Neoadjuvant Pembrolizumab, Carboplatin and Paclitaxel in Triple-negative Breast Cancer

NCT06407310 | Not Yet Recruiting Phase 2

• 1 other identifier: 0617-22 TLV
• Study Type: interventional
• Target: 25
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a phase II, single-centered, open-label, single-armed study in patients with early triple-negative breast cancer that will evaluate the pathological complete response (pCR) rate of a non-anthracycline-based chemo-immunotherapy regimen. The trial includes a lead-in cycle of pembrolizumab, then a combination of paclitaxel, carboplatin, and pembrolizumab in the neoadjuvant setting.

Conditions

Triple Negative Breast Cancer

Keywords

Immunotherapy; Pembrolizumab; Breast cancer; Triple-negative breast cancer

Outcome Measures

Primary Outcomes (2)

• Pathological complete response rate (pCR= ypT0/Tis ypN0)

  The number of patients with pathological complete response (pCR) out of the total number of trial participants using a definition of ypT0/Tis ypN0 after treatment with neoadjuvant pembrolizumab, paclitaxel and carboplatin (PCb).

  3 years

• Molecular dynamics of cells in the tumor microenvironment (TME)

  The molecular state of cells in the TME will be measured at a single-cell level using single-cell RNA sequencing (scRNA-seq) before and after one dose of pembrolizumab.

  3 years

Secondary Outcomes (2)

• 3-year overall survival (OS) rate

  5 years

• 3-year event-free survival (EFS) rate

  5 years

Study Arms (1)

neoadjuvant pembrolizumab with carboplatin and paclitaxel in triple-negative breast cancer

EXPERIMENTAL

6 cycles of Pembrolizumab (Keytruda) at a dose of 200 mg given every 3 weeks for 6 cycles. The first cycle of pembrolizumab is given as a lead-in without carboplatin and paclitaxel. Carboplatin area under the curve (AUC) 1.5 and Paclitaxel 80 mg/m2, starting with the second pembrolizumab cycle, will be given weekly for 12 weeks.

Drug: Pembrolizumab; Drug: Carboplatin; Drug: Paclitaxel

Interventions

Pembrolizumab DRUG

I.V Pembrolizumab (keytruda) 200 mg every 3 weeks for 6 cycles

neoadjuvant pembrolizumab with carboplatin and paclitaxel in triple-negative breast cancer

Carboplatin DRUG

I.V Carboplatin at AUC 1.5 weekly for a total of 12 weeks.

neoadjuvant pembrolizumab with carboplatin and paclitaxel in triple-negative breast cancer

Paclitaxel DRUG

I.V Paclitaxel at 80 mg/m2 weekly for a total of 12 weeks.

neoadjuvant pembrolizumab with carboplatin and paclitaxel in triple-negative breast cancer

Eligibility Criteria

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

You may qualify if:

• Male/female participants who are at least 18 years of age on the day of signing informed consent with a histologically confirmed diagnosis of stage I or II TNBC.
• Tumor size of above 1 cm.
• The patient is willing to provide tissue from newly obtained core biopsies.
• Male participants:
• A male participant must agree to use contraception as detailed in Appendix 3 of this protocol during the treatment period and for at least 200 days after the last dose of study treatment and refrain from donating sperm during this period.
• Female participants:
• A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
• Not a woman of childbearing potential (WOCBP). OR
• A WOCBP who agrees to follow the contraceptive during the treatment period and for at least 180 days after the last dose of chemotherapy.
• The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days before the first dose of study intervention.
• Have adequate organ function as defined in the following table (Table 4). Specimens must be collected within 10 days before the start of the study intervention.
• Criteria for known Hepatitis B and C positive subjects
• Hepatitis B (HBV) and C (HCV) screening tests are not required unless:
• Known history of HBV or HCV infection

You may not qualify if:

• A WOCBP who has a positive urine pregnancy test within 72 hours prior of the first treatment dose (. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Has received prior therapy with an anti-Programmed cell death-ligand-1 (PD-L1), anti-PD-1, or anti-PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, cytotoxic T-lymphocyte associated protein 4 (CTLA-4), OX 40, CD137).
• Has received prior systemic anti-cancer therapy, including investigational agents, within 24 months of screening.
• Has received prior radiotherapy within 24 months of screening.
• Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed.
• Note: please refer to Section 5.5.2 for information on coronavirus disease 2019 (COVID-19) vaccines
• Has received an investigational agent or has used an investigational device within 4 weeks before study intervention administration.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days before the first dose of the study drug.
• Known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ, excluding carcinoma in situ of the bladder, that have undergone potentially curative therapy are not excluded.
• Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
• Has active autoimmune disease that has required systemic treatment in the past 2 years except for replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid).
• Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
• Has an active infection requiring systemic therapy.
• Has a known history of Human Immunodeficiency Virus (HIV) infection. Note: No HIV testing is required unless mandated by local health authorities.
• Concurrent active Hepatitis B (defined as HBsAg positive and/or detectable HBV DNA) and Hepatitis C virus (defined as anti-HCV Ab positive and detectable HCV RNA) infection.

Sponsors & Collaborators

• Tel Aviv Medical Center: lead

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Breast Neoplasms

Interventions

pembrolizumab; Carboplatin; Paclitaxel

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Central Study Contacts

Yasmin Leshem, MD, P.hD

CONTACT

+972-3-6972061; yasminle@tlvmc.gov.il

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: None (Open Label)
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Medical Oncologist

Model Details: Single Group Assignment

Study Record Dates

• First Submitted: March 4, 2024
• First Posted: May 9, 2024
• Study Start: July 1, 2024
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: May 9, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share