Scientific 133

Phase I-II Study of HER2 Vaccination with poly(I) • poly(C12U) (Ampligen®) as an Adjuvant in Optimally Treated Breast Cancer Patients
Study Contact
Stephanie Parker | 866.932.8588 | E-Mail

Despite improved tumor response rates and overall survival with current therapies, many breast cancer (BC) patients eventually have disease relapse suggesting the presence of residual microscopic disease. Cancer vaccines given with adjuvants can induce tumor-specific Th1 immunity and result in immunologic eradication of residual tumor cells and potentially prevent disease relapse or tumor spread.  This randomized two-stage study in BC patients will evaluate if Ampligen®, a TLR-3 agonist, given with HER2 vaccination improves vaccine-induced HER2+ immunity.

Study Population / Indication
  1. Patients with stage II, III, or IV breast cancer who have been treated to no evidence of disease or stable bone only disease with definitive therapy will be eligible for study
  2. HER2+ breast cancer: IHC staining (1+, 2+, 3+) or HER2 gene amplification by FISH
  3. Patients cannot be receiving trastuzumab during vaccine therapy
  4. Patients cannot be receiving any concurrent immunomodulators (such as systemic steroids) during vaccine therapy
  5. Patients must have a Zubrod score ≤ 2, be at least 14 days out from last chemotherapy and/or systemic steroids.
  6. Patients cannot be simultaneously enrolled in any other treatment study.
  7. The use of bisphosphanates and/or endocrine therapy will be allowed.
Study Location: University of Washington Medical Center | 1959 NE Pacific Street | Seattle, WA 98195
  1. To choose the most promising (maximum biologic dose (MBD)) of 5 different doses (4, 20, 79, 495, 2000 mcg) of Ampligen administered intradermally as an adjuvant with HER2 vaccination, with respect to toxicity and incidence and magnitude of immune response.
  1. To determine, using MBD of Ampligen (defined in first primary aim), whether Ampligen when given with GM-CSF as a combined adjuvant strategy with HER2 vaccination increases both the incidence and magnitude of HER2 Th1 immunity as compared to the standard GM-CSF adjuvant strategy.
Outcome Measures
Primary endpoints:
  1. Evaluation of immune response among the different treatment arms in Stage I and II:  We will use standard IFN-γ ELISPOT assay to evaluate CD4+ Th1 T cell responses to HER2 immunizing peptides at baseline(prior to 1st vaccine) and at months 4 and 15, post-first-vaccination. A positive immune response will be defined as a post-vaccination T cell precursor frequency >1:50,000 HER2 specific PBMC.  In patients with a baseline precursor frequency >1:50,000, a positive post-vaccination response will be defined as a 2-fold increase in HER2-specific PBMC.

In Stage I, the Ampligen dose group showing both the lowest incidence of toxicity (as described below) and the highest incidence and magnitude of immune response will be chosen as the most immunogenic or MBD. If the 5 Ampligen dose arms result in similar estimates of the outcomes, then the lowest dose will be chosen for Stage II.

  1. Evaluation of safety and systemic toxicity among the different treatment arms in Stage I and II: Safety and systemic toxicity will be determined by chemical and clinical parameters evaluated at baseline, prior to each vaccine, and at month 4. Toxicity grading will be evaluated per CTEP CTCAE 4.0 and monitoring of adverse events (AEs) will be done per FDA and NCI guidelines. The type and grade of toxicities noted during treatment will be summarized. Additionally, stopping rules for accrual to the Ampligen arms will become operational if there is sufficient evidence of excessive toxicity.

Secondary endpoints:

  1. Disease-free and overall survival will be followed and compared among the vaccine treatment arms. Though not statistically powered to this endpoint, large differences if observed between the vaccine treatment groups will be noted and described. Disease-free and overall survival will be defined as time from study enrollment to time of first event.

Related Publications

Concurrent trastuzumab and HER2/neu-specific vaccination in patients with metastatic breast cancer.
Disis ML, Wallace DR, Gooley TA, Dang Y, Slota M, Lu H, Coveler AL, Childs JS, Higgins DM, Fintak PA, dela Rosa C, Tietje K, Link J, Waisman J, Salazar LG.J Clin Oncol. 2009 Oct 1;27(28):4685-92. Epub 2009 Aug 31.


Clinical Description Identifier:  NCT01355393

Clinical Trials Contact

For more information regarding our trials, please call our Patient Coordinator