A Dose-escalation Vaccine Trial in HER2-overexpressing Patients With High-risk Breast Cancer

Phase 1

Completed

• Conditions: Neoplasms, Breast
• Interventions: Biological: Immunotherapeutic SB719125 (Primary)

• Registration Number: NCT00058526
• Lead Sponsor: GlaxoSmithKline

Brief Summary

Treatment phase:

The purpose of this study is to evaluate the safety and the immune response elicited by a new anti-cancer therapy in patients with breast cancer in remission but who are at high risk of relapse. The study product is an immunotherapeutic consisting of the recombinant dHER2 protein combined with an immunostimulant called AS15. The study aims to determine the optimal of three different dose levels of dHER2 combined with the same fixed dose of AS15 by assessing the safety and the immune response elicited after a series of injections of the study product.

Five-year follow-up phase:

This part of the study aims to assess any late onset toxicity of the study treatment through yearly follow-up visits and to monitor the patients' survival and disease status up to five years after the last administration of the study treatment. The patients' immune response is also measured to assess the robustness of the immune response elicited by the study treatment.

Detailed Description

Not available

Study Timeline

• Study Start: 2003-03-20
• Study First Submitted: 2003-04-07
• Study First Submitted QC: 2003-04-08
• Study First Posted: 2003-04-09
• Primary Completion: 2006-09-06
• Study Completion: 2006-09-06
• Status Verified: 2017-05
• Last Update Submitted: 2017-05-12
• Last Update Posted: 2017-05-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 61

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 4	Immunotherapeutic SB719125 (Primary)	Three doses of dHER2 (20 µg) + AS15 administered at Weeks 0, 4, and 14. Patients in this cohort can receive two booster doses at Weeks 34 and 38, respectively.
Cohort 2	Immunotherapeutic SB719125 (Primary)	Six doses of dHER2 (100 µg) + AS15 administered at Weeks 0, 2, 4, 6, 10 and 14.
Cohort 1	Immunotherapeutic SB719125 (Primary)	Six doses of dHER2 (20 µg) + AS15 administered at Weeks 0, 2, 4, 6, 10 and 14.
Cohort 3	Immunotherapeutic SB719125 (Primary)	Six doses of dHER2 (500 µg) + AS15 administered at Weeks 0, 2, 4, 6, 10 and 14. Patients in this cohort can receive two booster doses at Weeks 34 and 38, respectively.

Primary Outcome Measures

Name	Time	Method
Occurrence of solicited local and general signs and symptoms recorded by the patient on diary cards	Period of eight days (Day 0 to Day 7) immediately after each administration of the study treatment
Occurrence of cardiotoxicity	During the study period (until Week 40 or 43) and the post-study follow-up period (5 years)
Occurrence of serious adverse events	During the study period (until Week 40 or 43) and the post-study follow-up period (5 years)
Occurrence of dose limiting toxicity (DLT)	During the study period (until Week 40 or 43) and the post-study follow-up period (5 years)
Occurrence of unsolicited non-serious adverse events	During the study period (until Week 40 or 43) and the post-study follow-up period (5 years)
Hematological, biochemical (including auto-immunity) and urinalysis parameters	During the study period (until Week 40 or 43)
Occurrence of Grade 3 or 4 adverse events	During the study period (until Week 40 or 43) and the post-study follow-up period (5 years)
Changes in vital signs	During the entire study period (until Week 40 or 43)
Physical examination findings	During the study period (until Week 40 or 43)

Secondary Outcome Measures

Name	Time	Method
Anti-dHER2, anti-HER2 ECD and anti-HER2 ICD seropositivity	Two weeks after the fourth and sixth study treatment administrations (Week 6 and Week 14) and at the three and six months follow-up visit (Week 26 and Week 40). At yearly visits during the five-year follow-up period
Anti-dHER2, anti-HER2 ECD (extracellular domain), anti-HER2 ICD (intracellular domain) antibody concentrations	Two weeks after the fourth and sixth study treatment administrations (Week 6 and Week 14) and at the three and six months follow-up visit (Week 26 and Week 40). At yearly visits during the five-year follow-up period
In vitro functional activity response (e.g. growth inhibition of HER2-overexpressing breast tumor cells) expressed as a percentage of inhibition	After four or six administrations of the study treatment
Antibody-dependent cellular cytotoxicity (ADCC, % of lysis) - optionally	After four or six administrations of the study treatment
In vitro cellular immune response to dHER2, HER2 ECD and HER2 ICD as shown by lymphoproliferative response (expressed by stimulation index) and by secretion of interferon-γ and interleukin-5 expressed by concentration (pg/mL)	At baseline, after Dose 4, after Dose 6, at six months follow-up visit

Trial Locations

Locations (1)

GSK Investigational Site; 🇮🇹 Perugia, Umbria, Italy