Clinical Trials /

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

NCT04197687

Description:

This phase II trial studies how well TPIV100 and sargramostim work in treating patients with HER2 positive, stage II-III breast cancer that has remained after chemotherapy and 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.

Related Conditions:
  • Breast Adenocarcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: MC1835
  • SECONDARY ID: NCI-2019-08038
  • SECONDARY ID: MC1835
  • SECONDARY ID: P30CA015083
  • NCT ID: 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
  • Stage IIIA Breast Cancer AJCC v7
  • Stage IIIB Breast Cancer AJCC v7
  • Stage IIIC Breast Cancer AJCC v7

Interventions

DrugSynonymsArms
Pertuzumab2C4, 2C4 Antibody, MoAb 2C4, Monoclonal Antibody 2C4, Omnitarg, Perjeta, rhuMAb2C4, RO4368451Treatment (pCR)
Sargramostim23-L-Leucinecolony-Stimulating Factor 2, DRG-0012, Leukine, Prokine, rhu GM-CFS, Sagramostim, SargramostatinArm I - No pCR (trastuzumab emtansine, TPIV100, sargramostim)
TrastuzumabABP 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, 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-dkst, Trastuzumab-dttb, Trastuzumab-pkrb, Trastuzumab-QYYP, TrazimeraTreatment (pCR)
Trastuzumab EmtansineAdo Trastuzumab Emtansine, ADO-Trastuzumab Emtansine, Kadcyla, PRO132365, RO5304020, T-DM1, Trastuzumab-DM1, Trastuzumab-MCC-DM1, Trastuzumab-MCC-DM1 Antibody-Drug Conjugate, Trastuzumab-MCC-DM1 ImmunoconjugateArm I - No pCR (trastuzumab emtansine, TPIV100, sargramostim)
Vaccine TherapyArm I - No pCR (trastuzumab emtansine, TPIV100, sargramostim)

Purpose

This phase II trial studies how well TPIV100 and sargramostim work in treating patients with HER2 positive, stage II-III breast cancer that has remained after chemotherapy and 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.

Detailed Description

      PRIMARY OBJECTIVES:

      I. 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:

      I. 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:

      I. 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 II: 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.

      After completion of study treatment, patients with pCR are followed up at 30 days and 24
      months. Patients with no pCR followed up at 30 days and at 3, 4, 12, 13, and 24 months. All
      patients are then followed up every 6 months for up to 5 years.
    

Trial Arms

NameTypeDescriptionInterventions
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.
  • Sargramostim
  • Trastuzumab Emtansine
  • Vaccine Therapy
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.
  • Sargramostim
  • 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.
  • Pertuzumab
  • Trastuzumab

Eligibility Criteria

        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): Patients must have
             adequate pretreatment biopsy sample available

               -  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 randomization, patients must not receive >= 6 cycles of T-DM1
                  maintenance therapy after surgery

          -  REGISTRATION (SAFETY LEAD-IN): Have residual disease with >= 1 cm residual tumor in
             the breast (>= ypT1c) and/or persistent lymph node positivity after trastuzumab +/-
             pertuzumab based neoadjuvant chemotherapy

          -  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 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 =< 90 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
             autoimmune disease, including type I diabetes

          -  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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

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
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Overall survival
Time Frame:From randomization to the date of death due to any cause, assessed up to 5 years
Safety Issue:
Description:
Measure:Incidence of adverse events (AEs)
Time Frame:Up to 24 months
Safety Issue:
Description: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.
Measure:Immunogenicity assessment using ELISA assays to measure the antibody response to HER2 and ELIspot assays to measure the HER2 specific T-cell response
Time Frame:Up to 5 years
Safety Issue:
Description:Assessment of immunogenicity of multi-epitope HER2 vaccine in combination with HP maintenance therapy in patients with stage II-III HER2+ BC who have residual disease after neoadjuvant chemotherapy.
Measure:Complete pathological response
Time Frame:Baseline
Safety Issue:
Description:Will be assessed using immune-related tissue and blood biomarkers.
Measure:Vaccine induced HER2-specific T cell responses
Time Frame:Baseline up to 24 months
Safety Issue:
Description: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).

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Mayo Clinic

Last Updated

December 11, 2019