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Metastatic Breast CancerPhase 1/2NCT00952692

Study to Assess dHER2+AS15 Cancer Vaccine Given in Combination With Lapatinib to Patients With Metastatic Breast Cancer

A Phase 1/2 study testing dHER2 + AS15 ASCI and Lapatinib in people with Metastatic Breast Cancer, run by Michael Morse, MD at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is a phase I/II study to determine the safety and gain insight into the immune response of the immunologic agent dHER2+AS15 ASCI when administered in combination with lapatinib. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Breast Cancer
What is being tested?
dHER2 + AS15 ASCI and Lapatinib
How many people
12 participants
Where
1 siteUnited States
Study dates
Jul 2009to Apr 2012
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • The following criteria are to be checked at the time of study entry. The patients may only be included in the study if ALL of the following statements are FULLFILLED:
  • The patient (male or female) is at least 18 years old at the time of signature of the informed consent form.
  • Written informed consent has been obtained from the patient prior to the performance of any protocol-specific procedure.
  • The patient is diagnosed with confirmed invasive breast cancer with stage IV disease.
  • Note: If the metastatic disease is restricted to a solitary lesion, its neoplastic nature should be confirmed by cytology or histology.
  • The patient has documented disease progression or relapse following at least one prior standard therapy with trastuzumab (alone or in combination with chemotherapy).
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  • Patients with prior lapatinib use are eligible. Furthermore,
  • The administration of the chemotherapeutic agent(s) should have been stopped for at least 28 days by the time of the first ASCI administration.
  • The administration of trastuzumab alone could be maintained after chemotherapy, but the last dose of trastuzumab should not have been given less than three weeks before the first ASCI administration.
  • The patient will not be given trastuzumab during the trial.
  • For metastatic patients whose disease is ER+ and/or PR+ the following criteria should be met:
  • Patients with visceral disease that requires chemotherapy (eg., patients with liver or lung metastases).
  • Rapidly progressing or life threatening disease, as determined by the investigator.
  • Patients who received hormonal therapy and are no longer benefiting from this therapy.
  • A tumor lesion from the patient biopsied before or during screening shows either:
  • Overexpression of the HER2 protein, as determined by immunohistochemistry (IHC, with result IHC 3+) or
  • Amplification of the HER2 gene as determined by FISH (at least 4 fold i.e. at least 8 copies).
  • Note: Overexpression/amplification measurements must be performed on a metastatic lesion in all cases where such a lesion is sufficiently easily accessible. If however such a biopsy is not possible, then these measurements can be performed on the primary tumor. Use of the primary tumor is to be documented and justified.
  • Ten FFPE tissue sections of the tumor on which the HER2 overexpression/amplification has been done -if available-may be requested. These may be used to retrospectively carry out part of the translational research (i.e. analysis of EGF receptor activity and of the presence of immune effector cells, refer to Section 7).
  • The patient has at least one measurable lesion according to RECIST criteria.
  • The patient has ECOG status of 0 or 1.
  • The patient has adequate bone marrow reserve as indicated by:
  • White blood cell count >/= 3,000/mm3.
  • Neutrophil count >/= 1,500/mm3.
  • Platelet count >/= 100,000/mm3.
  • Hemoglobin levels >/= 10.0 g/dl.
  • The patient has adequate renal function as shown by the creatinine levels (i.e. within the normal range).
  • The patient has adequate hepatic function as shown by serum bilirubin levels i.e:
  • Serum bilirubin levels within the normal limits.
  • Both AST and ALT levels <1.5 times the ULN. Note: However, for patients with liver metastasis, a serum bilirubin level <1.5 times the ULN and both AST and ALT levels <3 times the ULN will be accepted.
  • The patient has a baseline Left Ventricular Ejection Fraction (LVEF) measured by MUGA scan equal to or greater than the LLN for the radiology facility.
  • If the patient is female, she must be of non-childbearing potential, i.e. have a current tubal ligation, hysterectomy, ovariectomy or be post-menopausal, or if she is of childbearing potential, she must practice adequate contraception for 30 days prior to treatment, have a negative pregnancy test and continue such precautions for two months after completion of the study treatment.
  • Adequate contraception is defined as a contraceptive method with failure rate of less than 1% per year when used consistently and correctly (when applicable, as mentioned in the product label) for example abstinence, combined or progestogen oral contraceptives, injectable progestogen, implants of levonorgestrel, oestrogenic vaginal ring, percutaneous contraceptive patches or intrauterine device (IUD) or intrauterine system (IUS), vasectomy with documented azoospermia of the sole male partner or double barrier method (condom or occlusive cap plus spermicidal agent).
  • For azoospermia, "documented" refers to the outcome of the investigator's/ designee's medical examination of the subject or review of the subject's medical history for study eligibility, as obtained via a verbal interview with the subject or from the subject's medical records.
  • Post-menopause: Menopause is the age associated with complete cessation of menstrual cycles, menses, and implies the loss of reproductive potential by ovarian failure. A practical definition accepts menopause after 1 year without menses with an appropriate clinical profile at the appropriate age e.g. > 45 years.
  • Able to swallow and retain oral medication.
  • In the view of the investigator, the patient can and will comply with the requirements of the protocol.

