Clinical Trial: NCT04266249 - My Cancer Genome

NCT04266249

Description:

This trial studies how well paclitaxel, trastuzumab, and pertuzumab work in eliminating further chemotherapy after surgery in patients with HER2-positive stage II-IIIa breast cancer who have no cancer remaining at surgery (either in the breast or underarm lymph nodes) after pre-operative chemotherapy and HER2-targeted therapy. Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Trastuzumab and pertuzumab are both a form of "targeted therapy" because they work by attaching themselves to specific molecules (receptors) on the surface of tumor cells, known as HER2 receptors. When these drugs attach to HER2 receptors, the signals that tell the cells to grow are blocked and the tumor cell may be marked for destruction by the body's immune system. Giving paclitaxel, trastuzumab, and pertuzumab may enable fewer chemotherapy drugs to be given without compromising patient outcomes compared to the usual treatment.

Related Conditions:

Invasive Breast Carcinoma

Recruiting Status:

Recruiting

Phase:

Phase 2

URL:

https://clinicaltrials.gov/show/NCT04266249

Trial Eligibility

Document

Title

Brief Title: CompassHER2-pCR: Decreasing Chemotherapy for Breast Cancer Patients After Pre-surgery Chemo and Targeted Therapy
Official Title: (CompassHER2-pCR): Preoperative THP and Postoperative HP in Patients Who Achieve a Pathologic Complete Response

Clinical Trial IDs

ORG STUDY ID: EA1181
SECONDARY ID: NCI-2019-07439
SECONDARY ID: EA1181
SECONDARY ID: EA1181
SECONDARY ID: U10CA180820
NCT ID: NCT04266249

Conditions

Anatomic Stage II Breast Cancer AJCC v8
Anatomic Stage IIA Breast Cancer AJCC v8
Anatomic Stage IIB Breast Cancer AJCC v8
Anatomic Stage IIIA Breast Cancer AJCC v8
Invasive Breast Carcinoma
Prognostic Stage II Breast Cancer AJCC v8
Prognostic Stage IIA Breast Cancer AJCC v8
Prognostic Stage IIB Breast Cancer AJCC v8
Prognostic Stage IIIA Breast Cancer AJCC v8

Interventions

Drug	Synonyms	Arms
Docetaxel	Docecad, RP56976, Taxotere, Taxotere Injection Concentrate	Arm A (pCR after surgery)
Nab-paclitaxel	ABI 007, ABI-007, Abraxane, Albumin-bound Paclitaxel, Albumin-Stabilized Nanoparticle Paclitaxel, Nanoparticle Albumin-bound Paclitaxel, Nanoparticle Paclitaxel, Paclitaxel Albumin, paclitaxel albumin-stabilized nanoparticle formulation, protein-bound paclitaxel	Arm A (pCR after surgery)
Paclitaxel	Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat	Arm A (pCR after surgery)
Pertuzumab	2C4, 2C4 Antibody, MoAb 2C4, Monoclonal Antibody 2C4, Omnitarg, Perjeta, rhuMAb2C4, RO4368451	Arm A (pCR after surgery)
Trastuzumab	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, 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, Trazimera	Arm A (pCR after surgery)
Trastuzumab Emtansine	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 B (residual invasive disease after surgery)

Purpose

Detailed Description

      PRIMARY OBJECTIVES:

      I. To determine if 3-year recurrence-free survival (RFS) is greater than 92% among clinical
      stages II or IIIa patients with HER2-positive breast cancer who achieve pathologic complete
      response (pCR) (ypT0/is ypN0) after preoperative therapy with 12 weeks of a taxane,
      trastuzumab (or Food and Drug Administration [FDA] approved biosimilar) and pertuzumab (THP x
      12).

      SECONDARY OBJECTIVES:

      I. To determine 3-year IDFS (invasive disease-free survival), DDFS (distant disease-free
      survival), DRFS (distant relapse-free survival), RFI (recurrence-free interval), OS (overall
      survival) and breast cancer-specific survival in patients who achieve pCR (and by
      pretreatment clinical stage). (Secondary Clinical Objective) II. To determine 3-year EFS
      (event-free survival) in all patients from time of study registration. (Secondary Clinical
      Objective) III. To evaluate safety and tolerability for all patients during the pre-operative
      phase and for patients who attain pCR and de-escalate therapy (Arm A) until the completion of
      post-surgery protocol assigned therapy (i.e. until the end of trastuzumab and pertuzumab [HP]
      therapy). (Secondary Clinical Objective) IV. To evaluate the association of estrogen receptor
      (ER) status in the untreated primary tumor with pathologic response and with long-term
      survival outcomes (including RFS, EFS, IDFS, DDFS, DRFS, RFI, OS, and breast cancer-specific
      survival). (Secondary Correlative Objective) V. To evaluate the associations of detection of
      circulating tumor cells (CTCs) in the blood at baseline with pCR. (Secondary Correlative
      Objective) VI. To evaluate the association of detection of CTCs in the blood at baseline,
      after 3 weeks of THP, after 12 weeks of THP (before surgery), after surgery before any
      additional therapy, and after completion of HER2-targeted therapy with RFS in patients who
      achieve pCR or not. (Secondary Correlative Objective)

