AzTrials
AzTrials

Breast AdenocarcinomaPhase 2NCT04197687

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

A Phase 2 study testing Multi-epitope HER2 Peptide Vaccine TPIV100, Pertuzumab and Sargramostim in people with Breast Adenocarcinoma and Stage II Breast Cancer AJCC v6 and v7, run by Academic and Community Cancer Research United at 30 sites in United States.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record

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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Multi-epitope HER2 Peptide Vaccine TPIV100, Pertuzumab and Sargramostim
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
480 participants
Where
30 sitesUnited States
Study dates
20 Feb 2020to 15 Jan 2025
Phase
Phase 2

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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)
  • REGISTRATION (SAFETY LEAD-IN): Hemoglobin >= 9.0 g/dL (obtained =< 28 days prior to registration)
  • REGISTRATION (SAFETY LEAD-IN): Direct bilirubin < 1.5 x upper limit of normal (ULN) (obtained =< 28 days prior to registration)
  • REGISTRATION (SAFETY LEAD-IN): Aspartate transaminase (AST) =< 3 x ULN (obtained =< 28 days prior to registration)
  • REGISTRATION (SAFETY LEAD-IN): Creatinine =< 2 x ULN (obtained =< 28 days prior to registration)
  • REGISTRATION (SAFETY LEAD-IN): Prothrombin time (PT)/international normalized ratio (INR)/ partial thromboplastin time (PTT) =< 1.5 x ULN OR if patient is receiving anticoagulant therapy and PT or PTT is within therapeutic range of intended use of coagulant (obtained =< 28 days prior to registration)
  • REGISTRATION (SAFETY LEAD-IN): Completed planned curative breast surgeries (not including any future breast reconstructive surgery) and any radiation therapy >= 30 days prior to registration
  • REGISTRATION (SAFETY LEAD-IN): Completed last cycle of chemotherapy >= 90 days prior to registration
  • NOTE: Prior to registration, patients must not receive > 8 cycles of TDM-1 maintenance therapy after surgery
  • REGISTRATION (SAFETY LEAD-IN): Any residual disease after trastuzumab +/- pertuzumab based neoadjuvant chemotherapy warranted T-DM1 as per treating physician
  • REGISTRATION (SAFETY LEAD-IN): Adequate tissue specimens from both pre-treatment biopsy and surgery must be submitted. Adequate tissue samples defined as core needle biopsy or incisional biopsy or excisional samples that can provide >= 3 core needle biopsies with at least 14G needle with 12 unstained sections of 5 micron thickness
  • NOTE: Fine needle aspiration (FNA) sample alone is not sufficient
  • REGISTRATION (SAFETY LEAD-IN): Negative pregnancy test done =< 7 days prior to 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): ECOG performance status (PS) 0, 1, 2
  • REGISTRATION (SAFETY LEAD-IN): Willing to employ adequate contraception from the time of registration through 6 months after the final vaccine cycle
  • REGISTRATION - FOR PATIENTS WITH NO RESIDUAL DISEASE (pCR) - (PHASE II): ECOG performance status (PS) 0, 1, 2
  • REGISTRATION - FOR PATIENTS WITH NO RESIDUAL DISEASE (pCR) - (PHASE II): Absolute neutrophil count (ANC) >= 1500/mm^3 (obtained =< 28 days prior to registration)
  • REGISTRATION - FOR PATIENTS WITH NO RESIDUAL DISEASE (pCR) - (PHASE II): Platelet count >= 75,000/mm^3 (obtained =< 28 days prior to registration)
  • REGISTRATION - FOR PATIENTS WITH NO RESIDUAL DISEASE (pCR) - (PHASE II): Hemoglobin >= 9.0 g/dL (obtained =< 28 days prior to registration)
  • REGISTRATION - FOR PATIENTS WITH NO RESIDUAL DISEASE (pCR) - (PHASE II): Direct bilirubin < 1.5 x upper limit of normal (ULN) (obtained =< 28 days prior to registration)
  • REGISTRATION - FOR PATIENTS WITH NO RESIDUAL DISEASE (pCR) - (PHASE II): Aspartate transaminase (AST) =< 3 x ULN (obtained =< 28 days prior to registration)
  • REGISTRATION - FOR PATIENTS WITH NO RESIDUAL DISEASE (pCR) - (PHASE II): Calculated serum creatinine clearance of >= 50 mL/minute (min.) (obtained =< 28 days prior to registration)