Who cannot join

  • The following criteria should be checked at the time of study entry. If any apply, the patient must not be included in the study:
  • The patient has received > 300 mg/m2 doxorubicin (cumulative dose) or > 600 mg/m2 epirubicin (cumulative dose).
  • The patient is receiving treatment with bisphosphonate UNLESS the biphosphonate treatment was initiated more than three weeks before the first ASCI administration. (See also section 5.3.2.).
  • The patient has received any investigational or non-registered product (drug or vaccine) other than the study treatment(s) within 30 days preceding the first dose of study treatment, or planned use during the study period.
  • The patient is currently receiving amiodarone or has received amiodarone in the 6 months prior to screening.
  • The patient requires concomitant treatment with systemic corticosteroids or any immunosuppressive agents. The use of prednisone, or equivalent, <0.5 mg/kg/day (absolute maximum 40 mg/day), or inhaled corticosteroids or topical steroids is permitted.
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  • The patient has a malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel.
  • Patients with ulcerative colitis.
  • 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 has current active hepatic or biliary's disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment).
  • The patient presents with autoimmune disease (vitiligo and autoimmune thyroid disease is not an exclusion criterion).
  • The patient has a known family history of congenital or hereditary immunodeficiency.
  • The patient has any uncontrolled bleeding disorder or coagulation disorder or thrombocytopenia or pro-thrombotic disorder.
  • The patient has a history of anaphylaxis or severe allergic reaction to vaccines or unknown allergens.
  • The patient has a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to Lapatinib. These include other anilinoquinazolines, such as gefitinib (Iressa), erlotinib (Tarceva), or other chemically related compounds or excipients.
  • The patient is known to be positive for the Human Immunodeficiency Virus (HIV).
  • The patient has (or has had) previous or concomitant malignancies at other sites except effectively treated:
  • Non-melanoma skin cancers or carcinoma in situ of the cervix
  • Malignancy that has been in remission for > 2 years and is considered highly likely to have been cured.
  • The patient has any psychiatric or addictive disorder that may compromise her ability to give informed consent, or to comply with the trial procedures.
  • The patient has any other condition that in the opinion of the investigator might jeopardize the patient's safety or ability to comply with the requirements of the study.
  • The patient is pregnant or lactating.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Duke University Medical Center

    Durham, North Carolina, 27710

Other trials in United States

About this study

Official title: A Monocentric, Open-label Phase I/II Study to Assess dHER2+AS15 Cancer Immunotherapeutic Given in Combination With Lapatinib to Patients With ErbB2 Overexpressing Metastatic Breast Cancer Refractory to Trastuzumab

This is a phase I/II study to determine the safety and gain insight into the immune response of the immunologic agent dHER2+AS15 ASCI when administered in combination with lapatinib. This study is for patients with metastatic breast cancer (invasive breast cancer with stage IV disease) that overexpresses HER2 and is resistant to trastuzumab (Herceptin).

