CompletedNCT01922921Updated Apr 18, 2023Results posted

Vaccine Therapy With or Without Polysaccharide-K in Patients With Stage IV HER2 Positive Breast Cancer Receiving HER2-Targeted Monoclonal Antibody Therapy

A Phase 1/2 interventional study of HER-2/neu Intracellular Domain Protein and Laboratory Biomarker Analysis in HER2/Neu Positive, Recurrent Breast Carcinoma and Stage IV Breast Cancer, sponsored by University of Washington. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-04-18.

Sponsored by University of Washington · Phase 1/2, Interventional, and Treatment

Phase: Phase 1/2
Study type: Interventional
Enrollment: 31
Allocation: Randomized
Ages: 18 Years and older
Sex: All

Study summary

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.

Read the 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.

Conditions studied

HER2/Neu Positive
Recurrent Breast Carcinoma
Stage IV Breast Cancer

Browse trials for

Breast Neoplasms 12,544

In context

Breast Neoplasms

12,544 studies on the registry are indexed under Breast Neoplasms; 2,892 are open to participants now.

This study's enrollment of 31 is below the median of 72 across 9,303 interventional studies indexed under Breast Neoplasms.

Browse Breast Neoplasms studies →

Lead sponsor

University of Washington is the lead sponsor of 1,397 studies on the registry; 225 are open to participants now.

Of its 154 completed or terminated interventional studies of FDA-regulated products, 132 (86%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

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

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

Study design

Phase: Phase 1 / Phase 2
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Double (Participant, Investigator)
Enrollment: 31 participants (actual)

Study arms

Active comparator
Arm I (placebo)
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.
Biological: HER-2/neu Intracellular Domain Protein · Other: Laboratory Biomarker Analysis · Biological: Pertuzumab · Other: Placebo · Biological: Trastuzumab
Experimental
Arm II (polysaccharide-K)
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.
Biological: HER-2/neu Intracellular Domain Protein · Other: Laboratory Biomarker Analysis · Biological: Pertuzumab · Biological: Polysaccharide-K · Biological: Trastuzumab

Interventions

BiologicalHER-2/neu Intracellular Domain Protein
Given ID
Also known as: HER-2 ICD Peptide, HER-2/neu ICD Protein, HER2 ICD, HER2 Intracellular Domain
OtherLaboratory Biomarker Analysis
Correlative studies
BiologicalPertuzumab
Given per standard of care
Also known as: 2C4, 2C4 Antibody, MoAb 2C4, Monoclonal Antibody 2C4, Perjeta, rhuMAb2C4, RO4368451
OtherPlacebo
Given PO
Also known as: placebo therapy, PLCB, sham therapy
BiologicalPolysaccharide-K
Given PO
Also known as: Glycoproteins, Krestin, KS-2, PSK
BiologicalTrastuzumab
Given per standard of care
Also known as: 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

What researchers measure

Primary outcomes

Number of Patients With Grade 3 or Higher Toxicity Per Study Arm.
Evaluated using physical examinations and clinical labs by type and grade of toxicities noted during treatment, There were graded per Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events 4.0.
Time frame: Up to 4 months

Secondary outcomes

Induction of Interferon (IFN)-Gamma Production and Cluster of Differentiation (CD)107a Expression in NK Cells, Via Flow Cytometry
Augmentation of NK cell activity is defined by a 2-fold increase (at time of maximal change) in NK cell IFN-gamma production and CD107a expression For the results we used CD56 which is the accepted phenotypic marker for natural killer (NK) cells and CD16 which is a receptor on NK cells that facilitates antibody-dependent cellular cytotoxicity (ADCC). CD56dim are typically responsible for cytolytic activity and targets cell killing, whereas, CD56bright are the main source of cytokine production (i.e. IFN-gamma). CD56dim CD16bright NK cells represent at least 90% of all peripheral blood NK cells with a maximum of 10% as CD56bright NK cells We compared the baseline expression of CD56brightCD16dim or CD56dimCD16bright (prior to start of study treatment) to the maximum expression of CD56brightCD16dim or CD56dimCD16bright at 1 of 4 timepoints after the start of the oral administration of study treatment (polysaccharide-K/placebo (either week 4, 8, 12 or 16).
Time frame: Up to 16 weeks

