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

Primary Purpose

HER2-positive Breast Cancer

Status
Recruiting
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
TCHP
Sponsored by
Fudan University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for HER2-positive Breast Cancer

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Shanghai Cancer Center, Fudan UniversityRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

TCHP

Arm Description

Neoadjuvant 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.

Outcomes

Primary Outcome Measures

Percent Change in Standardized Uptake Value (SUV) on Positron Emission Tomography and Change in Gene Expression With Response
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

Pathologic complete response in the breast and lymph nodes (ypT0/Tis ypN0)
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).
Invasive disease-free survival (iDFS) (excluding Second Primary Non-Breast Cancer [SPNBC])
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.
iDFS (including SPNBC)
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).
Overall survival (OS)
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.

Full Information

First Posted
February 12, 2020
Last Updated
April 30, 2020
Sponsor
Fudan University
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1. Study Identification

Unique Protocol Identification Number
NCT04281641
Brief Title
Markers to Evaluate the Efficacy of PH-based Regimen as a Neoadjuvant Therapy for Operable HER2 Positive Breast Cancer
Acronym
PHC-BC
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
Study Type
Interventional

2. Study Status

Record Verification Date
April 2020
Overall Recruitment Status
Recruiting
Study Start Date
April 21, 2020 (Actual)
Primary Completion Date
April 30, 2025 (Anticipated)
Study Completion Date
April 30, 2030 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Fudan University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HER2-positive Breast Cancer

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
94 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
TCHP
Arm Type
Experimental
Arm Description
Neoadjuvant 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.
Intervention Type
Diagnostic Test
Intervention Name(s)
TCHP
Intervention Description
Drug: Trastuzumab 8 mg/kg loading dose, then 6 mg/kg every 3 weeks, IV Other Name: Herceptin Drug: Pertuzumab 840 mg as a loading dose, then 420 mg every 3 weeks, IV Other Name: Perjeta Drug: carboplatin at target area under the plasma concentration-time curve (AUC) 6 Drug: docetaxel at a starting dose of 75 mg/m2 then to 60mg/m2 (q3w). All study drugs were administered intravenously. Procedure: 18-FDG-PET and 68 Ga-Affibody HER-2 Imaging PET will be performed at baseline, on day 15 and before surgery Genomic alterations (mutations/somatic rearrangements) are detected at baseline, on day 15 and before surgery.
Primary Outcome Measure Information:
Title
Percent Change in Standardized Uptake Value (SUV) on Positron Emission Tomography and Change in Gene Expression With Response
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.
Time Frame
From baseline to day 15
Secondary Outcome Measure Information:
Title
Pathologic complete response in the breast and lymph nodes (ypT0/Tis ypN0)
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).
Time Frame
Immediately after the surgery
Title
Invasive disease-free survival (iDFS) (excluding Second Primary Non-Breast Cancer [SPNBC])
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.
Time Frame
Following surgery until Year 5
Title
iDFS (including SPNBC)
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).
Time Frame
Following surgery until Year 5
Title
Overall survival (OS)
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.
Time Frame
Following surgery until Year 5

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Female or male, presenting for the first time with operable breast cancer, who had not received any previous treatment for an invasive malignancy. Primary tumor greater than (>) 2 cm in diameter. Age ≥ 18 years and < 70 years. Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to (</=) 1. Baseline left ventricular ejection fraction (LVEF) greater than or equal to (>/=) 55% Availability of tumor tissue specimen after surgery. Participants agree to undergo a core needle biopsy for genomic testing and organoid drug sensitivity assay. Histologically proven diagnosis of breast cancer. 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). Had hormonal receptors (ER and PgR) assessed. Signed informed consent. Able to comply with the protocol. Exclusion Criteria: Metastatic disease (Stage IV) or bilateral breast cancer. Any previous systemic therapy (including chemotherapy, immunotherapy, HER2 targeted agents, and antitumor vaccines) for cancer, or radiation therapy for cancer. Prior breast or non-breast malignancy within 5 years prior to study entry. Inadequate bone marrow, renal, or liver function History or evidence of cardiovascular condition Severe, uncontrolled systemic disease Participants with poorly controlled diabetes or with evidence of clinically significant diabetic vascular complications. Pregnancy or breast-feeding women. Participants who received any investigational treatment within 4 weeks of study start. Participants with known infection with human immunodeficiency virus (HIV), hepatitis B virus, or hepatitis C virus. Current chronic daily treatment with corticosteroids (dose >10 mg methylprednisolone or equivalent [excluding inhaled steroids]). Known hypersensitivity to any of the study drugs or excipients
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jiong Wu, MD
Phone
+862164175590
Ext
88607
Email
wujiong1122@vip.sina.com
Facility Information:
Facility Name
Shanghai Cancer Center, Fudan University
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jiong Wu, MD
Phone
+862164175590
Ext
88607
Email
wujiong1122@vip.sina.com

12. IPD Sharing Statement

Plan to Share IPD
Yes

Learn more about this trial

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

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