  • REGISTRATION - FOR PATIENTS WITH NO RESIDUAL DISEASE (pCR) - (PHASE II): PT/INR/PTT =< 1.5 x ULN OR if patient is receiving anticoagulant therapy and PT or PTT is within therapeutic range of intended use of coagulants (obtained =< 28 days prior to registration)
  • REGISTRATION - FOR PATIENTS WITH NO RESIDUAL DISEASE (pCR) - (PHASE II): Negative pregnancy test done =< 7 days prior to registration, for person of childbearing potential
  • NOTE: If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
  • RANDOMIZATION - PATIENTS WITH RESIDUAL DISEASE POST NEOADJUVANT TRATUZUMAB +/- PERTUZUMAB BASED CHEMOTHERAPY (NO pCR) - (PHASE II): Absolute neutrophil count (ANC) >= 1500/mm^3 (obtained =< 28 days prior to randomization)
  • RANDOMIZATION - PATIENTS WITH RESIDUAL DISEASE POST NEOADJUVANT TRATUZUMAB +/- PERTUZUMAB BASED CHEMOTHERAPY (NO pCR) - (PHASE II): Platelet count >= 75,000/mm^3 (obtained =< 28 days prior to randomization)
  • RANDOMIZATION - PATIENTS WITH RESIDUAL DISEASE POST NEOADJUVANT TRATUZUMAB +/- PERTUZUMAB BASED CHEMOTHERAPY (NO pCR) - (PHASE II): Hemoglobin >= 9.0 g/dL (obtained =< 28 days prior to randomization)
  • RANDOMIZATION - PATIENTS WITH RESIDUAL DISEASE POST NEOADJUVANT TRATUZUMAB +/- PERTUZUMAB BASED CHEMOTHERAPY (NO pCR) - (PHASE II): Direct bilirubin < 1.5 x upper limit of normal (ULN) (obtained =< 28 days prior to randomization)
  • RANDOMIZATION - PATIENTS WITH RESIDUAL DISEASE POST NEOADJUVANT TRATUZUMAB +/- PERTUZUMAB BASED CHEMOTHERAPY (NO pCR) - (PHASE II): Aspartate transaminase (AST) =< 3 x ULN (obtained =< 28 days prior to randomization)
  • RANDOMIZATION - PATIENTS WITH RESIDUAL DISEASE POST NEOADJUVANT TRATUZUMAB +/- PERTUZUMAB BASED CHEMOTHERAPY (NO pCR) - (PHASE II): Creatinine =< 2 x ULN (obtained =< 28 days prior to randomization)
  • RANDOMIZATION - PATIENTS WITH RESIDUAL DISEASE POST NEOADJUVANT TRATUZUMAB +/- PERTUZUMAB BASED CHEMOTHERAPY (NO pCR) - (PHASE II): PT/INR/PTT =< 1.5 x ULN OR if patient is receiving anticoagulant therapy and PT or PTT is within therapeutic range of intended use of coagulant (obtained =< 28 days prior to randomization)
  • RANDOMIZATION - PATIENTS WITH RESIDUAL DISEASE POST NEOADJUVANT TRATUZUMAB +/- PERTUZUMAB BASED CHEMOTHERAPY (NO pCR) - (PHASE II): Completed last cycle of chemotherapy >= 90 days prior to randomization
  • NOTE: Prior to randomization, patients must not receive >= 6 cycles of T-DM1 maintenance therapy after surgery
  • RANDOMIZATION - PATIENTS WITH RESIDUAL DISEASE POST NEOADJUVANT TRATUZUMAB +/- PERTUZUMAB BASED CHEMOTHERAPY (NO pCR) - (PHASE II): Have residual disease with >= 1 cm residual tumor in the breast (>= ypT1c) and/or persistent lymph node positivity after trastuzumab +/- pertuzumab based neoadjuvant chemotherapy
  • RANDOMIZATION - PATIENTS WITH RESIDUAL DISEASE POST NEOADJUVANT TRATUZUMAB +/- PERTUZUMAB BASED CHEMOTHERAPY (NO pCR) - (PHASE II): Adequate tissue specimens from both pre-treatment biopsy and surgery must be submitted. Adequate tissue samples defined as core needle biopsy or incisional biopsy or excisional samples that can provide >= 3 core needle biopsies with at least 14G needle with 12 unstained sections of 5 micron thickness
  • NOTE: Fine needle aspiration (FNA) sample alone is not sufficient
  • RANDOMIZATION - PATIENTS WITH RESIDUAL DISEASE POST NEOADJUVANT TRATUZUMAB +/- PERTUZUMAB BASED CHEMOTHERAPY (NO pCR) - (PHASE II): Negative pregnancy test done =< 7 days prior to randomization, 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
  • RANDOMIZATION - PATIENTS WITH RESIDUAL DISEASE POST NEOADJUVANT TRATUZUMAB +/- PERTUZUMAB BASED CHEMOTHERAPY (NO pCR) - (PHASE II): ECOG performance status (PS) 0, 1, 2
  • RANDOMIZATION - PATIENTS WITH RESIDUAL DISEASE POST NEOADJUVANT TRATUZUMAB +/- PERTUZUMAB BASED CHEMOTHERAPY (NO pCR) - (PHASE II): Willing to employ adequate contraception from the time of randomization through 6 months after the final vaccine cycle

