TPIV100 and Sargramostim for the Treatment of HER2 Positive, Stage II-III Breast Cancer in Patients With Residual Disease After Chemotherapy and Surgery

NCT04197687 | Unknown Phase 2 DMC FDA Drug

• 3 other identifiers: MC1835-ACCRU-BR-1701NCI-2019-08038P30CA015083
• Study Type: interventional
• Target: 480
• Locations: 1 country
• Sites: 30

Brief Summary

This phase II trial studies how well TPIV100 and sargramostim work in treating patients with HER2 positive, stage II-III breast cancer that has residual disease after chemotherapy prior to surgery. It also studies why some HER2 positive breast cancer patients respond better to chemotherapy in combination with trastuzumab and pertuzumab. TPIV100 is a type of vaccine made from HER2 peptide that may help the body build an effective immune response to kill tumor cells that express HER2. Sargramostim increases the number of white blood cells in the body following chemotherapy for certain types of cancer and is used to alert the immune system. It is not yet known if TPIV100 and sargramostim will work better in treating patients with HER2 positive, stage II-III breast cancer.

Conditions

Breast Adenocarcinoma; Stage II Breast Cancer AJCC v6 and v7; Stage IIA Breast Cancer AJCC v6 and v7; Stage IIB Breast Cancer AJCC v6 and v7; Stage III Breast Cancer AJCC v7; Stage IIIA Breast Cancer AJCC v7; Stage IIIB Breast Cancer AJCC v7; Stage IIIC Breast Cancer AJCC v7

Outcome Measures

Primary Outcomes (1)

• Invasive disease-free survival (iDFS) between the 2 arms

  iDFS will be defined from the time of randomization to ipsilateral invasive breast tumor recurrence, regional invasive breast cancer recurrence, distant recurrence, death attributable to any cause, including breast cancer, non-breast cancer, or unknown cause, contralateral invasive breast cancer, or second primary non-breast invasive cancer. Will be based on stratified log-rank test at one-sided 0.01 level in an intention-to-treat population, where the stratification is by the randomization stratification factors. The Cox proportional hazards model will be used to adjust for the trial stratification factors (hormone receptor, human leukocyte antigen A classification, status and clinical stage). Subgroup analyses of iDFS will also be performed by stratification factors and other baseline characteristics, with the caveat that statistical power for these subgroup analyses may be limited.

  From time of randomization to recurrence, invasive breast cancer or death, assessed up to 5 years

Secondary Outcomes (5)

• Overall survival

  From randomization to the date of death due to any cause, assessed up to 5 years

• Incidence of adverse events (AEs)

  Up to 24 months

• Immunogenicity assessment

  Up to 5 years

• Complete pathological response

  Baseline

• Vaccine induced HER2-specific T cell responses

  Baseline up to 24 months

Study Arms (3)

Arm I - No pCR (trastuzumab emtansine, TPIV100, sargramostim)

EXPERIMENTAL

Patients receive standard of care maintenance therapy with trastuzumab emtansine and receive TPIV100 ID and sargramostim ID on day 1. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive two additional booster injections of TPIV100 ID and sargramostim ID at 3 and 12 months after completion of trastuzumab emtansine maintenance therapy.

Biological: Multi-epitope HER2 Peptide Vaccine TPIV100; Biological: Sargramostim; Biological: Trastuzumab Emtansine

Arm II - No pCR (trastuzumab emtansine, placebo, sargramostim)

PLACEBO COMPARATOR

Patients receive standard of care maintenance therapy with trastuzumab emtansine and receive placebo ID and sargramostim ID on day 1. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive two additional booster injections of placebo ID and sargramostim ID at 3 and 12 months after completion of trastuzumab emtansine maintenance therapy.

Other: Placebo Administration; Biological: Sargramostim; Biological: Trastuzumab Emtansine

Treatment (pCR)

EXPERIMENTAL

Patients receive standard of care maintenance therapy with trastuzumab and pertuzumab for 1 year in the absence of disease progression or unacceptable toxicity.

