Trial of Neoadjuvant THP vs TCHP for HER2-Amplified/Positive Breast Cancer

Official title

A Randomized Trial of Neoadjuvant THP vs TCHP for HER2-amplified/Positive Breast Cancer (NeoTHERa)

Overview

This is a randomized phase II study to evaluate the pathological complete response (pCR) rate with two neoadjuvant regimens (Docetaxel+Carboplatin+Herceptin/Perjeta and Docetaxel+Herceptin/Perjeta) in HER2 amplified/positive early breast cancer.

Interventions

• Drug Carboplatin
  All of the treatment being received by the study participants during the course of the study is standard of care.
• Drug Docetaxel
  All of the treatment being received by the study participants during the course of the study is standard of care.
• Drug Trastuzumab (or biosimilar)
  All of the treatment being received by the study participants during the course of the study is standard of care.
• Drug Pertuzumab (or biosimilar)
  All of the treatment being received by the study participants during the course of the study is standard of care.

Primary outcome measures

• Pathologic complete response (pCR) rate in the breast and axilla in the two treatment arms [Time frame: At time of breast surgery]

Secondary outcome measures (6)

• Residual cancer burden (RCB) [Time frame: At time of breast surgery]
• Assess the toxicity and tolerability of each regimen [Time frame: Start of study treatment (6 cycles every 21 days) until 30 days after last dose of study treatment.]
• HER2DX pathological complete response (pCR) score status [Time frame: Results of HER2DX testing are expected to be available within 3-6 weeks of submission of FFPE samples]
• Recurrence-Free Survival (RFS) [Time frame: From 3- and 5-years from diagnosis]
• Event-Free Survival (EFS) [Time frame: From 3- and 5-years from diagnosis]
• Overall Survival (OS) [Time frame: From 3- and 5-years from diagnosis]

Eligibility criteria

Inclusion criteria

• Ability of participant OR Legally Authorized Representative (LAR) to understand this study, and participant or LAR willingness to sign a written informed consent
• 18 years of age or older
• Histologically confirmed cT2-T3 N0-N2, cT1 N1-N2, or cTX N1-N2 HER2 positive breast cancer (The invasive tumor must be HER2-positive based on the current ASCO-CAP guidelines; Patients are eligible regardless of estrogen receptor (ER) or progesterone receptor (PR) expression status. However, percentage of both ER and PR positivity must be documented in the pathology report.)
• No previous ipsilateral breast surgery for the current breast cancer
• No previous chemotherapy, anti-HER2 therapy, immunotherapy, endocrine therapy, or radiotherapy for the current breast cancer
• ECOG Performance Status 0-1 documented within 28 days prior to the start of study treatment (Appendix A)
• Breast and axillary imaging (including mammogram, ultrasound and/or MRI, per standard of care) within 49 days (7 weeks) prior to treatment initiation
• Subjects with clinically and/or radiographically abnormal axillary or internal mammary lymph nodes should have pathologic confirmation of disease status with image-guided biopsy or fine needle aspiration unless deemed medically unsafe
• Co-enrollment in the PRO-HER2 (HSC #160944) observational registry protocol
• Archival breast tumor tissue has been obtained or has been requested for use, which should include either a formalin-fixed paraffin-embedded (FFPE) block, or sixteen slides (fourteen 5-micron uncharged unstained slides plus either two H\&E slides or two 5-micron charged unstained slides) - from primary breast tumor only.
• Subjects with bilateral synchronous HER2 positive breast cancer are eligible if they meet other eligibility criteria
• Neuropathy: No baseline grade 2 or above neuropathy
• Not pregnant, not breastfeeding, and at least one of the following applies: Not a woman of reproductive potential as defined by institutional standards; A woman of reproductive potential who agrees to follow contraceptive guidelines per institutional standards
• Adequate organ function, defined as follows: Hematologic (assessed ≤ 21 days of treatment initiation): Absolute neutrophil count ≥ 1,500/μL (with the exception of patients with documented Fy(a-/b-) (Duffy null) immunophenotype, in which case absolute neutrophil count ≥1,200/uL is allowed), Platelets ≥ 100,000/μL, Leukocytes ≥ 3,000/μL, Hemoglobin ≥ 9.0 g/dL or ≥ 5.6 mmol/L (must be met without erythropoietin dependency and without erythrocyte transfusion within the last two weeks); Hepatic (assessed ≤ 21 days of treatment initiation): Total bilirubin ≤ 1.5x ULN, AST(SGOT) and ALT(SPGT) ≤ 2x ULN, Serum albumin ≥ 3.0 g/dL; Cardiac (assessed ≤ 49 days of treatment initiation): Normal baseline echocardiogram or MUGA scan including LVEF ≥ 50%, per standard of care