Who cannot join

  • 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
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  • 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
  • PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): Receiving any other investigational agent
  • PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): Other active malignancy at time of pre-registration or =< 3 years prior to preregistration
  • EXCEPTIONS: Non-melanoma skin cancer or carcinoma-in-situ (e.g. of cervix, prostate)
  • NOTE: If there is a history of prior malignancy, they must not be receiving other specific treatment (cytotoxics, monoclonal antibodies, small molecule inhibitors) for their cancer
  • PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): Known history of active autoimmune disease that has required systemic treatment in the =< 30 days (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs) prior to pre-registration. NOTE: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment. Patients with vitiligo, Graves disease, or psoriasis not requiring systemic treatment within the past 30 days are not excluded. Patients with Celiac disease controlled with diet modification are not excluded
  • PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): Any prior hypersensitivity or adverse reaction to granulocyte-macrophage colony stimulating factor (GM-CSF)
  • PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): History of trastuzumab-related cardiac toxicity requiring interruption or discontinuation of therapy, even if left ventricular ejection fraction (LVEF) fully recovered
  • PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): Baseline LVEF < 50%
  • PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): Failure to fully recover from acute, reversible effects of prior chemotherapy regardless of interval since last treatment
  • PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): History of myocardial infarction =< 168 days (6 months) prior to pre-registration, or congestive heart failure requiring use of ongoing maintenance therapy for life threatening ventricular arrhythmias
  • PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): Patients who received tamoxifen or raloxifene or another agent for prevention of breast cancer =< 2 months prior to pre-registration

Trial locations and contacts

30 sites in 1 country.