Biological: Pertuzumab; Biological: Trastuzumab

Interventions

Multi-epitope HER2 Peptide Vaccine TPIV100 BIOLOGICAL

Given ID

Also known as: HER2/Neu Peptide Vaccine TPIV100, Peptide Vaccine TPIV100, TPIV 100, TPIV-100, TPIV100

Arm I - No pCR (trastuzumab emtansine, TPIV100, sargramostim)

Pertuzumab BIOLOGICAL

permitted at physician's discretion

Also known as: 2C4, 2C4 Antibody, HS627, MoAb 2C4, Monoclonal Antibody 2C4, Omnitarg, Perjeta, Pertuzumab Biosimilar HS627, rhuMAb2C4, RO4368451

Treatment (pCR)

Placebo Administration OTHER

Given ID

Arm II - No pCR (trastuzumab emtansine, placebo, sargramostim)

Sargramostim BIOLOGICAL

Given ID

Also known as: 23-L-Leucinecolony-Stimulating Factor 2, DRG-0012, Leukine, Prokine, rhu GM-CFS, Sagramostim, Sargramostatin

Arm I - No pCR (trastuzumab emtansine, TPIV100, sargramostim); Arm II - No pCR (trastuzumab emtansine, placebo, sargramostim)

Trastuzumab BIOLOGICAL

therapy are at the discretion of the treating physicians

Also known as: ABP 980, ALT02, 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, Herzuma, Kanjinti, MoAb HER2, Monoclonal Antibody c-erb-2, Monoclonal Antibody HER2, Ogivri, Ontruzant, PF-05280014, rhuMAb HER2, RO0452317, SB3, Trastuzumab Biosimilar ABP 980, Trastuzumab Biosimilar ALT02, trastuzumab biosimilar EG12014, Trastuzumab Biosimilar HLX02, Trastuzumab Biosimilar PF-05280014, Trastuzumab Biosimilar SB3, Trastuzumab Biosimilar SIBP-01, Trastuzumab-anns, Trastuzumab-dkst, Trastuzumab-dttb, Trastuzumab-pkrb, Trastuzumab-qyyp, Trazimera

Treatment (pCR)

Trastuzumab Emtansine BIOLOGICAL

at the discretion of the treating physicians.

Also known as: Ado Trastuzumab Emtansine, ADO-Trastuzumab Emtansine, Kadcyla, PRO132365, RO5304020, T-DM1, Trastuzumab-DM1, Trastuzumab-MCC-DM1, Trastuzumab-MCC-DM1 Antibody-Drug Conjugate, Trastuzumab-MCC-DM1 Immunoconjugate

Arm I - No pCR (trastuzumab emtansine, TPIV100, sargramostim); Arm II - No pCR (trastuzumab emtansine, placebo, sargramostim)

Eligibility Criteria

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

You may qualify if:

• PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): Histologically confirmed adenocarcinoma of the breast stage \>= T2 OR \>= N1 based on the 7th edition of tumor, node, metastases (TNM) staging system from the American Joint Committee on Cancer
• PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): Any estrogen receptor (ER) or progesterone receptor (PR) but HER2 positive defined as 3+ staining intensity (on a scale of 0 to 3) by means of immunohistochemistry (IHC) analysis OR gene amplification on fluorescence in situ hybridization (FISH) ratio \>= 2.0
• PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): Willingness to provide adequate pretreatment biopsy sample
• NOTE: Adequate tissue samples defined as core needle biopsy or incisional biopsy or excisional samples that can provide \>= 3 core needle biopsies with at least 14 gauge (G) needle with 12 unstained sections of 5 micron thickness. Fine needle aspiration (FNA) sample alone is not sufficient
• NOTE: Patients without adequate pretreatment biopsy samples must be agreeable to have an additional research biopsy prior to neoadjuvant therapy
• PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, 2
• PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): Willing to employ adequate contraception from the time of pre-registration through 6 months after the final vaccine cycle
• PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): Willing to receive a tetanus vaccination if subject has not had one =\< 1 year prior to pre-registration
• PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): Provide written informed consent
• PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study)
• PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): Willing to provide mandatory tissue and blood samples for correlative research purposes
• PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): Negative pregnancy test done =\< 7 days prior to pre-registration, for persons of childbearing potential only
• NOTE: If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
• REGISTRATION (SAFETY LEAD-IN): Absolute neutrophil count (ANC) \>= 1500/mm\^3 (obtained =\< 28 days prior to registration)
• REGISTRATION (SAFETY LEAD-IN): Platelet count \>= 75,000/mm\^3 (obtained =\< 28 days prior to registration)

You may not qualify if:

• PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:
• Pregnant person
• Nursing person unwilling to stop breast feeding
• Person of child bearing potential who are unwilling to employ adequate contraception from the time of registration through 6 months after the final vaccine cycle
• PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): Clinical evidence of active local recurrence or distant metastases
• NOTE: All patients must have either a positron emission tomography (PET)/computed tomography (CT) or CT chest, abdomen, and pelvis with bone scan to rule out distant metastases =\< 365 days prior to preregistration. If any of these is concerning, follow-up imaging or biopsy should be performed if indicated rule out distant metastases
• PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
• PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): Immunocompromised patients including patients known to be human immunodeficiency virus (HIV) positive or those on chronic steroids
• NOTE: Must be off systemic steroids at least 14 days prior to pre-registration. However, topical steroids, inhalants or steroid eye drops are permitted
• PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): Uncontrolled acute or chronic medical conditions including, but not limited to the following:
• Active infection requiring antibiotics
• Congestive heart failure with New York Heart Association class III or IV; moderate to severe objective evidence of cardiovascular disease
• Myocardial infarction or stroke =\< 6 months prior to pre-registration
• Significant cardiac arrhythmia or unstable angina

Sponsors & Collaborators

• Academic and Community Cancer Research United: lead
• National Cancer Institute (NCI): collaborator

Study Sites (30)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

RECRUITING

Banner University Medical Center - Tucson

Tucson, Arizona, 85719, United States

RECRUITING

University of Arizona Cancer Center-North Campus

Tucson, Arizona, 85719, United States

RECRUITING

Yuma Regional Medical Center

Yuma, Arizona, 85364, United States

WITHDRAWN

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

WITHDRAWN

UC San Diego Moores Cancer Center

La Jolla, California, 92093, United States

NOT YET RECRUITING

Middlesex Hospital

Middletown, Connecticut, 06457, United States

WITHDRAWN

University of Florida Health Science Center - Gainesville

Gainesville, Florida, 32610, United States

RECRUITING

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

RECRUITING

Cleveland Clinic Florida

West Palm Beach, Florida, 33401, United States

WITHDRAWN

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

NOT YET RECRUITING

Illinois CancerCare-Peoria

Peoria, Illinois, 61615, United States

WITHDRAWN

Carle Cancer Center NCI Community Oncology Research Program

Urbana, Illinois, 61801, United States

WITHDRAWN

Siouxland Regional Cancer Center

Sioux City, Iowa, 51101, United States

WITHDRAWN

University Medical Center New Orleans

New Orleans, Louisiana, 70112, United States

RECRUITING

University of Maryland/Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States

NOT YET RECRUITING

Essentia Health NCI Community Oncology Research Program

Duluth, Minnesota, 55805, United States

WITHDRAWN

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

RECRUITING

Coborn Cancer Center at Saint Cloud Hospital

Saint Cloud, Minnesota, 56303, United States

WITHDRAWN

Washington University School of Medicine

St Louis, Missouri, 63110, United States

WITHDRAWN

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

RECRUITING

Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center

Lebanon, New Hampshire, 03756, United States

RECRUITING

FirstHealth of the Carolinas-Moore Regional Hospital

Pinehurst, North Carolina, 28374, United States

RECRUITING

Guthrie Medical Group PC-Robert Packer Hospital

Sayre, Pennsylvania, 18840, United States

WITHDRAWN

Lexington Medical Center

West Columbia, South Carolina, 29169, United States

WITHDRAWN

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, 37232, United States

NOT YET RECRUITING

Inova Fairfax Hospital

Falls Church, Virginia, 22042, United States

WITHDRAWN

Marshfield Medical Center-EC Cancer Center

Eau Claire, Wisconsin, 54701, United States

NOT YET RECRUITING

Saint Vincent Hospital Cancer Center Green Bay

Green Bay, Wisconsin, 54301, United States

WITHDRAWN

Dean Hematology and Oncology Clinic

Madison, Wisconsin, 53717, United States

WITHDRAWN

MeSH Terms

Conditions

Breast Neoplasms

Interventions

pertuzumab; 2C4 antibody; sargramostim; Colony-Stimulating Factors; Trastuzumab; PF-05280014; Ogivri; Ontruzant; trastuzumab biosimilar HLX02; Ado-Trastuzumab Emtansine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Maytansine; Macrolides; Lactones; Organic Chemicals; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Study Officials

• Saranya Chumsri

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 5, 2019
• First Posted: December 13, 2019
• Study Start: February 20, 2020
• Primary Completion: January 15, 2025
• Study Completion: January 15, 2025
• Last Updated: December 18, 2023

Record last verified: 2023-05

Locations

US (30)