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

NCT00952692 | Completed Phase 1 Results

• 2 other identifiers: Pro00016847GSK-dHER2AS15
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Metastatic Breast Cancer

Keywords

breast cancer; HER2; Lapatinib; dHER2 ASCI; overexpressing HER2; refractory to trastuzumab

Outcome Measures

Primary Outcomes (2)

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

  26 weeks

• Number of Participants With T-cell Response

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

  26 weeks

Secondary Outcomes (2)

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

  26 weeks

• Time to Progression

  26 weeks

Interventions

dHER2 + AS15 ASCI BIOLOGICAL

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.

Also known as: dHER2 ASCI, dHER2 + AS15

Lapatinib DRUG

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.

Also known as: Tykerb

Eligibility Criteria

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

You may qualify if:

• 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).
• 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:

You may not qualify if:

• 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.
• 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 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.

Sponsors & Collaborators

• Michael Morse, MD: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Related Publications (1)

• 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.

  PMID: 22325452 RESULT

Related Links

• Duke Comprehensive Cancer Center

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Lapatinib

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Michael Morse
• Organization: Duke University

morse004@mc.duke.edu

919-681-3480

Study Officials

• Michael Morse, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: August 4, 2009
• First Posted: August 6, 2009
• Study Start: July 1, 2009
• Primary Completion: July 1, 2011
• Study Completion: April 1, 2012
• Last Updated: December 20, 2021
• Results First Posted: December 20, 2021

Record last verified: 2021-11

Locations

US (1)