30 sites in 1 country

United States30 sites, 15 recruiting

  • Emory University Hospital/Winship Cancer Institute

    Atlanta, Georgia, 30322

    Keerthi Gogineni, keerthi.gogineni@emory.edu

    Keerthi Gogineni

    Not yet recruiting

  • University of Maryland/Greenebaum Cancer Center

    Baltimore, Maryland, 21201

    Katherine H. Tkaczuk, ktkaczuk@umm.edu

    Katherine H. Tkaczuk

    Not yet recruiting

  • City of Hope Comprehensive Cancer Center

    Duarte, California, 91010

    Withdrawn

  • Essentia Health NCI Community Oncology Research Program

    Duluth, Minnesota, 55805

    Withdrawn

  • Marshfield Medical Center-EC Cancer Center

    Eau Claire, Wisconsin, 54701

    ACCRU Operations, 507-538-7448, ACCRU@mayo.edu

    Arlene A. Gayle

    Not yet recruiting

  • Inova Fairfax Hospital

    Falls Church, Virginia, 22042

    Withdrawn

  • University of Florida Health Science Center - Gainesville

    Gainesville, Florida, 32610

    Karen C. Daily, karen.daily@medicine.ufl.edu

    Karen C. Daily

    Recruiting

  • Saint Vincent Hospital Cancer Center Green Bay

    Green Bay, Wisconsin, 54301

    Withdrawn

  • Mayo Clinic in Florida

    Jacksonville, Florida, 32224-9980

    ACCRU Operations, 507-538-7448, ACCRU@mayo.edu

    Saranya Chumsri

    Recruiting

  • UC San Diego Moores Cancer Center

    La Jolla, California, 92093

    ACCRU Operations, 507-538-7459, ACCRU@mayo.edu

    Sarah G. Boles

    Not yet recruiting

  • Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center

    Lebanon, New Hampshire, 03756

    Laurie Balch, 306-650-2809, cancer.research.nurse@hitchcock.org

    Mary D. Chamberlin

    Recruiting

  • Dean Hematology and Oncology Clinic

    Madison, Wisconsin, 53717

    Withdrawn

  • Middlesex Hospital

    Middletown, Connecticut, 06457

    Withdrawn

  • Vanderbilt University/Ingram Cancer Center

    Nashville, Tennessee, 37232

    ACCRU Operations, 507-538-7448, ACCRU@mayo.edu

    Vandana G. Abramson

    Not yet recruiting

  • University Medical Center New Orleans

    New Orleans, Louisiana, 70112

    Jyotsna Fuloria, jyotsna.fuloria@lcmchealth.org

    Jyotsna Fuloria

    Recruiting

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68198

    Anita Rogic, 402-559-5524, arogic@unmc.edu

    Jairam Krishnamurthy, MD

    Recruiting

  • Illinois CancerCare-Peoria

    Peoria, Illinois, 61615

    Withdrawn

  • FirstHealth of the Carolinas-Moore Regional Hospital

    Pinehurst, North Carolina, 28374

    Charles S. Kuzma, 507-538-7448, ckuzma@firsthealth.org

    Charles S. Kuzma

    Recruiting

  • Mayo Clinic in Rochester

    Rochester, Minnesota, 55905

    ACCRU Operations, 507-538-7448, ACCRU@mayo.edu

    Kathryn J. Ruddy

    Recruiting

  • Coborn Cancer Center at Saint Cloud Hospital

    Saint Cloud, Minnesota, 56303

    Withdrawn

  • Guthrie Medical Group PC-Robert Packer Hospital

    Sayre, Pennsylvania, 18840

    Withdrawn

  • Mayo Clinic in Arizona

    Scottsdale, Arizona, 85259

    ACCRU Operations, 507-538-7448, ACCRU@mayo.edu

    Brenda J. Ernst

    Recruiting

  • Siouxland Regional Cancer Center

    Sioux City, Iowa, 51101

    Withdrawn

  • Washington University School of Medicine

    St Louis, Missouri, 63110

    Withdrawn

  • Banner University Medical Center - Tucson

    Tucson, Arizona, 85719

    Pavani Chalasani, 520-626-7725, pchalasani@uacc.arizona.edu

    Pavani Chalasani

    Recruiting

  • University of Arizona Cancer Center-North Campus

