Clinical Trials /

Markers to Evaluate the Efficacy of PH-based Regimen as a Neoadjuvant Therapy for Operable HER2 Positive Breast Cancer

NCT04281641

Description:

This study is to explore the markers in early prediction of the efficacy of pre-operative pertuzumab plus trastuzumab (PH) combined with chemotherapy for early stage or locally advanced human epidermal growth factor receptor-2 (HER-2) positive primary breast cancer.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

N/A

URL:

https://clinicaltrials.gov/show/NCT04281641

Trial Eligibility

Document

Title

  • Brief Title: Markers to Evaluate the Efficacy of PH-based Regimen as a Neoadjuvant Therapy for Operable HER2 Positive Breast Cancer
  • Official Title: Gene Expression Assays and 68 Ga-Affibody HER-2 Imaging PET in Predicting Response to Treatment With Trastuzumab and Pertuzumab Before Surgery in Chinese Patients With HER2 Positive Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: SCHBCC-NO28
  • NCT ID: NCT04281641

Conditions

  • HER2-positive Breast Cancer

Purpose

This study is to explore the markers in early prediction of the efficacy of pre-operative pertuzumab plus trastuzumab (PH) combined with chemotherapy for early stage or locally advanced human epidermal growth factor receptor-2 (HER-2) positive primary breast cancer.

Detailed Description

      This study is to evaluate the correlation between early changes in multiple markers and
      pathological complete response in breast and lyphm nodes (tpCR) in patients with
      HER2-positive breast cancer receiving carboplatin, docetaxel and trastuzumab plus pertuzumab
      (TCHP) pre-operatively. The markers would be examined by gene expression assays,
      fluorodeoxyglucose positron emission tomography (18F-FDG-PET), 68 Ga-Affibody HER-2 Imaging
      PET, and organoid drug sensitivity test. Approximately 94 patients were treated with PH-based
      neoadjuvant therapy followed by surgery, and would complete 1 year of PH-based regimen in the
      adjuvant setting. The primary endpoint is the percent change of SUVmax from baseline to Day
      15 (after the first cycle of anti HER-2 targeting drug treatment) on FDG PET and HER-2
      imagining PET in correlation with pathological complete response (pCR) in patients treated
      with preoperative pertuzumab and trastuzumab. pCR was defined as no viable invasive cancer in
      breast and axilla by local pathology review.

Trial Arms

NameTypeDescriptionInterventions
TCHPExperimentalNeoadjuvant Therapy (Cycles 1-7): Cycle 1: Pertuzumab (840mg loading dose, 420mg maintenance dose) + Trastuzumab (8mg/kg loading dose, 6-mg/kg maintenance dose) Cycle 2-7: Pertuzumab (840mg loading dose, 420mg maintenance dose) + Trastuzumab (8mg/kg loading dose, 6-mg/kg maintenance dose) + followed by carboplatin at target area under the plasma concentration-time curve (AUC) 6 and docetaxel at a starting dose of 75 mg/m2 then to 60mg/m2 (q3w). Adjuvant Therapy:patients would complete 1 year of PH-based regimen in the adjuvant setting. Patients are assessed by [18F]Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) and 68Ga-Affibody HER-2 Imaging PET. Besides, the changes of biomarkers would be examined by gene sequencing and organoid drug sensitivity test.

    Eligibility Criteria

            Inclusion Criteria:

          1. Female or male, presenting for the first time with operable breast cancer, who had not
             received any previous treatment for an invasive malignancy.

          2. Primary tumor greater than (>) 2 cm in diameter.

          3. Age ≥ 18 years and < 70 years.

          4. Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to
             (</=) 1.

          5. Baseline left ventricular ejection fraction (LVEF) greater than or equal to (>/=) 55%

          6. Availability of tumor tissue specimen after surgery.

          7. Participants agree to undergo a core needle biopsy for genomic testing and organoid
             drug sensitivity assay.

