Clinical Trials /

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

NCT03881878

Description:

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.

Related Conditions:
  • Breast Carcinoma
  • Inflammatory Breast Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: TAHP for Patients With HER2-positive Early Breast Cancer and Subsequent AHP Adjuvant tHerapy After Surgery
  • Official Title: Docetaxel Plus Atezolizumab Plus Herceptin SC and Pertuzumab (TAHP) for Patients With HER2-positive Early Breast Cancer and Subsequent Atezolizumab Plus Herceptin SC and Pertuzumab (AHP) Adjuvant tHerapy After Surgery

Clinical Trial IDs

  • ORG STUDY ID: 2019-01-064
  • NCT ID: NCT03881878

Conditions

  • HER2-positive Breast Cancer

Interventions

DrugSynonymsArms
TAHP and AHPpathologic Complete response
TAHP plus AC and AHPnon-pathologic Complete response

Purpose

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.

Detailed Description

      A, Neoadjuvant setting); 6 cycles q3weeks, intravenous(IV) administration

        -  Docetaxel (75mg/m2, intravenous(IV)) Day(D)1

        -  Atezolizumab (1200mg, IV) D1

        -  Herceptin sc (600mg subcutaneous(SC))D1

        -  Pertuzumab (840mg loading dose at Cycle 1 followed by 420mg(IV))D1

      B, Adjuvant setting : 11-12 cycles q3weeks [patients with pCR]

        -  Atezolizumab (1200mg, IV)

        -  Trastuzumab (600mg, SC)

        -  Pertuzumab (420mg, IV) D1

      [patients with non-pCR]

        -  Doxorubicin(60mg/m2), cyclophosphamide (600mg/m2) D1 X 4cycles 3weeks

        -  Atezolizumab (1200mg, IV)

        -  Trastuzumab (600mg, SC)

        -  Pertuzumab (420mg, IV) D1 X 11-12 cycles q3weeks
    

Trial Arms

NameTypeDescriptionInterventions
pathologic Complete responseExperimental(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)
  • TAHP and AHP
non-pathologic Complete responseExperimental(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
  • TAHP plus AC and AHP

Eligibility Criteria

        Inclusion Criteria:

          1. Patient is an adult, female ≥ 18 years old at the time of informed consent

          2. Patient has histologically confirmed diagnosis of breast cancer

          3. Patients with locally advanced breast cancer (T2-3N0-3)

          4. Patients with early breast cancer with high-risk (T1cN1)

          5. Patients with locally advanced inflammatory breast cancer

          6. Patient has HER2-positive breast cancer as 3+ by IHC or in-situ hybridization (ISH)
             amplified BC patients

          7. ER+ or ER-

          8. Agree to informed consent and willing and able to comply with the protocol

          9. Available pre-chemotherapy and surgery tissue (except pCR)

         10. 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.

         11. Patient has adequate bone marrow and organ function

         12. LVEF ≥55% at baseline

        Exclusion Criteria:

          1. HER2-negative in surgery sample

          2. Tumor size less than 2cm or and N0

          3. Patients who have metastatic disease (M1)

          4. Patients who are not available tumor tissue

          5. Pregnant or lactating or intending to become pregnant during or within 7 months after
             the last dose of study treatment

          6. Patients who have serious underlying co-morbidities which could cause end-organ
             dysfunction

          7. Any previous treatment against including chemo, hormonal therapy

          8. 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

          9. History of severe allergic, anaphylactic, or other hypersensitivity reactions to
             chimeric or humanized antibodies or fusion proteins

         10. Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster
             ovary cells or any component of the atezolizumab formulation

         11. Patients with prior allogeneic stem cell or solid organ transplantation

         12. 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

         13. History of idiopathic pulmonary fibrosis (including bronchiolitis obliterans with
             organizing pneumonia) or evidence of active pneumonitis on screening chest computed
             tomography scan

         14. Known clinically significant liver disease, including active viral, alcoholic, or
             other hepatitis, cirrhosis, fatty liver, and inherited liver disease

         15. 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.

         16. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase
             chain reaction assay (PCR) is negative for HCV RNA

         17. Active tuberculosis

         18. Severe infections within 4 weeks prior to Day 1, including, but not limited to,
             hospitalization for complications of infection, bacteremia, or severe pneumonia. Signs
             or symptoms of significant infection within 2 weeks prior to Day 1

         19. Received oral or IV antibiotics within 2 weeks prior to Cycle 1 Day 1

         20. Previous or concomitant malignancy of any other type that could affect compliance with
             the protocol or interpretation of results. Patients with curatively treated basal cell
             carcinoma of the skin or in situ cervix cancer are generally eligible

         21. Congestive heart failure or abnormal LVEF(LVEF is not ≥55% at baseline)

         22. Total bili >1.5 ULN (except for Gilbert's syndrome), AST/ALT > 1.5 ULN, ALP > 2.5 ULN
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Pathologic CR(pCR) rate of neo-adjuvant chemotherapy
Time Frame:Pathologic Clinical response is perforemed after end of cycle 6 (each cycle is 21days).
Safety Issue:
Description:pCR rate of neoadjuvant chemotherapy with the patients with HER2+ EBC

Secondary Outcome Measures

Measure:Event free survival(EFS)
Time Frame:3 years
Safety Issue:
Description:Event free survival of the patient with pCR vs. non-pCR

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Samsung Medical Center

Last Updated