    Tucson, Arizona, 85719

    ACCRU Operations, 507-538-7448, ACCRU@mayo.edu

    Pavani Chalasani

    Recruiting

  • Carle Cancer Center NCI Community Oncology Research Program

    Urbana, Illinois, 61801

    Withdrawn

  • Lexington Medical Center

    West Columbia, South Carolina, 29169

    Withdrawn

  • Cleveland Clinic Florida

    West Palm Beach, Florida, 33401

    Withdrawn

  • Yuma Regional Medical Center

    Yuma, Arizona, 85364

    Withdrawn

Other trials in United States

About this study

Official title: Phase II Trial to Evaluate Immune-Related Biomarkers for Pathological Response in Stage II-III HER2-Positive Breast Cancer Receiving Neoadjuvant Chemotherapy With Subsequent Randomization to Multi-Epitope HER2 Vaccine vs. Placebo in Patients With Residual Disease Post-Neoadjuvant Chemotherapy

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To evaluate invasive disease free survival (iDFS) of multi-epitope HER2 vaccine versus (vs.) placebo in combination with ado-trastuzumab emtansine (TTT-DM1) in patients with stage II-III HER2 positive (+) breast cancer (BC) with residual disease post-neoadjuvant chemotherapy.

II. To evaluate the safety of multi-epitope HER2 vaccine given concurrently with ado-trastuzumab emtansine (T-DM1) maintenance therapy.

SECONDARY OBJECTIVES:

  1. To evaluate immunogenicity of multi-epitope HER2 vaccine in combination with T-DM1 maintenance therapy.

II. To evaluate the immune-related tissue and blood biomarkers for complete pathological response in patients with stage II-III HER2+ BC receiving neoadjuvant chemotherapy.

CORRELATIVE RESEARCH OBJECTIVES:

  1. To determine host immune factors which are critical to prevent disease recurrence in HER2+ BC patients.

Ia. To determine if the development of T cell immunity, as assessed by IFN-gamma enzyme-linked immunospot (ELISpot), to HER2 correlates with improved iDFS.

Ib. To determine the distribution of the helper T cell response among helper T cell differentiation states.

Ic. To determine if augmenting CD4 helper T cell immunity augments HER2-specific antibody immunity induced by trastuzumab.

Id. To determine if human leukocyte antigen (HLA) genotypes are associated with antibody responses before and after neoadjuvant therapy and vaccination.

Ie. To determine gene expression levels in tumors from patients who did not achieve complete pathological response (pCR) that are associated with recurrence.

II. To determine tumor intrinsic genotyping and phenotyping features associated with therapeutic failure to HER2 immune-based approaches.

IIa. To determine whether HER2 monoclonal antibody therapy induces HER2 loss and modulation of HER2-specific adaptive immune responses.

IIb. To determine loss-of-function mutations in breast tumor that associate with lack of pCR and lack of immune response to HER2+ neoadjuvant treatment.

OUTLINE:

pCR AFTER NEOADJUVANT CHEMOTHERAPY AND SURGERY: Patients receive standard of care maintenance therapy with trastuzumab and pertuzumab for 1 year in the absence of disease progression or unacceptable toxicity.

NO pCR AFTER NEOADJUVANT CHEMOTHERAPY AND SURGERY: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive standard of care maintenance therapy with trastuzumab emtansine and receive TPIV100 intradermally (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.

ARM 2: Patients receive standard of care maintenance therapy with trastuzumab emtansine and receive placebo intradermally (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.

