Description:
This randomized phase I/II trial studies the side effects of vaccine therapy with or without
polysaccharide-K and to see how well it works in treating patients with stage IV human
epidermal growth factor receptor 2 (HER2) positive breast cancer who are receiving
HER2-targeted monoclonal antibody therapy. Vaccines made from HER2 intracellular domain (ICD)
peptide may help the body build an effective immune response to kill tumor cells that express
HER2. Polysaccharide-K may stimulate the immune system in different ways and stop tumor cells
from growing. It is not yet known whether vaccine therapy works better when given with or
without polysaccharide-K in treating breast cancer.
Title
- Brief Title: Vaccine Therapy With or Without Polysaccharide-K in Treating Patients With Stage IV HER2 Positive Breast Cancer Receiving HER2-Targeted Monoclonal Antibody Therapy
- Official Title: Phase I/II Randomized Study of Combination Immunotherapy With or Without Polysaccharide Krestin (PSK®) Concurrently With a HER2 ICD Peptide-Based Vaccine in Patients With Stage IV Breast Cancer Receiving HER2-Targeted Monoclonal Antibody Therapy
Clinical Trial IDs
- ORG STUDY ID:
7866
- SECONDARY ID:
NCI-2013-01377
- SECONDARY ID:
135
- SECONDARY ID:
7866/135
- SECONDARY ID:
7866
- SECONDARY ID:
P30CA015704
- SECONDARY ID:
U19AT006028
- NCT ID:
NCT01922921
Conditions
- HER2/Neu Positive
- Recurrent Breast Carcinoma
- Stage IV Breast Cancer
Interventions
Drug | Synonyms | Arms |
---|
HER-2/neu Intracellular Domain Protein | HER-2 ICD Peptide, HER-2/neu ICD Protein, HER2 ICD, HER2 Intracellular Domain | Arm I (placebo) |
Pertuzumab | 2C4, 2C4 Antibody, MoAb 2C4, Monoclonal Antibody 2C4, Perjeta, rhuMAb2C4, RO4368451 | Arm I (placebo) |
Polysaccharide-K | Glycoproteins, Krestin, KS-2, PSK | Arm II (polysaccharide-K) |
Trastuzumab | ABP 980, Anti-c-ERB-2, Anti-c-erbB2 Monoclonal Antibody, Anti-ERB-2, Anti-erbB-2, Anti-erbB2 Monoclonal Antibody, Anti-HER2/c-erbB2 Monoclonal Antibody, Anti-p185-HER2, c-erb-2 Monoclonal Antibody, HER2 Monoclonal Antibody, Herceptin, Herceptin Biosimilar PF-05280014, Herceptin Trastuzumab Biosimilar PF-05280014, MoAb HER2, Monoclonal Antibody c-erb-2, Monoclonal Antibody HER2, PF-05280014, rhuMAb HER2, RO0452317, Trastuzumab Biosimilar ABP 980, Trastuzumab Biosimilar PF-05280014 | Arm I (placebo) |
Purpose
This randomized phase I/II trial studies the side effects of vaccine therapy with or without
polysaccharide-K and to see how well it works in treating patients with stage IV human
epidermal growth factor receptor 2 (HER2) positive breast cancer who are receiving
HER2-targeted monoclonal antibody therapy. Vaccines made from HER2 intracellular domain (ICD)
peptide may help the body build an effective immune response to kill tumor cells that express
HER2. Polysaccharide-K may stimulate the immune system in different ways and stop tumor cells
from growing. It is not yet known whether vaccine therapy works better when given with or
without polysaccharide-K in treating breast cancer.
Detailed Description
PRIMARY OBJECTIVES:
I. To evaluate the safety of polysaccharide-K (PSK) when given with HER2-directed
immunotherapy.
SECONDARY OBJECTIVES:
I. To evaluate the effect of PSK on natural killer (NK) cell functional activity when given
with HER2-directed immunotherapy.
TERTIARY OBJECTIVES:
I. To investigate the effect of PSK when given with HER2-directed immunotherapy on: serum
levels of pro-inflammatory cytokine and/or chemokines; intermolecular epitope spreading;
serum transforming growth factor (TGF)-beta levels; progression free survival (PFS) and
overall survival (OS).
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive HER2 ICD peptide-based vaccine intradermally (ID) once monthly for 3
months, trastuzumab (or trastuzumab and pertuzumab) per standard of care, and placebo orally
(PO) twice daily (BID) for 4 months.