Exclusion criteria

• Current or anticipated use of other investigational agents while participating in this study
• Clinically or radiographically detected metastatic disease
• Inflammatory breast cancer
• Prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) has the potential to interfere with the safety or efficacy assessment of the treatment regimen. Note: Patients with squamous cell or basal cell carcinoma of the skin, ductal carcinoma in situ (DCIS) of the breast, or carcinoma in situ (CIS) of the uterine cervix who have undergone definitive therapy are not excluded from participation
• History of allergic reactions attributed to carboplatin, docetaxel, trastuzumab, or pertuzumab
• History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of this study, interfere with the subject's participation for the full duration of the study, or it is not in the best interest of the subject to participate, in the opinion of the treating investigator
• Pregnancy, breastfeeding, or expecting to conceive within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment. There is a potential for congenital abnormalities and for this regimen to harm breastfeeding infants.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 8 centers

• The University of Kansas Cancer Center (KUCC) — Fairway
• The University of Kansas Cancer Center - Westwood — Kansas City
• KUCC - Indian Creek — Overland Park
• KUCC - Overland Park — Overland Park
• KUCC - Briarcliff — Westwood
• KUCC - Olathe — Westwood
• The University of Kansas Cancer Center - North — Kansas City
• KUCC - Lee's Summit — Lee's Summit

Publications

• Harris, J., M. Morrow, and L. Norton, Malignant tumors of the breast, in Cancer: principles and practice of oncology, V.J. DeVita, S. Hellman, and S. Rosenberg, Editors. 1997, Lippincott-Raven: Philadelphia. p. 1557-1602.
• Untch M, Rezai M, Loibl S, Fasching PA, Huober J, Tesch H, Bauerfeind I, Hilfrich J, Eidtmann H, Gerber B, Hanusch C, Kuhn T, du Bois A, Blohmer JU, Thomssen C, Dan Costa S, Jackisch C, Kaufmann M, Mehta K, von Minckwitz G. Neoadjuvant treatment with trastuzumab in HER2-positive breast cancer: results from the GeparQuattro study. J Clin Oncol. 2010 Apr 20;28(12):2024-31. doi: 10.1200/JCO.2009.23.8 PMID 20308670
• Broglio KR, Quintana M, Foster M, Olinger M, McGlothlin A, Berry SM, Boileau JF, Brezden-Masley C, Chia S, Dent S, Gelmon K, Paterson A, Rayson D, Berry DA. Association of Pathologic Complete Response to Neoadjuvant Therapy in HER2-Positive Breast Cancer With Long-Term Outcomes: A Meta-Analysis. JAMA Oncol. 2016 Jun 1;2(6):751-60. doi: 10.1001/jamaoncol.2015.6113. PMID 26914222
• Bear HD. Indications for neoadjuvant chemotherapy for breast cancer. Semin Oncol. 1998 Apr;25(2 Suppl 3):3-12. No abstract available. PMID 9566201
• Fisher B, Bryant J, Wolmark N, Mamounas E, Brown A, Fisher ER, Wickerham DL, Begovic M, DeCillis A, Robidoux A, Margolese RG, Cruz AB Jr, Hoehn JL, Lees AW, Dimitrov NV, Bear HD. Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. J Clin Oncol. 1998 Aug;16(8):2672-85. doi: 10.1200/JCO.1998.16.8.2672. PMID 9704717
• Kuerer HM, Newman LA, Smith TL, Ames FC, Hunt KK, Dhingra K, Theriault RL, Singh G, Binkley SM, Sneige N, Buchholz TA, Ross MI, McNeese MD, Buzdar AU, Hortobagyi GN, Singletary SE. Clinical course of breast cancer patients with complete pathologic primary tumor and axillary lymph node response to doxorubicin-based neoadjuvant chemotherapy. J Clin Oncol. 1999 Feb;17(2):460-9. doi: 10.1200/JCO.1999. PMID 10080586
• Green M, Hortobagyi GN. Neoadjuvant chemotherapy for operable breast cancer. Oncology (Williston Park). 2002 Jul;16(7):871-84, 889; discussion 889-90, 892-4, 897-8. PMID 12164555
• van der Hage JA, van de Velde CJ, Julien JP, Tubiana-Hulin M, Vandervelden C, Duchateau L. Preoperative chemotherapy in primary operable breast cancer: results from the European Organization for Research and Treatment of Cancer trial 10902. J Clin Oncol. 2001 Nov 15;19(22):4224-37. doi: 10.1200/JCO.2001.19.22.4224. PMID 11709566

Identifiers

NCT: NCT07220135 · IIT-2025-NeoTHERa

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