Being tested
Multi-epitope HER2 Peptide Vaccine TPIV100, Pertuzumab, Placebo Administration, Sargramostim, Trastuzumab
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Multi-epitope HER2 Peptide Vaccine TPIV100Biological

    Also called HER2/Neu Peptide Vaccine TPIV100, Peptide Vaccine TPIV100, TPIV 100, TPIV-100

    Given ID

  • PertuzumabBiological

    Also called 2C4, 2C4 Antibody, HS627, MoAb 2C4

    permitted at physician's discretion

  • Placebo AdministrationOther

    Given ID

  • SargramostimBiological

    Also called 23-L-Leucinecolony-Stimulating Factor 2, DRG-0012, Leukine, Prokine

    Given ID

  • TrastuzumabBiological

    Also called ABP 980, ALT02, Anti-c-ERB-2, Anti-c-erbB2 Monoclonal Antibody

    therapy are at the discretion of the treating physicians

  • Trastuzumab EmtansineBiological

    Also called Ado Trastuzumab Emtansine, ADO-Trastuzumab Emtansine, Kadcyla, PRO132365

    at the discretion of the treating physicians.

Study groups in NCT04197687
Study groupRoleWhat they receive
Arm I - No pCR (trastuzumab emtansine, TPIV100, sargramostim)ExperimentalPatients 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.
Receives: Biological: Multi-epitope HER2 Peptide Vaccine TPIV100; Biological: Sargramostim; Biological: Trastuzumab Emtansine
Arm II - No pCR (trastuzumab emtansine, placebo, sargramostim)Placebo comparatorPatients 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.
Receives: Other: Placebo Administration; Biological: Sargramostim; Biological: Trastuzumab Emtansine
Treatment (pCR)ExperimentalPatients receive standard of care maintenance therapy with trastuzumab and pertuzumab for 1 year in the absence of disease progression or unacceptable toxicity.
Receives: Biological: Pertuzumab; Biological: Trastuzumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (5)

  1. Overall survival

    defined as the time from randomization to the date of death due to any cause. Patients who are lost to follow-up for OS will be censored at the date the subject was last known to be alive

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

  2. Incidence of adverse events (AEs)

    Will be assessed according to Common Terminology Criteria for Adverse Events 5.0 and defined as adverse events that are classified as either unrelated, unlikely to be related, possibly, probably, or definitely related to the study treatment. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed by primary disease site to determine toxicity patterns. Frequency tables will be generated to summarize the occurrence of treatment-related AE's by treatment arms. Comparisons of the rates of individual AE's will be done using tests of proportions such as Fisher's exact test or Chi-squared test. Additional analysis will use the Cochran-Mantel-Haenszel chi-squared test with study stratification factors.

    Measured: Up to 24 months

  3. Immunogenicity assessment

    To evaluate immunogenicity of multi-epitope HER2 vaccine in combination with T-DM1 maintenance therapy.

    Measured: Up to 5 years

  4. Complete pathological response

    Will be assessed using immune-related tissue and blood biomarkers.

    Measured: Baseline

  5. Vaccine induced HER2-specific T cell responses

    Will be defined as a 2-fold or greater increase in HER2-specific antibody concentration from pre-treatment levels at any point during treatment or HER2-specific antibodies above the lower limit of detection at any point during treatment if pre-treatment levels were non-detectable. Antibody response frequency at the post-treatment initiation time points will be compared among arms using a chi-squared test. Antibody response magnitude at the post-treatment initiation time point will be compared among arms using an analysis of variance F-test followed by Tukey pairwise comparisons between pairs of arms. Likelihood of antibody response at the post-treatment initiation time point will be compared among arms using logistic regression (the dependent variable is antibody response [yes/no] at the post-treatment initiation time point; the independent variables are the antibody response [yes/no] at the pre-treatment time point and a categorical variable capturing arm).

    Measured: Baseline up to 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Dec 2019
  2. Study start20 Feb 2020
  3. Primary completion15 Jan 2025 (estimated)
  4. Study completion15 Jan 2025 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Care provider
Enrolment
480 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04197687
Sponsor's protocol ID
MC1835-ACCRU-BR-1701
Other IDs
NCI-2019-08038, MC1835-ACCRU-BR-1701, P30CA015083
Status last verified
May 2023
First submitted
5 Dec 2019
Last updated
18 Dec 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

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