Other outcomes

Change in Intermolecular Epitope Spreading Assessed by IFN-gamma Enzyme-linked Immunosorbent Spot Assay
IFN-γ ELISPOT assay will be used to evaluate T cell precursor frequency to specific breast tumor antigens. A positive immune response will be defined as a post-vaccination T cell precursor frequency \>1:20,000 antigen-specific PBMCs. In patients with a baseline precursor frequency \>1:20,000, a positive post-vaccination immune response will be defined as a 2-fold increase in antigen-specific PBMC. PBMC will be cryopreserved and subsequently be thawed at time of analysis.
Time frame: Baseline to 12 months after completion of treatment
Change in Pro-inflammatory Serum Cytokine and/or Chemokines Assessed by Luminex Analysis
Time frame: Baseline to 24 hours after completion of treatment
Change in Serum TGF-beta Levels Assessed by Enzyme-linked Immunosorbent Assay
Time frame: Baseline to 12 months after completion of treatment
OS
Time frame: Up to 3 years
PFS
Time frame: Up to 3 years

Results

Posted Apr 18, 2023

Participant flow

Participant flow — Overall Study
Milestone	Arm I (Placebo)	Arm II (Polysaccharide-K)
Started	16	15
Completed	15	14
Not completed	1	1

Outcome measures

PrimaryNumber of Patients With Grade 3 or Higher Toxicity Per Study Arm.

Evaluated using physical examinations and clinical labs by type and grade of toxicities noted during treatment, There were graded per Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events 4.0.

Time frame:: Up to 4 months
Reported as:: Count of participants · Participants

Number of Patients With Grade 3 or Higher Toxicity Per Study Arm.
Participants	Arm I (Placebo)	Arm II (Polysaccharide-K)
Number of Patients With Grade 3 or Higher Toxicity Per Study Arm.	2	0

SecondaryInduction of Interferon (IFN)-Gamma Production and Cluster of Differentiation (CD)107a Expression in NK Cells, Via Flow Cytometry

Augmentation of NK cell activity is defined by a 2-fold increase (at time of maximal change) in NK cell IFN-gamma production and CD107a expression For the results we used CD56 which is the accepted phenotypic marker for natural killer (NK) cells and CD16 which is a receptor on NK cells that facilitates antibody-dependent cellular cytotoxicity (ADCC). CD56dim are typically responsible for cytolytic activity and targets cell killing, whereas, CD56bright are the main source of cytokine production (i.e. IFN-gamma). CD56dim CD16bright NK cells represent at least 90% of all peripheral blood NK cells with a maximum of 10% as CD56bright NK cells We compared the baseline expression of CD56brightCD16dim or CD56dimCD16bright (prior to start of study treatment) to the maximum expression of CD56brightCD16dim or CD56dimCD16bright at 1 of 4 timepoints after the start of the oral administration of study treatment (polysaccharide-K/placebo (either week 4, 8, 12 or 16).

Time frame:: Up to 16 weeks
Reported as:: Count of participants · Participants

Induction of Interferon (IFN)-Gamma Production and Cluster of Differentiation (CD)107a Expression in NK Cells, Via Flow Cytometry
Participants	Arm I (Placebo) - CD56dim CD16bright	Arm II (Polysaccharide-K) - CD56dim CD16bright	Arm I (Placebo) - CD56bright CD16dim	Arm II (Polysaccharide-K) - CD56bright CD16dim
INF gamma+ — >=2 fold increase	4	9	4	7
INF gamma+ — <2 fold increase	5	4	5	6
CD107+ — >=2 fold increase	3	8	3	6
CD107+ — <2 fold increase	6	5	6	7

Other pre-specifiedChange in Intermolecular Epitope Spreading Assessed by IFN-gamma Enzyme-linked Immunosorbent Spot Assay

IFN-γ ELISPOT assay will be used to evaluate T cell precursor frequency to specific breast tumor antigens. A positive immune response will be defined as a post-vaccination T cell precursor frequency \>1:20,000 antigen-specific PBMCs. In patients with a baseline precursor frequency \>1:20,000, a positive post-vaccination immune response will be defined as a 2-fold increase in antigen-specific PBMC. PBMC will be cryopreserved and subsequently be thawed at time of analysis.

Time frame:: Baseline to 12 months after completion of treatment