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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00058526




Registration number
NCT00058526
Ethics application status
Date submitted
7/04/2003
Date registered
9/04/2003
Date last updated
15/05/2017

Titles & IDs
Public title
A Dose-escalation Vaccine Trial in HER2-overexpressing Patients With High-risk Breast Cancer
Scientific title
A Multicenter Phase I Open-label Dose-escalation Vaccine Trial of dHER2 Protein With AS15 Adjuvant in HER2-overexpressing Patients With High-risk Breast Cancer
Secondary ID [1] 0 0
104482
Secondary ID [2] 0 0
719125/002
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neoplasms, Breast 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Immunotherapeutic SB719125 (Primary)

Experimental: Cohort 1 - Six doses of dHER2 (20 µg) + AS15 administered at Weeks 0, 2, 4, 6, 10 and 14.

Experimental: Cohort 2 - Six doses of dHER2 (100 µg) + AS15 administered at Weeks 0, 2, 4, 6, 10 and 14.

Experimental: Cohort 3 - 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.

Experimental: Cohort 4 - 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.


Other interventions: Immunotherapeutic SB719125 (Primary)
Intramuscular injection

Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Occurrence of dose limiting toxicity (DLT)
Timepoint [1] 0 0
During the study period (until Week 40 or 43) and the post-study follow-up period (5 years)
Primary outcome [2] 0 0
Occurrence of cardiotoxicity
Timepoint [2] 0 0
During the study period (until Week 40 or 43) and the post-study follow-up period (5 years)
Primary outcome [3] 0 0
Occurrence of Grade 3 or 4 adverse events
Timepoint [3] 0 0
During the study period (until Week 40 or 43) and the post-study follow-up period (5 years)
Primary outcome [4] 0 0
Occurrence of solicited local and general signs and symptoms recorded by the patient on diary cards
Timepoint [4] 0 0
Period of eight days (Day 0 to Day 7) immediately after each administration of the study treatment
Primary outcome [5] 0 0
Occurrence of unsolicited non-serious adverse events
Timepoint [5] 0 0
During the study period (until Week 40 or 43) and the post-study follow-up period (5 years)
Primary outcome [6] 0 0
Occurrence of serious adverse events
Timepoint [6] 0 0
During the study period (until Week 40 or 43) and the post-study follow-up period (5 years)
Primary outcome [7] 0 0
Hematological, biochemical (including auto-immunity) and urinalysis parameters
Timepoint [7] 0 0
During the study period (until Week 40 or 43)
Primary outcome [8] 0 0
Changes in vital signs
Timepoint [8] 0 0
During the entire study period (until Week 40 or 43)
Primary outcome [9] 0 0
Physical examination findings
Timepoint [9] 0 0
During the study period (until Week 40 or 43)
Secondary outcome [1] 0 0
Anti-dHER2, anti-HER2 ECD (extracellular domain), anti-HER2 ICD (intracellular domain) antibody concentrations
Timepoint [1] 0 0
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
Secondary outcome [2] 0 0
Anti-dHER2, anti-HER2 ECD and anti-HER2 ICD seropositivity
Timepoint [2] 0 0
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
Secondary outcome [3] 0 0
In vitro functional activity response (e.g. growth inhibition of HER2-overexpressing breast tumor cells) expressed as a percentage of inhibition
Timepoint [3] 0 0
After four or six administrations of the study treatment
Secondary outcome [4] 0 0
Antibody-dependent cellular cytotoxicity (ADCC, % of lysis) - optionally
Timepoint [4] 0 0
After four or six administrations of the study treatment
Secondary outcome [5] 0 0
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-? and interleukin-5 expressed by concentration (pg/mL)
Timepoint [5] 0 0
At baseline, after Dose 4, after Dose 6, at six months follow-up visit

Eligibility
Key inclusion criteria
Inclusion criteria:

1. Patient must have a previous diagnosis of HER2/neu-positive breast cancer: FISH
positive test (for HercepTest 2+ patients), or, HercepTest 3+ patients.

2. Patients must be Stage II with at least one positive node or Stage III in remission.
Patients must have had standard treatment for their cancer, including lymph node
dissection and at least one course of standard adjuvant treatment.

3. Patient must have completed at least one course of standard adjuvant treatment within
5 years of study entry.

4. Patient may be on concurrent hormonal therapy.

5. Patient must be free of recurrent breast cancer as shown by standard diagnostic tests
at entry onto study.

6. Patient must have a chest X-ray showing no evidence of disease.

7. Patient should have an expected survival of at least 12 months.

8. Written informed consent must be obtained prior to any protocol-specific procedures
being performed.

9. Patient must have Eastern Cooperative Oncology Group (ECOG) Performance Status of 0.

10. Patient must not be pregnant and must use adequate contraception throughout the study
and must plan to not bear children in the future.

11. Patient must not be lactating.

12. Patient must have a negative pregnancy test prior to enrollment. Pregnancy testing
need not be done for patients who are > 55 years of age, post-menopausal or surgically
sterile.

13. Patient must be 40 to 70 years of age inclusive. Patients younger than 40 years of age
may be enrolled if they are sterile and incapable of childbearing.
Chemotherapy-induced amenorrhea is not considered to be a sign of sterility.