      EXPLORATORY OBJECTIVES:

      I. To determine 3-year RFS, IDFS (invasive disease-free survival), DDFS (distant disease-free
      survival), DRFS (distant relapse-free survival), RFI (recurrence-free interval), OS (overall
      survival) and breast cancer-specific survival in patients who do not achieve pCR (and by
      pretreatment clinical stage). (Exploratory Clinical Objective) II. To determine the
      pathologic response to THP neoadjuvant therapy, as assessed by residual cancer burden (RCB).
      (Exploratory Clinical Objective) III. To determine the association between residual cancer
      burden (RCB) and all described standardized definitions for efficacy end points (STEEP)
      criteria outcomes. (Exploratory Clinical Objective) IV. To determine the false negative rate
      (FNR) of limited staging procedures (defined as sentinel lymph node biopsy [SLNB] plus
      removal of clipped node) in patients who undergo such procedures with a planned axillary
      lymph node dissection (ALND). (Exploratory Clinical Objective) V. To determine axillary pCR
      rates as a function of the burden of disease at presentation as determined on pre-treatment
      ultrasound (US) and the axillary staging technique (SLNB plus ensuring removal of clipped
      node versus ALND). (Exploratory Clinical Objective) VI. To evaluate the associations between
      plasma tumor cell-free deoxyribonucleic acid (DNA) (cfDNA) tumor-specific mutations (baseline
      and after therapy) with pathologic response and long-term outcomes (including RFS, EFS, IDFS,
      DDFS, DRFS, RFI, OS, and breast cancer-specific survival). (Exploratory Correlative
      Objective) VII. To evaluate the associations between tumor infiltrating lymphocytes (TILs)
      and immune activation gene signatures in the baseline tumor with pathologic response and
      long-term outcomes (including RFS, EFS, IDFS, DDFS, DRFS, RFI, OS and breast cancer-specific
      survival). (Exploratory Correlative Objective) VIII. To determine the frequency of change in
      intrinsic subtype between pretreatment tumor specimen and residual disease at the time of
      surgery. (Exploratory Correlative Objective) IX. To evaluate the associations between DNA
      copy number, DNA mutations, ribonucleic acid (RNA) expression and protein expression in the
      baseline tumor and changes from baseline to post-THP therapy with pathologic response and
      long-term outcomes (including RFS, EFS, IDFS, DDFS, DRFS, RFI, OS, and breast cancer-specific
      survival). (Exploratory Correlative Objective)

      OUTLINE:

      PRE-OPERATIVE/NEOADJUVANT THERAPY: Patients receive either paclitaxel or nab-paclitaxel
      intravenously (IV) on days 1, 8 and 15, or docetaxel IV on day 1 at the discretion of the
      treating oncologist. Patients also receive trastuzumab IV on day 1 or days 1, 8, and 15, and
      pertuzumab IV on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of
      disease progression or unacceptable toxicity.

      SURGERY: Within 42 days after last dose of neoadjuvant therapy, patients undergo standard of
      care lumpectomy and/or mastectomy.

      POST-OPERATIVE/ADJUVANT THERAPY: Patients are assigned to 1 of 2 arms.

      ARM A: Patients with pCR after surgery receive trastuzumab and pertuzumab IV on day 1.
      Treatment repeats every 21 days for up to 13 cycles in the absence of disease progression or
      unacceptable toxicity. Patients may also undergo standard of care radiation therapy and
      receive hormone therapy if appropriate.

      ARM B: Patients with remaining tumor after surgery receive standard of care trastuzumab
      emtansine for 14 doses in the absence of disease progression or unacceptable toxicity.
      Patients may also receive additional standard of care chemotherapy, as well as hormone
      therapy if appropriate.

      After completion of study treatment, patients are followed up every 3 months for 2 years,
      every 6 months for 2-5 years, then annually for 5-15 years from date of surgery.

