Neoplasms, BreastPhase 1NCT00140738
Safety and Immunogenicity Study of the New dHER2 Vaccine to Treat HER2-positive Metastatic Breast Cancer
A Phase 1 study testing GSK Biologicals' 719125 in people with Neoplasms, Breast, run by GlaxoSmithKline at 14 sites in 5 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Neoplasms, Breast
- What is being tested?
- GSK Biologicals' 719125
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 14 sitesin 5 countries
- Study dates
- 10 Mar 2005to 29 Sep 2009
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
- 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
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- The administration of Herceptin alone was maintained after chemotherapy.
- The last dose of Herceptin was given not less than 3 weeks before the study vaccination.
- 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)
- Adequate bone marrow reserve.
- Adequate renal function.
- Adequate hepatic function.
- Baseline LVEF measured by MUGA scan equal to or greater than the lower limit of normal for the radiology facility.
- Results of a viral screening tests (HCV, and HBV surface antigen) on samples taken at the screening visit are both negative.
- Investigator believes that the patient can and will comply with the requirements of the protocol.
- The following condition applies to centers in France only: A subject will be eligible for inclusion in this study if he/she is either affiliated to or a beneficiary of a social security category. It is the investigator's responsibility to ensure and to document (in source document - patient notes) that the patient is either affiliated to or a beneficiary of a social security category.
Who cannot join
- 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.
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- For patients being considered for first-line study treatment, any of the following will result in exclusion of the patient:
- 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 sponsor may during the study instruct sites that no further patients with lung metastases are to be included. Receipt of such instructions from the sponsor constitutes an exclusion criterion for all further patients with lung metastases.For patients being considered for second-line study treatment, the presence of lung metastases that cause any functional impairment following will result in exclusion of the patient.
- 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.
- Medical history includes splenectomy or irradiation to the spleen.
- Known family history of congenital or hereditary immunodeficiency.
- Received major organ graft (including bone-marrow transplantation).
- Any uncontrolled bleeding disorder or coagulation disorder or thrombocytopenia or prothrombotic disorder.
- History of anaphylaxis or severe allergic reaction to vaccines or unknown allergens.
- HIV positive.
- Previous or concomitant malignancies at other sites, except (i) effectively treated non-melanoma skin cancers or carcinoma in situ of the cervix, and (ii) effectively treated malignancy that has been in remission for >2 years and which is considered highly likely to have been cured.
- Pregnant or lactating.
- Any psychiatric or addictive disorder that may compromise ability to give informed consent, or to comply with the trial procedures.
- Any history of alcohol or drug abuse.
- Any other condition is present that in the opinion of the investigator might jeopardize the patient's safety or ability to comply with requirements of the study
- Received any commercial vaccine within one week before the first study vaccination.
Trial locations and contacts
14 sites in 5 countries.
14 sites in 5 countries
France7 sites
GSK Investigational Site
Lyon, 69373
GSK Investigational Site
Montpellier, 34298
GSK Investigational Site
Paris, 75248
GSK Investigational Site
Saint-Cloud, 92210
GSK Investigational Site
Saint-Herblain, 44805
GSK Investigational Site
Toulouse, 31052
GSK Investigational Site
Vandœuvre-lès-Nancy, 54511
Belgium3 sites
GSK Investigational Site
Charleroi, 6000
GSK Investigational Site
Hasselt, 3500
GSK Investigational Site
Ottignies, 1340
Italy2 sites
GSK Investigational Site
Milan, Lombardy, 20141
GSK Investigational Site
Rome, Lazio, 00133
About this study
Official title: A Multicenter, Open-label Phase I/II Trial of the Safety and Efficacy of the dHER2 Recombinant Protein Combined With Immunological Adjuvant AS15 in Patients With Metastatic Breast Cancer Overexpressing HER2/Neu
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.
Read the detailed description
This Phase I/II study will be conducted according to a multicenter, open-label design. At least 20 patients will receive the vaccine as first-line and at least 20 as second-line treatment. The treatment will comprise a maximum of 18 injections of dHER2 vaccine. Follow-up phase: This will commence with the end-of-treatment examination, followed by examinations three months, six months and twelve months after the last study vaccination. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.
- Conditions
- Neoplasms, Breast
- Being tested
- GSK Biologicals' 719125
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK Biologicals' 719125Biological
Patients receive six vaccinations at two-week intervals
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Biological: GSK Biologicals' 719125 |
| Group B | Experimental | Patients receive study vaccinations as second-line therapy Receives: Biological: GSK Biologicals' 719125 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: During the study.
Objective clinical response (CR or PR)
Measured: At each tumor evaluation (Visits 7, 14 and 21)
Secondary outcomes (19)
Stable disease
Measured: At each tumor evaluation (Visits 7, 14 and 21)
Mixed response
Measured: At each tumor evaluation (Visits 7, 14 and 21)
Time to disease progression
Measured: At the time of analysis.
Time to onset of response, defined as time from first vaccination to the initial response
Measured: 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
Measured: At the time of analysis.
Anti-dHER2, anti-HER2 ECD and anti-HER2 ICD seropositivity.