The dHER2 + AS15 candidate Antigen-Specific Cancer Immunotherapeutic (ASCI) contains a recombinant protein termed dHER2, which is a truncated version of the HER2 protein. HER2 is a protein that is commonly overexpressed in breast cancer. This protein is combined with the immunological adjuvant AS15 Adjuvant System from GSK (GlaxoSmithKline), which is a liposomal formulation containing three immunostimulatory components.

Lapatinib is FDA approved for use in combination with capecitabine for the treatment of subjects with advanced or metastatic breast cancer whose tumors overexpress HER2.

Being tested
dHER2 + AS15 ASCI, Lapatinib
Keywords
breast cancer, HER2, Lapatinib, dHER2 ASCI, overexpressing HER2, refractory to trastuzumab
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • dHER2 + AS15 ASCIBiological

    Also called dHER2 ASCI, dHER2 + AS15

    Patients will receive dHER2 ASCI injections IM every 2 weeks for 2 cycles . In between cycles there is 4 weeks without vaccine.

    For each dose of 500µg of dHER2 + AS15 ASCI, two sterile glass vials will be supplied:

    • One vial with the lyophilized preparation containing 500 ug of recombinant dHER2 antigen combined with the immunostimulant.
    • One vial with liquid adjuvant diluent. The final dHER2 + AS15 ASCI for administration is obtained by reconstitution of the lyophilized preparation with the adjuvant diluents. A dHER2 + AS15 ASCI dose consists of 0.5 ml.

  • LapatinibDrug

    Also called Tykerb

    The daily dose of lapatinib is 5 tablets (1250 mg of lapatinib) taken orally at approximately the same time each day for 43 weeks while on study.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The Safety of dHER2+AS15 ASCI When Administered in Combination With Lapatinib Measured by Occurrence of Severe Toxicities (According to CTCAE, Version 3.0)

    Measured: 26 weeks

  2. Number of Participants With T-cell Response

    Positive response is defined as an increase in 40 spots over pre-vaccination frequency

    Measured: 26 weeks

Secondary outcomes (2)

  1. Occurrence of Objective Clinical Response (CR or PR) as Best Overall Response.

    Measured: 26 weeks

  2. Time to Progression

    Defined as the time from first study treatments administration to documented disease progression or death, and censored at the last date of contact for patients whose disease does not progress. Note: In this definition any progression of lesions will count as "progression".

    Measured: 26 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Aug 2009 (estimated)
  2. Study startJul 2009
  3. Primary completionJul 2011
  4. Study completionApr 2012

Resources

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 1/2
Primary purpose
Other
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
12 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00952692
Sponsor's protocol ID
Pro00016847
Other IDs
GSK-dHER2AS15
Status last verified
Nov 2021
First submitted
4 Aug 2009
Last updated
20 Dec 2021
Data monitoring committee
No

Publications

  • Hamilton E, Blackwell K, Hobeika AC, Clay TM, Broadwater G, Ren XR, Chen W, Castro H, Lehmann F, Spector N, Wei J, Osada T, Lyerly HK, Morse MA. Phase 1 clinical trial of HER2-specific immunotherapy with concomitant HER2 kinase inhibition [corrected]. J Transl Med. 2012 Feb 10;10:28. doi: 10.1186/1479-5876-10-28.

    PubMed 22325452

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing dHER2 + AS15 ASCI and Lapatinib in people with Metastatic Breast Cancer, run by Michael Morse, MD at 1 site in United States.

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 37 inclusion and 23 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 20 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 20 Dec 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

The Safety of dHER2+AS15 ASCI When Administered in Combination With Lapatinib Measured by Occurrence of Severe Toxicities (According to CTCAE, Version 3.0) (time frame: 26 weeks). 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 NCT00952692, 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 20 Dec 2021.

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