PET Dynamics to Response-Adapted Neoadjuvant Therapy in TNBC

NCT06245889 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: J2395IRB00398141
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

Brief Summary

Eligible patients with stage 2 and 3 triple negative breast cancer will be treated with 4 cycles of neoadjuvant paclitaxel/carboplatin/pembrolizumab. A PET scan will be performed at baseline and after 1 cycle of therapy. A breast MRI will be performed after treatment completion. Patients with complete clinical response will proceed to surgery. Patients with clinical residual disease will complete neoadjuvant rescue with 4 cycles of doxorubicin/cyclophosphamide prior to surgery. If residual disease identified after surgery, adjuvant therapy to be determined by the treating oncologist (may include doxorubicin/cyclophosphamide/pembrolizumab, capecitabine etc).

Conditions

Triple Negative Breast Cancer

Keywords

breast cancer; triple negative; neoadjuvant

Outcome Measures

Primary Outcomes (1)

• SULmax in relation to pCR

  Evaluate if lack of decrease in fluorodeooxyglucose (FDG) / positron emission tomography (PET) standardized uptake value corrected for lean body mass (SULmax) by \<40% after 1 cycle of neoadjuvant therapy correlates with residual disease at the time of surgery.

  8 months

Secondary Outcomes (2)

• Pathologic complete response (pCR)

  3 years

• Circulating tumor deoxyribonucleic acid (ctDNA) clearance

  3 years

Other Outcomes (4)

• Pathologic complete response (pCR) comparison

  3 years

• Diagnostic accuracy of percent and absolute change between baseline and C1D15 measurements

  3 years

• Clinical complete response (cCR) and pathologic complete response (pCR)

  3 years

Study Arms (1)

Neoadjuvant therapy

EXPERIMENTAL

4 cycles of paclitaxel/carboplatin/pembrolizumab

Drug: Paclitaxel; Drug: Carboplatin; Drug: Pembrolizumab; Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Olaparib; Drug: Capecitabine

Interventions

Paclitaxel DRUG

chemotherapy

Also known as: Taxol

Neoadjuvant therapy

Carboplatin DRUG

chemotherapy

Also known as: Paraplatin

Neoadjuvant therapy

Pembrolizumab DRUG

immunotherapy

Also known as: Keytruda

Neoadjuvant therapy

Doxorubicin DRUG

additional chemotherapy - neoadjuvant or adjuvant rescue

Also known as: Adriamycin

Neoadjuvant therapy

Cyclophosphamide DRUG

additional chemotherapy - adjuvant rescue

Also known as: Cytoxan

Neoadjuvant therapy

Olaparib DRUG

adjuvant rescue

Also known as: Lynparza

Neoadjuvant therapy

Capecitabine DRUG

adjuvant rescue

Also known as: Xeloda

Neoadjuvant therapy

Eligibility Criteria

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

You may qualify if:

• Stage II-III TNBC - estrogen receptor (ER) and progesterone receptor (PR) up to and including 10% is eligible
• Age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
• Eligible for standard chemo-immunotherapy as determined by treating physician, including consideration of:
• Adequate marrow and organ function
• Co-morbid conditions do not preclude the use of chemo-immunotherapy (such as uncontrolled autoimmune disease, or the use of immunosuppressive medications)
• Patients must have the ability to understand and the willingness to sign a written informed consent prior to registration on study

You may not qualify if:

• Patients unable to undergo PET or MRI
• Evidence of metastatic disease or loco-regional recurrence (i.e. distant or chest wall recurrence)
• Inflammatory breast cancer
• Previous treatment with paclitaxel, carboplatin, or immune checkpoint inhibitors

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• Breast Cancer Research Foundation: collaborator

Study Sites (2)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21287, United States

RECRUITING

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21287, United States

RECRUITING

Related Publications (2)

• Schmid P, Cortes J, Pusztai L, McArthur H, Kummel S, Bergh J, Denkert C, Park YH, Hui R, Harbeck N, Takahashi M, Foukakis T, Fasching PA, Cardoso F, Untch M, Jia L, Karantza V, Zhao J, Aktan G, Dent R, O'Shaughnessy J; KEYNOTE-522 Investigators. Pembrolizumab for Early Triple-Negative Breast Cancer. N Engl J Med. 2020 Feb 27;382(9):810-821. doi: 10.1056/NEJMoa1910549.

  PMID: 32101663 RESULT

• Mittendorf EA, Zhang H, Barrios CH, Saji S, Jung KH, Hegg R, Koehler A, Sohn J, Iwata H, Telli ML, Ferrario C, Punie K, Penault-Llorca F, Patel S, Duc AN, Liste-Hermoso M, Maiya V, Molinero L, Chui SY, Harbeck N. Neoadjuvant atezolizumab in combination with sequential nab-paclitaxel and anthracycline-based chemotherapy versus placebo and chemotherapy in patients with early-stage triple-negative breast cancer (IMpassion031): a randomised, double-blind, phase 3 trial. Lancet. 2020 Oct 10;396(10257):1090-1100. doi: 10.1016/S0140-6736(20)31953-X. Epub 2020 Sep 20.

  PMID: 32966830 RESULT

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Breast Neoplasms

Interventions

Paclitaxel; Carboplatin; pembrolizumab; Doxorubicin; Cyclophosphamide; olaparib; Capecitabine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Cesar A Santa-Maria, MD

  Johns Hopkins University

  STUDY CHAIR

Central Study Contacts

Cesar A Santa-Maria, MD

CONTACT

410-614-0874; csantam2@jhmi.edu

Hopkins Breast Trials

CONTACT

410-614-1361; HopkinsBreastTrials@jhmi.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Eligible patients with stage 2 and 3 TNBC (ER\<10% eligible) will be treated with 4 cycles of paclitaxel/carboplatin/pembrolizumab prior to surgery. A PET scan will be performed at baseline and after 1 cycle of therapy. A breast MRI will be performed after treatment completion. Patients with complete clinical response will proceed to surgery. Patients with RD will complete neoadjuvant rescue with 4 cycles of doxorubicin/cyclophosphamide prior to surgery. If residual disease identified after surgery, adjuvant therapy to be determined by the treating oncologist (may include doxorubicin/cyclophosphamide/pembrolizumab, capecitabine etc).

Study Record Dates

• First Submitted: January 23, 2024
• First Posted: February 7, 2024
• Study Start: May 1, 2024
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): June 1, 2030
• Last Updated: September 23, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)