          8. Histologically proven diagnosis of breast cancer.

          9. Patients have HER2-positive disease. HER2-positive disease was defined as follows:
             disease which overexpresses HER-2 by immunohistochemistry (IHC) 3+ and/or has HER2
             amplification according to fluorescence in situ hybridization (FISH).

         10. Had hormonal receptors (ER and PgR) assessed.

         11. Signed informed consent.

         12. Able to comply with the protocol.

        Exclusion Criteria:

          1. Metastatic disease (Stage IV) or bilateral breast cancer.

          2. Any previous systemic therapy (including chemotherapy, immunotherapy, HER2 targeted
             agents, and antitumor vaccines) for cancer, or radiation therapy for cancer.

          3. Prior breast or non-breast malignancy within 5 years prior to study entry.

          4. Inadequate bone marrow, renal, or liver function

          5. History or evidence of cardiovascular condition

          6. Severe, uncontrolled systemic disease

          7. Participants with poorly controlled diabetes or with evidence of clinically
             significant diabetic vascular complications.

          8. Pregnancy or breast-feeding women.

          9. Participants who received any investigational treatment within 4 weeks of study start.

         10. Participants with known infection with human immunodeficiency virus (HIV), hepatitis B
             virus, or hepatitis C virus.

         11. Current chronic daily treatment with corticosteroids (dose >10 mg methylprednisolone
             or equivalent [excluding inhaled steroids]).

         12. Known hypersensitivity to any of the study drugs or excipients
    Maximum Eligible Age:70 Years
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Percent Change in Standardized Uptake Value (SUV) on Positron Emission Tomography and Change in Gene Expression With Response
    Time Frame:From baseline to day 15
    Safety Issue:
    Description:Change in SUVmax from baseline to Day 15 on 18-FDG PET and 68Ga-Affibody HER-2 Imaging PET in correlation with pathological complete response (pCR) in patients treated with preoperative pertuzumab/trastuzumab.

    Secondary Outcome Measures

    Measure:Pathologic complete response in the breast and lymph nodes (ypT0/Tis ypN0)
    Time Frame:Immediately after the surgery
    Safety Issue:
    Description:To determine whether the composite markers can predict pathologic complete response in the breast and lymph nodes in HER-2 positive breast cancer with PH combination with chemotherapy adjuvant therapy. Defined as the absence of any invasive component in the resected breast specimen and all resected lymph nodes following completion of neoadjuvant therapy (ypT0/Tis ypN0).
    Measure:Invasive disease-free survival (iDFS) (excluding Second Primary Non-Breast Cancer [SPNBC])
    Time Frame:Following surgery until Year 5
    Safety Issue:
    Description:To determine the correlation between the composite markers and invasive disease free survival in HER-2 positive breast cancer patients receiving docetaxel, carboplatin, and trastuzumab plus pertuzumab pre-operatively. iDFS event was defined as the first occurrence of one of the following events: Ipsilateral invasive breast tumor recurrence; ipsilateral local-regional invasive breast cancer recurrence; distant recurrence; death attributable to any cause; contralateral invasive breast cancer. All SPNBCs and in situ carcinomas (including ductal carcinoma in situ [DCIS] and lobular carcinoma in situ [LCIS]) and non-melanoma skin cancer were excluded as an event.
    Measure:iDFS (including SPNBC)
    Time Frame:Following surgery until Year 5
    Safety Issue:
    Description:The iDFS event was defined as the first occurrence of one of the following events: Ipsilateral invasive breast tumor recurrence; ipsilateral local-regional invasive breast cancer recurrence; distant recurrence; death attributable to any cause; contralateral invasive breast cancer; SPNBC (with the exception of non-melanoma skin cancers and in situ carcinoma of any site).
    Measure:Overall survival (OS)
    Time Frame:Following surgery until Year 5
    Safety Issue:
    Description:To determine the correlation between the composite markers and overall survival in HER-2 positive breast cancer patients receiving docetaxel, carboplatin, and trastuzumab plus pertuzumab pre-operatively. Percentage of participants who died due to any cause is reported.

    Details

    Phase:N/A
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Fudan University

    Last Updated

    May 4, 2020