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

NCT ID: NCT04281641

Last Updated: 2020-05-04

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 94 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-04-21
• Study Completion Date: 2030-04-30

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.

Conditions

HER2-positive Breast Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

TCHP

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.

Group Type: EXPERIMENTAL

TCHP

Intervention Type: DIAGNOSTIC_TEST

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.

Interventions

TCHP

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.

Intervention Type: DIAGNOSTIC_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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fudan University

OTHER

Sponsor Role: lead

Responsible Party

Jiong Wu

Professor, Department of Breast Surgery Vice President, Cancer Hospital, Fudan University

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Shanghai Cancer Center, Fudan University

Shanghai, Shanghai Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Jiong Wu, MD

Role: CONTACT

wujiong1122@vip.sina.com

+862164175590 ext. 88607

Facility Contacts

Jiong Wu, MD

Role: primary

wujiong1122@vip.sina.com

+862164175590 ext. 88607

Other Identifiers

SCHBCC-NO28

Identifier Type: -

Identifier Source: org_study_id