuvant therapy of patients with advanced
MSI-H colorectal cancer and (2) the preventive application of FSPs in mutation carriers of
the HNPCC/Lynch syndrome.

Inclusion Criteria:

Phase I part inclusion criteria (inclusion criteria for phase IIa part will be defined
later using a study amendment):

- Histologically confirmed, surgically resected colorectal cancer of advanced stage
(UICC stage III/UICC stage IV). This comprises patients with lymph node metastases
(UICC stage III), metastasis to one distant organ (UICC IV, M1a), to more than one
distant organ, or patients with peritoneal carcinosis (UICC IV, M1b)

- Detection of high level microsatellite instability (MSI-H) in the resected tumor
sample according to the international consensus criteria (multiplex PCR of
quasi-monomorphic microsatellite markers BAT25, BAT26, CAT25), see Appendix 1.

- Prior adjuvant standard therapy (chemotherapy with 5-fluorouracil/folinic acid,
oxaliplatin, irinotecan or combinations of these) OR Prior palliative standard
therapy in the first, second and third line (chemotherapy with 5-fluorouracil,
oxaliplatin, irinotecan or combinations of these and/or treatment with anti-EGFR
antibodies cetuximab or panitumumab alone or in combination with chemotherapy) with
either complete or partial remission, stable disease, or disease progression under
therapy; OR Patient has refused adjuvant or palliative standard therapy (chemotherapy
using 5-fluorouracil, oxaliplatin, or regimens combining these).

- Expected survival of at least six months.

- Full recovery from surgery or radiation therapy

- ECOG performance status 0, 1 or 2.

- The following laboratory results:

- Neutrophil count ≥ 1.5 x 109/L

- Lymphocyte count ≥ 0.5 x 109/L

- Platelet count ≥ 100 x 109/L

- Serum bilirubin < 2mg/dL

- Male or female patients ≥ 18 years old

- Last therapy discontinued at least 4 weeks prior to vaccination.

- Patient´s written informed consent for participation in the trial

Exclusion Criteria:

- Prior treatment with FSPs AIM2(-1), HT001(-1) and TAF1B(-1)

- Clinically significant heart disease (NYHA Class IV).

- Other serious illnesses, eg, serious infections requiring antibiotics or bleeding

- History of immunodeficiency disease or autoimmune disease.

- Metastatic disease to the central nervous system for which other therapeutic options,
including radiotherapy, may be available.

- HBV, HCV or HIV positivity.

- Chemotherapy, any type of radiation therapy, or immunotherapy within 4 weeks before
study entry

- Concomitant treatment with steroids, antihistaminic drugs, or nonsteroidal
anti-inflammatory drugs (unless used in low doses for prevention of an acute
cardiovascular event or for pain control). Topical or inhalational steroids are

- Participation in any other clinical trial

- Pregnancy or lactation.

- Women of childbearing potential who are not using a medically acceptable means of

- Psychiatric or addictive disorders that may compromise the ability to give informed

- Lack of availability of a patient for immunological and clinical follow-up

- Brain metastases (symptomatic and non-symptomatic)

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:


Outcome Description:

Safety as assessed by number and severity of adverse events categorized according to CTC criteria v4.0 and the probability of the induction of immune tolerance. Immune tolerance is defined as significant and sustained decline of antigen-specific cellular immune responses after vaccination compared to the antigen-specific cellular immune response measured before vaccination , as assessed by Interferon-gamma (IFN-g) ELISpot using assay-specific cut-off values.

Outcome Time Frame:

up to 8 months

Safety Issue:


Principal Investigator

Elke Jäger, Prof. Dr.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Krankenhaus Nordwest Frankfurt


Germany: Paul-Ehrlich-Institut

Study ID:




Start Date:

August 2011

Completion Date:

Related Keywords:

  • Colorectal Cancer
  • UICC stage IV MSI-H colorectal cancer
  • Colorectal Neoplasms