Trial Arms

Name	Type	Description	Interventions
Arm A (pCR after surgery)	Experimental	PRE-OPERATIVE/NEOADJUVANT THERAPY: Patients receive either paclitaxel or nab-paclitaxel IV on days 1, 8 and 15, or docetaxel IV on day 1 at the discretion of the treating oncologist. Patients also receive trastuzumab IV on day 1 or days 1, 8, and 15, and pertuzumab IV on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. SURGERY: Within 42 days after last dose of neoadjuvant therapy, patients undergo standard of care lumpectomy and/or mastectomy. POST-OPERATIVE.ADJUVANT THERAPY: Patients with pCR after surgery receive trastuzumab and pertuzumab IV on day 1. Treatment repeats every 21 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity. Patients may also undergo standard of care radiation therapy and receive hormone therapy if appropriate.	Docetaxel Nab-paclitaxel Paclitaxel Pertuzumab Trastuzumab
Arm B (residual invasive disease after surgery)	Experimental	PRE-OPERATIVE/NEOADJUVANT THERAPY: Patients receive either paclitaxel or nab-paclitaxel IV on days 1, 8 and 15, or docetaxel IV on day 1 at the discretion of the treating oncologist. Patients also receive trastuzumab IV on day 1 or days 1, 8, and 15, and pertuzumab IV on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. SURGERY: Within 42 days after last dose of neoadjuvant therapy, patients undergo standard of care lumpectomy and/or mastectomy. POST-OPERATIVE/ADJUVANT THERAPY: Patients with remaining tumor after surgery receive standard of care trastuzumab emtansine for 14 doses in the absence of disease progression or unacceptable toxicity. Patients may also receive additional standard of care chemotherapy, as well as hormone therapy if appropriate.	Docetaxel Nab-paclitaxel Paclitaxel Pertuzumab Trastuzumab Trastuzumab Emtansine

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of
             0 or 1

          -  Patient must have histologically confirmed HER2-positive primary invasive breast
             carcinoma, determined by local testing. The tumor must have either HER2 IHC result of
             3+ or HER2/CEP17 ratio > 2 with > 4.0 HER2 signals per cell by ISH. Tumors with
             HER2/CEP17 ISH ratio < 2 are ineligible, even if HER2 copy number is > 6, unless HER2
             IHC result is 3+.

          -  Patients hormone receptor (estrogen receptor [ER] and progesterone receptor [PR])
             status must be known and will be determined by local testing. Patients with either
             hormone receptor -positive or hormone receptor- negative HER2-positive breast cancer
             are eligible

          -  Patients must have AJCC 8th Edition stage II or IIIa according to anatomic staging
             table at diagnosis

               -  Patients without nodal involvement (cN0) are eligible if T size > 2.0 cm (T2-3)

               -  Patients with nodal involvement (cN1-2) are eligible if T1-3

               -  Patients with clinical T4 or N3 disease are not eligible

          -  Patient must be willing and able (i.e., have no contraindication) to receive standard
             adjuvant therapy, consisting of HER2-directed therapy, radiation (if indicated) and
             endocrine therapy (if ER+) if achieving pCR at surgery

          -  Patient with bilateral invasive breast cancers are eligible if both cancers are
             HER2-positive (as defined in 3.1.3) at least one meets protocol eligibility and
             neither cancer renders the patient ineligible (i.e. per eligibility 3.1.5)

          -  Patients with multiple ipsilateral invasive tumors are eligible as long as all tumors
             are HER2-positive, and at least one tumor focus meets eligibility criteria (per
             eligibility 3.1.5). Multiple lesions that appear part of the same index tumor do not
             require additional biopsy/HER2 testing. Multiple lesions that appear part of the same
             index tumor do not require additional biopsy/HER2 testing. However, even if biopsy is
             not deemed necessary, consideration should be given to placing a clip in any lesion
             that is 1 cm or further from the primary tumor to ensure that all tumor is removed at
             surgery AND that the pathologist can locate all primary sites of tumor to assess
             pathologic response at surgery.

          -  Patients with a history of other non-breast malignancies are eligible if they have
             been disease-free for at least 5 years, and are deemed by the investigator to be at
             low risk for recurrence of that malignancy.

               -  Patients with the following cancers are eligible if diagnosed and treated within
                  the past 5 years: cervical cancer in situ, basal cell or squamous cell carcinoma
                  of the skin, and localized papillary or follicular thyroid cancer who have
                  completed recommended treatment including surgery. Patients with any other
                  cancers within the last 5 years are ineligible.