ARM II: Patients receive HER2 ICD peptide-based vaccine ID and trastuzumab (or trastuzumab
and pertuzumab) as in Arm I and polysaccharide-K PO BID for 4 months.
After completion of study treatment, patients are followed up for 9 months and then twice
annually for 3 years.
Trial Arms
Name | Type | Description | Interventions |
---|
Arm I (placebo) | Active Comparator | Patients receive HER2 ICD peptide-based vaccine ID once monthly for 3 months, trastuzumab (or trastuzumab and pertuzumab) per standard of care, and placebo PO BID for 4 months. | - HER-2/neu Intracellular Domain Protein
- Pertuzumab
- Trastuzumab
|
Arm II (polysaccharide-K) | Experimental | Patients receive HER2 ICD peptide-based vaccine ID and trastuzumab (or trastuzumab and pertuzumab) as in Arm I and polysaccharide-K PO BID for 4 months. | - HER-2/neu Intracellular Domain Protein
- Pertuzumab
- Polysaccharide-K
- Trastuzumab
|
Eligibility Criteria
Inclusion Criteria:
- Patients with stage IV HER2+ breast cancer treated to:
- No evidence of disease (NED), or
- Stable bone only disease after definitive therapy
- HER2 overexpression by immunohistochemistry (IHC) of 2+ or 3+ in the primary tumor or
metastasis; or documented gene amplification by fluorescent in situ hybridization
(FISH) analysis; IHC =< 2+ must have HER2 gene amplification documented by FISH
- Patients must continue HER2-targeted monoclonal antibody therapy dosing per standard
of care through the entire study period (one year)
- HER2-targeted monoclonal antibody therapy is defined as either trastuzumab
monotherapy, or trastuzumab and pertuzumab combination therapy administered per
standard of care
- Patients must be at least 21 days post cytotoxic chemotherapy prior to enrollment
- Patients must be at least 28 days post immunosuppressants prior to enrollment
- Patients must be at least 28 days from use of any mushroom supplements (examples:
turkey tail, reishi, maitake, shiitake) and agree to withhold them for the entire
study period (one year)
- Patients on bisphosphonates and/or endocrine therapy are eligible
- Patients who are having sex that could lead to pregnancy must agree to contraceptive
use during the entire study period
- Patients must have Zubrod performance status score of =< 2
- Patients must have recovered from major infections and/or surgical procedures, and in
the opinion of the investigator, not have significant active concurrent medical
illnesses precluding study treatment
- White blood cell (WBC) >= 3000/mm^3
- Hemoglobin (Hgb) >= 10 g/dl
- Serum creatinine =< 2.0 mg/dl or creatinine clearance > 60 ml/min
- Total bilirubin =< 1.5 mg/dl
- Serum glutamic oxaloacetic transaminase (SGOT) =< 2.5 times the upper limit of normal
- Patients must have adequate cardiac function as demonstrated by normal left
ventricular ejection fraction (LVEF) >= the lower limit of normal for the facility on
multi gated acquisition (MUGA) scan or echocardiogram (ECHO) within 3 months of
enrollment
Exclusion Criteria:
- Patients with any of the following cardiac conditions:
- Restrictive cardiomyopathy
- Unstable angina within 6 months prior to enrollment
- New York Heart Association functional class III-IV heart failure
- Symptomatic pericardial effusion
- Patients with any contraindication to receiving rhu granulocyte macrophage colony
stimulating factor (rhuGM-CSF) based products
- Patients with any clinically significant autoimmune disease requiring active treatment
- Patients receiving any concurrent immunosuppressants
- Patients who are pregnant or breast-feeding
- Patients who are simultaneously enrolled in other treatment studies
- Patients who have received a previous HER2 breast cancer vaccine
- Known hypersensitivity reaction to mushroom products
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Incidence of grade 3 or higher toxicity (including systemic and local injection site reactions) graded per Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events 4.0 |
Time Frame: | Up to 4 months |
Safety Issue: | |
Description: | Evaluated using physical examination and clinical labs. Type and grade of toxicities noted during treatment will be summarized. |
Secondary Outcome Measures
Measure: | Induction of interferon (IFN)-gamma production and cluster of differentiation (CD)107a expression in NK cells, via flow cytometry |
Time Frame: | Up to 16 weeks |
Safety Issue: | |
Description: | Augmentation of NK cell activity is defined by a 2-fold increase in NK cell IFN-gamma production and CD107a expression from baseline after 4 weeks of oral administration of polysaccharide-K. |
Details
Phase: | Phase 1/Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Unknown status |
Lead Sponsor: | University of Washington |
Last Updated
October 2, 2017