TAHP for Patients With HER2-positive Early Breast Cancer and Subsequent AHP Adjuvant tHerapy After Surgery

NCT03881878 | Unknown Phase 1

• 1 other identifier: 2019-01-064
• Study Type: interventional
• Target: 67
• Locations: 1 country
• Sites: 1

Brief Summary

This study was phase IB-II clinical trial that designed to evaluate the efficacy and safety of docetaxel + atezolizumab + Herceptin sc plus pertuzumab(TAHP) plus adjuvant therapy of atezolizumab + trastuzumab + pertuzumab(AHP) after surgery in female patients with HER2-positive early breast cancer. Adjuvant AHP (atezolizumab + Herceptin SC + pertuzumab) will be continued for remaining 1 year. For non-p CR patients, they are going to treat with 4 cycles of AC rather than Taxane only before AHP adjuvant therapy.

Conditions

HER2-positive Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Pathologic CR(pCR) rate of neo-adjuvant chemotherapy

  pCR rate of neoadjuvant chemotherapy with the patients with HER2+ EBC

  Pathologic Clinical response is perforemed after end of cycle 6 (each cycle is 21days).

Secondary Outcomes (1)

• Event free survival(EFS)

  3 years

Other Outcomes (1)

• Adverse events will be measured by the CTCAE scale, version 5.0

  1 year

Study Arms (2)

pathologic Complete response

EXPERIMENTAL

(A, Neoadjuvant setting): D1 X 6 cycles, q3weeks * Docetaxel (75mg/m2, IV) * Atezolizumab (1200mg, IV) * Trastuzumab (600mg, SC) * Pertuzumab (840mg loading dose at Cycle 1 followed by 420mg, IV) (B, Adjuvant setting) : D1 X 11-12 cycles, q3weeks * Atezolizumab (1200mg, IV) * Trastuzumab (600mg, SC) * Pertuzumab (420mg, IV)

Drug: TAHP and AHP

non-pathologic Complete response

EXPERIMENTAL

(A, Neoadjuvant setting): D1 X 6 cycles, q3weeks * Docetaxel (75mg/m2, IV) * Atezolizumab (1200mg, IV) * Trastuzumab (600mg, SC) * Pertuzumab (840mg loading dose at Cycle 1 followed by 420mg, IV) (B, Adjuvant setting) : * Doxorubicin(60mg/m2) plus cyclophosphamide (600mg/m2) : D1 X 4cycles q3weeks followed by * Atezolizumab (1200mg, IV), Trastuzumab (600mg, SC) and Pertuzumab (420mg, IV) D1 X 11-12 cycles q3weeks

Drug: TAHP plus AC and AHP

Interventions

TAHP and AHP DRUG

(A, Neoadjuvant setting): D1 X 6 cycles, q3weeks * Docetaxel (75mg/m2, IV) * Atezolizumab (1200mg, IV) * Tastuzumab (600mg, SC) * Pertuzumab (840mg loading dose at Cycle 1 followed by 420mg, IV) (B, Adjuvant setting) : patients with pCR:D1 X 11-12 cycles, q3weeks * Atezolizumab (1200mg, IV) * Trastuzumab (600mg, SC) * Pertuzumab (420mg, IV)

pathologic Complete response

TAHP plus AC and AHP DRUG

(A, Neoadjuvant setting): D1 X 6 cycles, q3weeks * Docetaxel (75mg/m2, IV) * Atezolizumab (1200mg, IV) * Tastuzumab (600mg, SC) * Pertuzumab (840mg loading dose at Cycle 1 followed by 420mg, IV) (B, Adjuvant setting) : patients with non-pCR * Doxorubicin(60mg/m2) plus cyclophosphamide (600mg/m2) D1 X 4cycles q3weeks followed by * Atezolizumab (1200mg, IV), Trastuzumab (600mg, SC) and Pertuzumab (420mg, IV) D1 X 11-12 cycles q3weeks

