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
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Metastatic Breast Cancer
- Sponsor
- Michael Morse, MD
- Enrollment
- 12
- Locations
- 1
- Primary Endpoint
- The Safety of dHER2+AS15 ASCI When Administered in Combination With Lapatinib Measured by Occurrence of Severe Toxicities (According to CTCAE, Version 3.0)
- Status
- Completed
- Last Updated
- 4 years ago
Overview
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.
Investigators
Michael Morse, MD
Associate Professor
Duke University
Eligibility Criteria
Inclusion Criteria
- •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.
Exclusion Criteria
- •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.
Outcomes
Primary Outcomes
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
Number of Participants With T-cell Response
Time Frame: 26 weeks
Positive response is defined as an increase in 40 spots over pre-vaccination frequency
Secondary Outcomes
- Time to Progression(26 weeks)
- Occurrence of Objective Clinical Response (CR or PR) as Best Overall Response.(26 weeks)