          -  Patents must have a left ventricular ejection fraction (LVEF) within normal
             institutional parameters (or > 50%)

          -  Patients must not have > grade 1 peripheral neuropathy of any etiology.

          -  Patients must have a bilateral mammogram and a diagnostic breast ultrasound [on the
             side of the cancer(s)] (with or without breast MRI) performed at screening. An
             axillary ultrasound on the side of the cancer(s) is also required. However, if a
             patient has a negative axillary physical exam and a baseline MRI without suspicious
             lymph nodes performed before axillary ultrasound, axillary ultrasound may be omitted.
             Comprehensive breast and axillary imaging must be performed within 42 days of
             registration (i.e. the patient's mammogram/ breast ultrasound /axillary ultrasound OR
             their breast MRI).

          -  Baseline imaging of the ipsilateral axilla by ultrasound or breast MRI is mandatory.
             For subjects with axillary lymph node(s) suspicious on clinical exam or imaging,
             patient must be willing to have a needle aspiration or core biopsy to determine the
             presence of metastatic disease in the lymph nodes. A clip must be placed in the
             involved axillary lymph node. (If there are more than 1 suspicious axillary nodes,
             only one clipped node is required).

          -  Patient of childbearing potential and sexually active patients must use accepted and
             effective method(s) of contraception or to abstain from sexual intercourse for the
             duration of their participation in the study and for 7 months after the last dose of
             study treatment.

          -  Patient must be willing and able to sign informed consent

          -  Leukocytes >= 3,000/mcL (obtained =< 28 days prior to protocol registration)

          -  Absolute neutrophil count >= 1,500/mcL (obtained =< 28 days prior to protocol
             registration)

          -  Platelets >= 100,000/mcL (obtained =< 28 days prior to protocol registration)

          -  Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (obtained =< 28
             days prior to protocol registration)

          -  Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
             =< 2.5 x institutional ULN (obtained =< 28 days prior to protocol registration)

          -  Creatinine =< 1.5 x institutional ULN (obtained =< 28 days prior to protocol
             registration)

          -  Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral
             therapy with undetectable viral load within 6 months are eligible for this trial

          -  For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral
             load must be undetectable on suppressive therapy, if indicated

          -  Patients with a history of hepatitis C virus (HCV) infection must have been treated
             and cured. For patients with HCV infection who are currently on treatment, they are
             eligible if they have an undetectable HCV viral load

        Exclusion Criteria:

          -  Patients must not have impaired decision-making capacity

          -  Patient must not have a history of any prior (ipsilateral or contralateral) invasive
             breast cancer

               -  One exception: a patient with a history of T1N0 triple negative breast cancer
                  diagnosed more than 10 years earlier, who remains disease free is eligible

          -  Patient must not have prior ipsilateral ductal breast carcinoma in situ (DCIS).
             Patients with prior lobular breast carcinoma in situ (LCIS), atypical hyperplasia,
             other high risk benign lesions or contralateral DCIS (without evidence of
             microinvasion) are eligible

               -  NOTE: Patients currently receiving endocrine therapy for prior contralateral DCIS
                  are eligible

          -  Patient must not have stage IV (metastatic) breast cancer

               -  Staging studies (computed tomography [CT] chest/abdomen/pelvis and a bone scan or
                  positron emission tomography [PET]-CT scan) are required for stage III disease or
                  those with abnormal baseline liver function tests (LFTs), symptoms (e.g. new bone
                  pain) or abnormal physical exam findings (National Comprehensive Cancer Network
                  [NCCN] guidelines version [V]1.2019)

          -  Patient must not have T4 and/or N3 disease, including inflammatory breast cancer

          -  Patient must not have any prior treatment for the current breast cancer, including
             surgery, chemotherapy, hormonal therapy, radiation or experimental therapy

          -  Patients must not have > grade 1 peripheral neuropathy of any etiology

          -  Patient must not have a concurrent serious medical condition that would preclude
             completion of study therapy. For example, uncontrolled hypertension (systolic > 180 mm
             Hg and/or diastolic > 100 mm Hg) or clinically significant (i.e. active)
             cardiovascular disease: cerebrovascular accident/stroke or myocardial infarction
             within 6 months prior to registration, unstable angina, congestive heart failure (CHF)
             or serious cardiac arrhythmia requiring medication and other concurrent serious
             diseases that may interfere with planned treatment

