Vaccination Against MSI Colorectal Cancer

NCT01461148 | Completed Phase 1 DMC

• 1 other identifier: MicOryx
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with advanced microsatellite unstable (MSI-H) colorectal cancer will be vaccinated with three so called frame shift peptides (FSPs), AIM2(-1), HT001(-1) and TAF1B(-1) combined with Montanide® ISA-51 VG. By this, an immune response directed against MSI-induced FSPs that are shared by the majority of MSI-H colorectal cancers can be induced. The aim is to show that vaccination against MSI-induced FSPs is safe and can induce or enhance immune responses against MSI-H colorectal cancer-associated antigens.

Conditions

Colorectal Cancer

Keywords

UICC stage III/IV MSI-H colorectal cancer

Outcome Measures

Primary Outcomes (1)

• immune response against FSP peptides

  A positive immune response is defined as positive delayed-type hypersensitivity (DTH) response against at least one of the peptides or a humoral (ELISA for the detection of FSP-specific IgG/IgM/IgA) and/or CD8 and/or CD4 cellular (IFN gamma ELISpot for the detection of FSP-specific T cells) immune response exceeding the assay specific cut-off values for a positive response against at least one of the three peptides

  every two weeks

Secondary Outcomes (2)

• Tumor response

  every 8 weeks

• safety

  up to 8 months

Study Arms (1)

FSP peptides

EXPERIMENTAL

Vaccination with three FSP peptides

Biological: FSP peptides

Interventions

FSP peptides BIOLOGICAL

100 ug of each FSP (TAF1B(-1), HT001(-1) and AIM2(-1), weekly for 4 consecutive weeks and repeated every four weeks up to a total of 3 cycles.

FSP peptides

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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 disorders.
• 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 permitted.
• Participation in any other clinical trial
• Pregnancy or lactation.
• Women of childbearing potential who are not using a medically acceptable means of contraception.
• Psychiatric or addictive disorders that may compromise the ability to give informed consent.
• Lack of availability of a patient for immunological and clinical follow-up assessment.
• Brain metastases (symptomatic and non-symptomatic)

Sponsors & Collaborators

• Oryx GmbH & Co. KG: lead

Study Sites (1)

Krankenhaus Nordwest

Frankfurt am Main, 60488, Germany

Location

Related Publications (2)

• Kloor M, Reuschenbach M, Pauligk C, Karbach J, Rafiyan MR, Al-Batran SE, Tariverdian M, Jager E, von Knebel Doeberitz M. A Frameshift Peptide Neoantigen-Based Vaccine for Mismatch Repair-Deficient Cancers: A Phase I/IIa Clinical Trial. Clin Cancer Res. 2020 Sep 1;26(17):4503-4510. doi: 10.1158/1078-0432.CCR-19-3517. Epub 2020 Jun 15.

  PMID: 32540851 DERIVED

• Reuschenbach M, Dorre J, Waterboer T, Kopitz J, Schneider M, Hoogerbrugge N, Jager E, Kloor M, von Knebel Doeberitz M. A multiplex method for the detection of serum antibodies against in silico-predicted tumor antigens. Cancer Immunol Immunother. 2014 Dec;63(12):1251-9. doi: 10.1007/s00262-014-1595-y. Epub 2014 Aug 21.

  PMID: 25143232 DERIVED

Related Links

• trial background information

MeSH Terms

Conditions

Colorectal Neoplasms

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

Study Officials

• Elke Jäger, Prof. Dr.

  Krankenhaus Nordwest Frankfurt

  PRINCIPAL INVESTIGATOR

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: October 25, 2011
• First Posted: October 27, 2011
• Study Start: August 1, 2011
• Primary Completion: March 1, 2015
• Study Completion: May 1, 2015
• Last Updated: June 23, 2015

Record last verified: 2015-06

Locations

DE (1)