Measured: At all point during treatment (as specified in the study schedule)
Functional activity in vitro
Measured: At all point during treatment (as specified in the study schedule)
Frequency of cellular immune response in vitro to dHER2, HER2 ECD and HER2 ICD
Measured: At all point during treatment (as specified in the study schedule)
Adverse events of Grades 3 and 4
Measured: Throughout the study
Adverse events related to potential cardiotoxicity
Measured: Throughout the study
Solicited local and general signs and symptoms (recorded by the patients on diary cards)
Measured: During a period of four days following each administration of study vaccine
Unsolicited adverse events (serious and non-serious)
Measured: At any time during the study
Unsolicited serious adverse events
Measured: At any time during the study
Any documented toxicity
Measured: At any time during the study
Left ventricular ejection fraction
Measured: At screening and at appropriate intervals during treatment.
Laboratory values: hematological and biochemical variables (including coagulation).
Measured: at all point during treatment as specified in the study schedule
Vital signs.
Measured: at each administration
Electrocardiographic results
Measured: at the end of cycle 1 and cycle 2 and at first follow-up visit
Results of physical examination
Measured: At each visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Sep 2005 (estimated)
- Study start10 Mar 2005
- Primary completion29 Sep 2008
- Study completion29 Sep 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Neoplasms, BreastStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00140738
- Sponsor's protocol ID
- 100633
- Other IDs
- 2004-001120-20, 2004
- Status last verified
- Dec 2019
- First submitted
- 31 Aug 2005
- Last updated
- 27 Dec 2019
- Results posted
- No
- Individual data sharing
- Yes: IPD is available via the Clinical Study Data Request site (click on the link provided below)
Publications
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.
PubMed 26975189
Study at a glance
From the registry record, last updated by the sponsor on 27 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Open-label Phase I/II Trial of the Safety and Efficacy of the dHER2 Recombinant Protein Combined With Immunological Adjuvant AS15 in Patients With Metastatic Breast Cancer Overexpressing HER2/Neu
- ClinicalTrials.gov ID
- NCT00140738
- Acronym / sponsor ID
- 100633
- Conditions
- Neoplasms, Breast
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 3 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 10 Mar 2005 (actual)
- Primary completion
- 29 Sep 2008 (actual)
- Study completion
- 29 Sep 2009 (actual)
- First posted
- 1 Sep 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This Phase I/II study will be conducted according to a multicenter, open-label design. At least 20 patients will receive the vaccine as first-line and at least 20 as second-line treatment. The treatment will comprise a maximum of 18 injections of dHER2 vaccine. Follow-up phase: This will commence with the end-of-treatment examination, followed by examinations three months, six months and twelve months after the last study vaccination. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group A | Experimental | Biological: GSK Biologicals' 719125Patients 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. |
| Group B | Experimental | Biological: GSK Biologicals' 719125Patients receive study vaccinations as second-line therapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- 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:
- 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
Key exclusion criteria (29 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GSK Biologicals' 719125Patients receive six vaccinations at two-week intervals | Biological | Group A, Group B |
Primary outcome
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
Time frame: During the study.
Objective clinical response (CR or PR)
Time frame: At each tumor evaluation (Visits 7, 14 and 21)
19 secondary outcomes
Stable disease
Time frame: At each tumor evaluation (Visits 7, 14 and 21)
Mixed response
Time frame: At each tumor evaluation (Visits 7, 14 and 21)
Time to disease progression
Time frame: At the time of analysis.
Time to onset of response, defined as time from first vaccination to the initial response
Time frame: 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
Time frame: At the time of analysis.
Anti-dHER2, anti-HER2 ECD and anti-HER2 ICD seropositivity.
Time frame: At all point during treatment (as specified in the study schedule)
Functional activity in vitro
Time frame: At all point during treatment (as specified in the study schedule)
Frequency of cellular immune response in vitro to dHER2, HER2 ECD and HER2 ICD
Time frame: At all point during treatment (as specified in the study schedule)
Adverse events of Grades 3 and 4
Time frame: Throughout the study
Adverse events related to potential cardiotoxicity
Time frame: Throughout the study
Solicited local and general signs and symptoms (recorded by the patients on diary cards)
Time frame: During a period of four days following each administration of study vaccine
Unsolicited adverse events (serious and non-serious)
Time frame: At any time during the study
Unsolicited serious adverse events
Time frame: At any time during the study
Any documented toxicity
Time frame: At any time during the study
Left ventricular ejection fraction
Time frame: At screening and at appropriate intervals during treatment.
Laboratory values: hematological and biochemical variables (including coagulation).
Time frame: at all point during treatment as specified in the study schedule
Vital signs.
Time frame: at each administration
Electrocardiographic results
Time frame: at the end of cycle 1 and cycle 2 and at first follow-up visit
Results of physical examination
Time frame: At each visit
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Dec 2019.
- Background: PubMed 26975189Curigliano 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.
- Results for study 100633 can be found on the GSK Clinical Study RegisterLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. IPD is available via the Clinical Study Data Request site (click on the link provided below)
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
14 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing GSK Biologicals' 719125 in people with Neoplasms, Breast, run by GlaxoSmithKline at 14 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in France, Belgium, Italy, Colombia, Peru. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 (time frame: During the study.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00140738, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Dec 2019.