          -  Patient must not be pregnant or breast-feeding due to the potential harm to an unborn
             fetus and possible risk for adverse events in nursing infants with the treatment
             regimens being used. Patients must also not expect to conceive from the time of
             registration, while on study treatment, and until at least 7 months after the last
             dose of study treatment. All patients of childbearing potential must have a blood test
             or urine study within 14 days prior to registration to rule out pregnancy

               -  All patients of childbearing potential is anyone, regardless of sexual
                  orientation or whether they have undergone tubal ligation, who meets the
                  following criteria: 1) has achieved menarche at some point, 2) has not undergone
                  a hysterectomy or bilateral oophorectomy; or 3) has not been naturally
                  postmenopausal for at least 24 consecutive months (i.e., has had menses at any
                  time in the preceding 24 consecutive months)

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

Primary Outcome Measures

Measure:	Recurrence-free survival (RFS)
Time Frame:	Up to 3 years after end of treatment
Safety Issue:
Description:	Events include recurrence of ipsilateral invasive breast tumor, recurrence of locoregional invasive breast tumor, and distant recurrence. Survival curve estimated using Kaplan-Meier method in the overall analysis population and by pretreatment clinical stage and estrogen receptor (ER) status. Greenwood method will be used to estimate the 95% confidence interval for 3-year rate.

Secondary Outcome Measures

Measure:	Invasive disease-free survival (IDFS)
Time Frame:	Up to 3 years after the end of treatment
Safety Issue:
Description:	Events include recurrence of ipsilateral invasive breast tumor, recurrence of locoregional invasive breast tumor, distant recurrence, contralateral invasive breast cancer, and second primary non-breast invasive cancer (other than squamous or basal cell skin cancer). Survival curve estimated using Kaplan-Meier method in the overall analysis population and by pretreatment clinical stage and ER status. The analysis will be descriptive and there will be no statistical test.

Measure:	Distant disease-free survival (DDFS)
Time Frame:	Up to 3 years after the end of treatment
Safety Issue:
Description:	Events include distant recurrence and second primary non-breast invasive cancer (other than squamous or basal cell skin cancer). Survival curve estimated using Kaplan-Meier method in the overall analysis population and by pretreatment clinical stage and ER status. The analysis will be descriptive and there will be no statistical test.

Measure:	Distant relapse-free survival (DRFS)
Time Frame:	U to 3 years after the end of treatment
Safety Issue:
Description:	Survival curve estimated using Kaplan-Meier method in the overall analysis population and by pretreatment clinical stage and ER status. The analysis will be descriptive and there will be no statistical test.

Measure:	Recurrence-free interval (RFI)
Time Frame:	Up to 3 years after the end of treatment
Safety Issue:
Description:	Survival curve estimated using Kaplan-Meier method in the overall analysis population and by pretreatment clinical stage and ER status. The analysis will be descriptive and there will be no statistical test.

Measure:	Overall survival (OS)
Time Frame:	From date of surgery until the date of death from any cause, assessed up to 3 years after the end of treatment
Safety Issue:
Description:	Survival curve estimated using Kaplan-Meier method in the overall analysis population and by pretreatment clinical stage and ER status. The analysis will be descriptive and there will be no statistical test.

Measure:	Event-free survival (EFS)
Time Frame:	Up to 3 years after the end of treatment
Safety Issue:
Description:	Survival curve estimated using Kaplan-Meier method in the overall analysis population and by pretreatment clinical stage and ER status. The analysis will be descriptive and there will be no statistical test.

Measure:	Incidence of adverse events (AEs)
Time Frame:	Up to 1 week after cycle 4 (all patients) and/or up to cycle 13 post-surgery (Arm A only) (each cycle is 21 days)
Safety Issue:
Description:	Will be graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0. All treatment-emergent and baseline adverse events and hematological/biochemical toxicities based on laboratory measurements, as well as drug related AEs, will be summarized by NCI CTCAE v5.0 worst grade. The incidence of deaths and treatment-emergent serious adverse events (defined as number of patients experiencing the AE divided by all treated patients) will be summarized using binominal proportions and binomial exact 95% confidence intervals. The incidence of adverse events leading to discontinuation of protocol therapy will be summarized and listed as well.

Details

Phase:	Phase 2
Primary Purpose:	Interventional
Overall Status:	Recruiting
Lead Sponsor:	ECOG-ACRIN Cancer Research Group

Last Updated

July 23, 2021

Clinical Trials /

CompassHER2-pCR: Decreasing Chemotherapy for Breast Cancer Patients After Pre-surgery Chemo and Targeted Therapy