non-pathologic Complete response

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient is an adult, female ≥ 18 years old at the time of informed consent
• Patient has histologically confirmed diagnosis of breast cancer
• Patients with locally advanced breast cancer (T2-3N0-3)
• Patients with early breast cancer with high-risk (T1cN1)
• Patients with locally advanced inflammatory breast cancer
• Patient has HER2-positive breast cancer as 3+ by IHC or in-situ hybridization (ISH) amplified BC patients
• ER+ or ER-
• Agree to informed consent and willing and able to comply with the protocol
• Available pre-chemotherapy and surgery tissue (except pCR)
• For women who are not postmenopausal (≥ 12 months of non-therapy-induced amenorrhea) or surgically sterile (absence of ovaries and/or uterus): agreement to remain abstinent or use single or combined contraceptive methods that result in a failure rate of \< 1% per year during the treatment period and for at least 7 months after the last dose of study drugs. Abstinence is only acceptable if it is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.
• Examples of contraceptive methods with a failure rate of \< 1% per year include tubal ligation, male sterilization, hormonal implants, established, proper use of combined oral or injected hormonal contraceptives, and certain intrauterine devices. Alternatively, two methods (e.g., two barrier methods such as a condom and a cervical cap) may be combined to achieve a failure rate of \< 1% per year. Barrier methods must always be supplemented with the use of a spermicide.
• Patient has adequate bone marrow and organ function
• LVEF ≥55% at baseline

You may not qualify if:

• HER2-negative in surgery sample
• Tumor size less than 2cm or and N0
• Patients who have metastatic disease (M1)
• Patients who are not available tumor tissue
• Pregnant or lactating or intending to become pregnant during or within 7 months after the last dose of study treatment
• Patients who have serious underlying co-morbidities which could cause end-organ dysfunction
• Any previous treatment against including chemo, hormonal therapy
• Administration of a live, attenuated vaccine within 4 weeks before Day 1 or anticipation that such a live attenuated vaccine will be required during the study
• History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
• Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation
• Patients with prior allogeneic stem cell or solid organ transplantation
• History of autoimmune disease including, but not limited to, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Bell's palsy, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis
• History of idiopathic pulmonary fibrosis (including bronchiolitis obliterans with organizing pneumonia) or evidence of active pneumonitis on screening chest computed tomography scan
• Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis, cirrhosis, fatty liver, and inherited liver disease
• History of HIV infection, active hepatitis B (chronic or acute), or hepatitis C infection. Patients with past or resolved hepatitis B infection (defined as having a negative HBsAg test and a positive hepatitis B core antigen \[anti-HBc\] test) are eligible.

Sponsors & Collaborators

• Samsung Medical Center: lead

Study Sites (1)

Samsung Medical Center

Seoul, 135-710, South Korea

Location

Related Publications (1)

• Ahn HK, Sim SH, Suh KJ, Kim MH, Jeong JH, Kim JY, Lee DW, Ahn JH, Chae H, Lee KH, Kim JH, Lee KS, Sohn JH, Choi YL, Im SA, Jung KH, Park YH. Response Rate and Safety of a Neoadjuvant Pertuzumab, Atezolizumab, Docetaxel, and Trastuzumab Regimen for Patients With ERBB2-Positive Stage II/III Breast Cancer: The Neo-PATH Phase 2 Nonrandomized Clinical Trial. JAMA Oncol. 2022 Sep 1;8(9):1271-1277. doi: 10.1001/jamaoncol.2022.2310.

  PMID: 35797012 DERIVED

Central Study Contacts

Yeon-hee Park, MD,PhD

CONTACT

2-3410-3459; yeonh.park@samsung.com

hyunjung shin, CRC

CONTACT

2-3410-6763; hjds.shin@samsung.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Model Details: (A, Neoadjuvant setting): TAHP (Docetaxel, Atezolizumab, Trastuzumab sc and Pertuzumab) D1 X 6 cycles q3weeks, intravenous(IV) administration (B, Adjuvant setting) : patients with pCR: AHP(Atezolizumab, Trastuzumab sc and Pertuzumab) D1 X 11-12 cycles q3weeks patients with non-pCR: Doxorubicin plus cyclophosphamide: D1 X 4cycles q3weeks followed by AHP (Atezolizumab, Trastuzumab sc and Pertuzumab) D1 X 11-12 cycles q3weeks

Study Record Dates

• First Submitted: March 11, 2019
• First Posted: March 20, 2019
• Study Start: May 27, 2019
• Primary Completion: October 31, 2022
• Study Completion: October 31, 2022
• Last Updated: March 21, 2019

Record last verified: 2019-03

Locations

KR (1)