HER2-Peptide Vaccination of Patients With Solid Tumors (HER2)

A Phase 1 Study of Peptide Vaccination for the Treatment of Patients With Solid Tumors Moderately Expressing HER2/Neu

Investigation of peptide vaccination targeting HER2/neu in patients with metastasized breast or gastric cancer with moderate HER2/neu expression.

Study Overview

• Status: Completed
• Conditions: Breast Cancer; Gastric Cancer
• Intervention / Treatment: Drug: Cyclophosphamide; Drug: Sargramostim; Drug: HER2-Peptid-Vakzine; Drug: Imiquimod

Detailed Description

This is an interventional phase I clinical study to investigate the safety, tolerability and efficacy of HER2-derived peptide vaccination. HLA-A2+ patients with stage IV metastasized breast or gastric cancer with HER2 expression (IHC Score 2+) without gene amplification proved by FISH analysis, with documented stable disease or objective response after at least first line systemic chemotherapy/radiotherapy for advanced disease who have not been treated for the underlying malignant disease for 4 weeks with chemo-, radio- or immunotherapy will be included into the study. The aim of the study is to show safety and tolerability of this immunotherapeutic approach and to investigate efficacy of the immunotherapy.

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Bavaria
    • Munic, Bavaria, Germany, 81675
      • III.Medizinische Klinik und Poliklinik, Klinikum rechts der Isar der TUM

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with stage IV metastasized breast or gastric cancer with documented stable disease or objective response after at least first line chemo/ radiotherapy for advanced disease
• HER2 IHC score 2+ on tumor cells, negative FISH result
• HLA-A2 expression
• Female or male patients aged >= 18 years
• Measurable disease according to RECIST criteria
• ECOG 0-1
• Neutrophile count > 1,5x10^9/l
• WBC > 2,5x10^9/l
• Lymphocyte count > 1x10^9/l
• Hemoglobin > 10g/dl
• Platelets > 100x10^9/l
• Normal renal function (creatinine < 150% ULN)
• Normal liver function (Bilirubin < 150% ULN; ALAT/SGPT and ASAT/SGOT < 300% ULN, except proven metastases)
• Expected survival of at least 6 months
• Concomitant anti-hormonal treatment is allowed
• Female patients within child bearing age must have a negative pregnancy test performed not earlier than 21 days before administration of investigational product. Male and female patients with reproductive potential must agree to employ an effective method of birth control throughout the study and for 6 months discontinuation of investigational product. Postmenopausal women must be amenorrheal for at least 12 months to be considered of non-childbearing potential.
• Men and women of childbearing potential must agree to use a highly effective method of birth control which results in a low failure rate (less than 1% per year) when used consistently and correctly.
• Written informed consent that the patient or a legally authorized representative has been informed about all aspects of the study prior to enrollment and is willing to participate and to be included in the study
• Ability to understand and comply with study and follow-up procedures

Exclusion Criteria:

• Treatment with any other investigational drug within 4 weeks prior to the start of the study medication
• Known hypersensitivity to any components of the study product
• Any severe concomitant disease
• Any disease (including psychotic disorders, drug abuse, active infection, uncontrolled hypertension, unstable angina, heart failure, myocardial infarction within the previous year, serious cardiac arrhythmia requiring medication, hepatic, renal or metabolic disease, obstructive or restrictive lung disease) metabolic dysfunction) and physical examination finding likely (in the investigator's opinion) to affect the evaluation of the study or to put patient at risk associated to treatment with the study medication.
• Any heart disease
• Any serious infection or sepsis
• Any autoimmune disorder
• Infection with HIV, chronic infection with Hepatitis B or C
• Any immunodeficiency syndrome
• Surgery within 4 weeks before study entry
• Prior splenectomy
• Brain metastasis or leptomeningeal involvement
• Systemic application of immunosuppressive drugs including systemic corticosteroids within three weeks before study entry
• Patients eligible or treated with any aproved HER2-targeted therapy as Trastuzumab, Pertzuzumab, T-DM1 or Lapatinib
• Radio-, chemo- or immunotherapy other than study medication in parallel or within 4 weeks prior study start
• Active drug abuse or chronic alcoholism
• Pregnancy or breast feeding
• Female and male patients of reproductive potential unwilling or unable to practice a highly effective method of birth control
• History of non-compliance with medical regimens
• Patients unwilling or unable to comply with the protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HER2-Peptid-Vakzine, Cyclophosphamide; Her2-peptide vaccination, Sargramostim, Imiquimod, Cyclophosphamide	Drug: Cyclophosphamide; Treatment of mild Endoxan application three days before Her2 vaccination; Other Names: Endoxan; Drug: Sargramostim; Sargramostim is part of Her2 vaccination; Other Names: Leukine; Drug: HER2-Peptid-Vakzine; Her2 vaccination is supplemented by Sargramostim and Aldara Creme application; Drug: Imiquimod; Imiquimod is part of Her2 vaccination; Other Names: Aldara 5% Crème

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability of HER2-derived peptide vaccination measured by clinical and chemical parameters.	To examine the safety and tolerability of HER2-derived peptide vaccination in patients with stage IV metastasized breast or gastric cancer with documented stable disease or objective response after at least first line systemic chemotherapy/radiotherapy for advanced disease.	Safety measurement will be assessed up to 113 days relating to start of study treatment

Collaborators and Investigators

• Sponsor: Technical University of Munich
• Investigators: Principal Investigator: Angela Krackhardt, Prof.Dr.med., III.Medizinische Klinik und Poliklinik, Klinikum rechts der Isar der TUM

Study record dates

Study Major Dates

• Study Start: December 1, 2014
• Primary Completion (Actual): July 18, 2017
• Study Completion (Actual): July 13, 2018

Study Registration Dates

• First Submitted: September 25, 2014
• First Submitted That Met QC Criteria: October 23, 2014
• First Posted (Estimate): October 28, 2014

Study Record Updates

• Last Update Posted (Actual): November 20, 2019
• Last Update Submitted That Met QC Criteria: November 18, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Adjuvants, Immunologic; Interferon Inducers; Cyclophosphamide; Imiquimod; Sargramostim
• Other Study ID Numbers: ATZ-1068-KRA-20I