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

NCT01922921 | Completed Phase 1 Results

• 6 other identifiers: 7866NCI-2013-013771357866/135P30CA015704U19AT006028
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

HER2/Neu Positive; Recurrent Breast Carcinoma; Stage IV Breast Cancer

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to 4 months

Secondary Outcomes (1)

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

  Up to 16 weeks

Other Outcomes (5)

• Change in Intermolecular Epitope Spreading Assessed by IFN-gamma Enzyme-linked Immunosorbent Spot Assay

  Baseline to 12 months after completion of treatment

• Change in Pro-inflammatory Serum Cytokine and/or Chemokines Assessed by Luminex Analysis

  Baseline to 24 hours after completion of treatment

• Change in Serum TGF-beta Levels Assessed by Enzyme-linked Immunosorbent Assay

  Baseline to 12 months after completion of treatment

Study Arms (2)

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.

Biological: HER-2/neu Intracellular Domain Protein; Other: Laboratory Biomarker Analysis; Biological: Pertuzumab; Other: Placebo; Biological: 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.

Biological: HER-2/neu Intracellular Domain Protein; Other: Laboratory Biomarker Analysis; Biological: Pertuzumab; Biological: Polysaccharide-K; Biological: Trastuzumab

Interventions

HER-2/neu Intracellular Domain Protein BIOLOGICAL

Given ID

Also known as: HER-2 ICD Peptide, HER-2/neu ICD Protein, HER2 ICD, HER2 Intracellular Domain

Arm I (placebo); Arm II (polysaccharide-K)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm I (placebo); Arm II (polysaccharide-K)

Pertuzumab BIOLOGICAL

Given per standard of care

Also known as: 2C4, 2C4 Antibody, MoAb 2C4, Monoclonal Antibody 2C4, Perjeta, rhuMAb2C4, RO4368451

Arm I (placebo); Arm II (polysaccharide-K)

Placebo OTHER

Given PO

Also known as: placebo therapy, PLCB, sham therapy

Arm I (placebo)

Polysaccharide-K BIOLOGICAL

Given PO

Also known as: Glycoproteins, Krestin, KS-2, PSK

Arm II (polysaccharide-K)

Trastuzumab BIOLOGICAL

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

Arm I (placebo); Arm II (polysaccharide-K)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Washington: lead
• National Cancer Institute (NCI): collaborator
• National Center for Complementary and Integrative Health (NCCIH): collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

pertuzumab; 2C4 antibody; polysaccharide-K; Glycoproteins; Trastuzumab; PF-05280014

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Glycoconjugates; Carbohydrates; Proteins; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Director of Clinical Operations
• Organization: University of Washington

childj@u.washington.edu

2066162305

Study Officials

• Lupe Salazar

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: August 1, 2013
• First Posted: August 14, 2013
• Study Start: February 5, 2014
• Primary Completion: October 31, 2019
• Study Completion: September 1, 2021
• Last Updated: April 18, 2023
• Results First Posted: April 18, 2023

Record last verified: 2023-04

Locations

US (1)