14. Patient must have adequate bone marrow reserve as indicated by: WBC =3000/mm3,
neutrophils =1500/ mm3, platelets =100,000 mm3, lymphocytes =1000/mm3, and hemoglobin
=10.0 g/dL.

15. Patient must have an absolute CD4 cell count of >200 cells/mm3.

16. Patient must have adequate renal function.

17. Patient must have adequate hepatic function as indicated by: serum bilirubin within
normal limits, aspartate aminotransferase <1.5 times the upper limit of normal and an
alkaline phosphatase <1.2 times the upper limit of normal. Patients with an alkaline
phosphatase above normal must have negative bone scans and abdominal CT scans prior to
entry onto protocol.

18. Patient must have a baseline left ventricular ejection fraction (LVEF) measured by
multi-gated acquisition (MUGA) scan equal to or greater than the lower limit of normal
for the radiology facility. The serial MUGA scans for each individual must also be
performed at the same radiology facility, using the same equipment in the same manner,
for consistency of method.

19. Patients who had an earlier baseline MUGA scan at the radiological facility of the
investigator's site to be used in the study, such as a MUGA scan done prior to
adjuvant treatment, must meet the above criteria for LVEF AND must also not have had a
decrease in LVEF of above 15 percentage points from the original baseline MUGA scan.
Patients who have not had a MUGA scan done at this radiological facility prior to
adjuvant treatment must have a normal MUGA scan at screening.

20. Patient must not be known to be HIV positive. Results of virology screening must
indicate that the patient has negative serology for HCV (hepatitis C virus) and is
negative for HBsAg (hepatitis B surface antigen). (HBV testing indicating positive
serology (antibodies) is allowed.)
Minimum age
40 Years
Maximum age
70 Years
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

1. Patients who are presently being treated with Herceptin or have been treated with
Herceptin in the past.

2. Patients who have received surgery or chemotherapy treatments within 8 weeks prior to
enrollment. Patients who have received radiation therapy within 12 weeks prior to
enrollment.

3. Patients who have received > 300 mg/m2 doxorubicin (cumulative dose) or > 600 mg/m2
epirubicin (cumulative dose).

4. Patients with any uncontrolled bleeding disorder or coagulation disorder or
thrombocytopenia or prothrombotic disorder.

5. Patients with auto-immune disease such as, but not limited to multiple sclerosis,
lupus, and inflammatory bowel disease, Graves' disease and Hashimoto's disease.

6. Patients with a history of previous anaphylaxis or severe allergic reaction to
vaccines or unknown allergens.

7. Patients with previous splenectomy or radiation to the spleen.

8. Patients who have received a major organ graft (including bone-marrow
transplantation).

9. Patients who require chronic oral treatment (defined as more than 14 days) with
immunosuppressive agents including glucocorticosteroids or other immune-modifying
drugs.

10. Previous or concomitant malignancies at other sites, except effectively treated
non-melanoma skin cancers or carcinoma in situ of the cervix or effectively treated
malignancy that has been in remission for > 2 years and highly likely to have been
cured.

11. Concurrent severe medical problems unrelated to the malignancy, which would
significantly limit full compliance with the study or expose the patient to
unacceptable risk.

12. Patients with previous congestive heart failure or difficult-to-control hypertension.
Patients with known coronary artery disease, arrhythmia requiring treatment,
clinically significant valvular disease, cardiomegaly on chest X-ray, ventricular
hypertrophy on electrocardiogram (EKG) or previous myocardial infarction.

13. Patients with psychiatric or addictive disorders that may compromise the ability to
give informed consent, or comply with the trial procedures.

14. Patients who have received any investigational or non-registered drug or
non-registered vaccine other than the study product within the 30 days preceding the
first dose of study product, or who plan to receive such a drug during the study
period.

15. Patients who have received any immunoglobulins and/or blood products within the 3
weeks prior to study product administration.

16. Patients who have received any commercial vaccine within one week before the first
dose of the study product.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
GSK Investigational Site - East Melbourne
Recruitment hospital [2] 0 0
GSK Investigational Site - Footscray
Recruitment hospital [3] 0 0
GSK Investigational Site - Heidelberg
Recruitment postcode(s) [1] 0 0
3002 - East Melbourne
Recruitment postcode(s) [2] 0 0
3011 - Footscray
Recruitment postcode(s) [3] 0 0
3084 - Heidelberg
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Florida
Country [2] 0 0
United States of America
State/province [2] 0 0
New York
Country [3] 0 0
United States of America
State/province [3] 0 0
North Carolina
Country [4] 0 0
United States of America
State/province [4] 0 0
Washington
Country [5] 0 0
Belgium
State/province [5] 0 0
Bruxelles
Country [6] 0 0
Belgium
State/province [6] 0 0
Charleroi
Country [7] 0 0
Belgium
State/province [7] 0 0
Leuven
Country [8] 0 0
France
State/province [8] 0 0
Lyon Cedex 08
Country [9] 0 0
France
State/province [9] 0 0
Paris Cedex 5
Country [10] 0 0
France
State/province [10] 0 0
Saint-Herblain
Country [11] 0 0
Italy
State/province [11] 0 0
Lazio
Country [12] 0 0
Italy
State/province [12] 0 0
Lombardia
Country [13] 0 0
Italy
State/province [13] 0 0
Umbria

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT00058526
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications