Safety and Immunogenicity Study of the New dHER2 Vaccine to Treat HER2-positive Metastatic Breast Cancer

NCT00140738 | Completed Phase 1

• 2 other identifiers: 1006332004-001120-20
• Study Type: interventional
• Target: 3
• Locations: 5 countries
• Sites: 14

Brief Summary

Patients will receive a maximum of 18 injections of dHER2 vaccine in a treatment schedule that will last for up to about a year, and thereafter there will be a follow-up period of about one more year.

Conditions

Neoplasms, Breast

Outcome Measures

Primary Outcomes (2)

• Vaccine-related Grade 3 or 4 toxicity (other than skin toxicity and influenza-like symptoms) according to the Common Terminology Criteria for Adverse Events version 3.0

  During the study.

• Objective clinical response (CR or PR)

  At each tumor evaluation (Visits 7, 14 and 21)

Secondary Outcomes (19)

• Stable disease

  At each tumor evaluation (Visits 7, 14 and 21)

• Mixed response

  At each tumor evaluation (Visits 7, 14 and 21)

• Time to disease progression

  At the time of analysis.

• Time to onset of response, defined as time from first vaccination to the initial response

  At the time of analysis.

• The duration of overall response is measured from the time that measurement criteria are met for complete response or partial response until the first date that recurrent or progressive disease is objectively documented

  At the time of analysis.

Study Arms (2)

Group A

EXPERIMENTAL

Patients receive study vaccinations in 3 consecutive cycles: * In Cycle 1 each patients will receive six vaccinations at two-week intervals followed by evaluation. * In Cycle 2, subjects will patients six vaccinations at two-week intervals followed by evaluation. * In Cycle 3, subjects will patients six vaccinations at three-week intervals.

Biological: GSK Biologicals' 719125

Group B

EXPERIMENTAL

Patients receive study vaccinations as second-line therapy

Biological: GSK Biologicals' 719125

Interventions

GSK Biologicals' 719125 BIOLOGICAL

Patients receive six vaccinations at two-week intervals

Group A; Group B

Eligibility Criteria

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

You may qualify if:

• Female.
• At least 18 years of age.
• Written informed consent to participate in the study.
• Diagnosis of advanced breast cancer. Furthermore, for patients being considered for second-line study treatment only: The patient has received a first-line chemotherapy together with Herceptin - or Herceptin alone - for her metastatic breast disease meeting all of the following conditions:
• i) For patients who have received a first-line chemotherapy together with Herceptin:
• The administration of chemotherapeutic agent(s) has been stopped for at least 3 months, or will have been stopped for at least 3 months by the time of the first study vaccination, and
• The administration of Herceptin alone was maintained after chemotherapy.
• ii) The last dose of Herceptin was given not less than 3 weeks before the study vaccination.
• iii) The patient will not be given Herceptin during the trial.
• A tumor lesion from the patient biopsied before or during screening, shows either i) overexpression of the HER2 protein, as determined by IHC (result: IHC 3+), or ii) amplification of the HER2 gene as determined by FISH (at least 4-fold, i.e., at least 8 copies).
• For patients being considered for first-line study treatment only: The patient's metastatic disease affects the skin and/or the lymph nodes and/or the lungs, but no other organ (with the exception of asymptomatic bone lesions). For patients being considered for second-line study treatment only: The patient's metastatic disease may affect any organ(s) with the exception of the central nervous system (CNS).
• At least one measurable lesion.
• ECOG status of 0 or 1.
• Agree to use effective contraception for the duration of the study and statement not to plan to bear children in the future.
• Result of serum β-HCG pregnancy test at the screening visit is negative. (This does not apply to patients who are not of child-bearing potential)

You may not qualify if:

• For patients being considered for first-line study treatment only:
• Received any chemotherapy for metastatic breast disease.
• Received \>300 mg/m2 doxorubicin (cumulative dose) or \>600 mg/m2 epirubicin (cumulative dose).
• Although hormone therapy as a first-line therapy for metastatic disease is accepted, it must NOT have been started or modified (in nature or dosage) within the 12 weeks before the first study vaccination, and NO such change during the study period may be anticipated.
• Treatment with bisphosphonate UNLESS the bisphosphonate treatment was initiated more than 3 months before first study vaccination.
• Received any investigational or non-registered drug or vaccine other than the study vaccine within the 30 days preceding the first dose of study vaccine, or plans to receive such a drug during the study period.
• Any organ other than skin, lymph nodes, bone and lung is affected by the metastatic disease.
• If the lung is affected: \>3 lung lesions have been detected.
• If the lung is affected: Any lesion measures 30 mm or more (longest diameter).
• If the lung is affected: The lung metastases cause any functional impairment.
• The patient has a history of congestive heart failure or difficult-to-control hypertension, hypercholesterolemia or diabetes.
• The patient has known coronary artery disease, arrhythmia requiring treatment, clinically significant valvular disease, cardiomegaly on chest X-ray, ventricular hypertrophy (found by ECG) or previous myocardial infarction.
• The patient has any acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests.
• The patient presents with autoimmune disease.
• The patient requires chronic administration of immunosuppressive drugs including corticosteroids.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (14)

GSK Investigational Site

Charleroi, 6000, Belgium

Location

GSK Investigational Site

Hasselt, 3500, Belgium

Location

GSK Investigational Site

Ottignies, 1340, Belgium

Location

GSK Investigational Site

Bogotá, 11001000, Colombia

Location

GSK Investigational Site

Lyon, 69373, France

Location

GSK Investigational Site

Montpellier, 34298, France

Location

GSK Investigational Site

Paris, 75248, France

Location

GSK Investigational Site

Saint-Cloud, 92210, France

Location

GSK Investigational Site

Saint-Herblain, 44805, France

Location

GSK Investigational Site

Toulouse, 31052, France

Location

GSK Investigational Site

Vandœuvre-lès-Nancy, 54511, France

Location

GSK Investigational Site

Rome, Lazio, 00133, Italy

Location

GSK Investigational Site

Milan, Lombardy, 20141, Italy

Location

GSK Investigational Site

Lima, Lima 34, Peru

Location

Related Publications (1)

• Curigliano G, Romieu G, Campone M, Dorval T, Duck L, Canon JL, Roemer-Becuwe C, Roselli M, Neciosup S, Burny W, Callegaro A, de Sousa Alves PM, Louahed J, Brichard V, Lehmann FF. A phase I/II trial of the safety and clinical activity of a HER2-protein based immunotherapeutic for treating women with HER2-positive metastatic breast cancer. Breast Cancer Res Treat. 2016 Apr;156(2):301-10. doi: 10.1007/s10549-016-3750-y. Epub 2016 Mar 14.

  PMID: 26975189 BACKGROUND

Related Links

• Results for study 100633 can be found on the GSK Clinical Study Register

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: August 31, 2005
• First Posted: September 1, 2005
• Study Start: March 10, 2005
• Primary Completion: September 29, 2008
• Study Completion: September 29, 2009
• Last Updated: December 27, 2019

Record last verified: 2019-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

BE (3); FR (7); CO (1); PE (1); IT (2)