Recruiting

Phase 2

TPIV100 & SargramostimTPIV100 and Sargramostim for the Treatment of HER2 Positive, Stage II-III Breast Cancer in Patients With Residual Disease After Chemotherapy and Surgery

Sponsor:

Academic and Community Cancer Research United

Code:

NCT04197687

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

Eligibility Criteria

Sex: Female

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Multi-epitope HER2 Peptide Vaccine TPIV100

Pertuzumab

Placebo Administration

Sargramostim

Trastuzumab

Study Details

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

Study ID

NCT04197687

Start date

Feb 20, 2020

Status verified date

May, 2023

Completion date

Jan 15, 2025

Anticipated

Primary completion date

Jan 15, 2025

Anticipated

Eligibility Criteria

Sex: Female

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

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)
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

Exclusion Criteria:

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
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

Study Design

Enrollment

480 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

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

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.

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

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.

experimental: Treatment (pCR)

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

Interventions

Multi-epitope HER2 Peptide Vaccine TPIV100

Given ID

Pertuzumab

permitted at physician's discretion

Placebo Administration

Given ID

Sargramostim

Given ID

Trastuzumab

therapy are at the discretion of the treating physicians

Trastuzumab Emtansine

at the discretion of the treating physicians.

Primary outcome measure

Invasive disease-free survival (iDFS) between the 2 arms [ Time Frame: From time of randomization to recurrence, invasive breast cancer or death, assessed up to 5 years ]

Central Contacts and Locations

Locations

Mayo Clinic in Arizona

Recruiting

Scottsdale, Arizona, United States, 85259

Contacts

ACCRU Operations

507-538-7448 ACCRU@mayo.edu

Principal Investigator:

Brenda J. Ernst

Banner University Medical Center - Tucson

Recruiting

Tucson, Arizona, United States, 85719

Contacts

Pavani Chalasani

520-626-7725 pchalasani@uacc.arizona.edu

Principal Investigator:

Pavani Chalasani

University of Arizona Cancer Center-North Campus

Recruiting

Tucson, Arizona, United States, 85719

Contacts

ACCRU Operations

507-538-7448 ACCRU@mayo.edu

Principal Investigator:

Pavani Chalasani

University of Florida Health Science Center - Gainesville

Recruiting

Gainesville, Florida, United States, 32610

Contacts

Karen C. Daily

karen.daily@medicine.ufl.edu

Principal Investigator:

Karen C. Daily

Mayo Clinic in Florida

Recruiting

Jacksonville, Florida, United States, 32224-9980

Contacts

ACCRU Operations

507-538-7448 ACCRU@mayo.edu

Principal Investigator:

Saranya Chumsri

University Medical Center New Orleans

Recruiting

New Orleans, Louisiana, United States, 70112

Contacts

Jyotsna Fuloria

jyotsna.fuloria@lcmchealth.org

Principal Investigator:

Jyotsna Fuloria

Mayo Clinic in Rochester

Recruiting

Rochester, Minnesota, United States, 55905

Contacts

ACCRU Operations

507-538-7448 ACCRU@mayo.edu

Principal Investigator:

Kathryn J. Ruddy

University of Nebraska Medical Center

Recruiting

Omaha, Nebraska, United States, 68198

Contacts

Anita Rogic

402-559-5524 arogic@unmc.edu

Principal Investigator:

Jairam Krishnamurthy, MD

Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center

Recruiting

Lebanon, New Hampshire, United States, 03756

Contacts

Laurie Balch

306-650-2809 cancer.research.nurse@hitchcock.org

Principal Investigator:

Mary D. Chamberlin

FirstHealth of the Carolinas-Moore Regional Hospital

Recruiting

Pinehurst, North Carolina, United States, 28374

Contacts

Charles S. Kuzma

507-538-7448 ckuzma@firsthealth.org

Principal Investigator:

Charles S. Kuzma

More Information

Sponsor

Academic and Community Cancer Research United

Last update posted

Dec 18, 2023

Last verified

May, 2023

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Academic and Community Cancer Research United on 2023-12-18.