PET Dynamics to Response-Adapted Neoadjuvant Therapy in TNBC

NCT ID: NCT06245889

Last Updated: 2025-09-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-05-01

Study Completion Date

2030-06-30

Brief Summary

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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).

Detailed Description

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Eligible participants will undergo baseline procedures including research bloodwork, MRI and PET scan. Participants will then be treated with one cycle of paclitaxel, carboplatin and pembrolizumab (TCarbo/pembro). At the end of Cycle one patients will undergo repeat procedures (bloodwork and PET scan), and then continue with treatment for an additional three cycles. ctDNA will be collected on day 1 of each cycle. At the end of treatment patients will undergo repeat MRI.

Patients achieving a clinical complete response (CR) on MRI will proceed with surgery. Patients with clinical residual disease (RD) on MRI will be recommended a biopsy, and be recommended "rescue" neoadjuvant doxorubicin and cyclophosphamide with pembrolizumab (AC/pembro) for four additional cycles, and then proceed with surgery. Note: patients/treating physician may opt to proceed with surgery.

Archival tissue will be collected from the surgical product. Patients achieving a pathologic CR (pCR) may proceed with adjuvant pembrolizumab per standard of care, and treating physician's discretion. Patients with pathological RD may proceed with "rescue" adjuvant AC/pembrolizumab for four additional cycles (if not given neoadjuvantly), per treating physician discretion. The participants may also receive Aadjuvant capecitabine or olaparib as indicated and per treating physician's discretion.

Conditions

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Triple Negative Breast Cancer

Study Design

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Allocation Method

NA

Intervention Model

SEQUENTIAL

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).
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Neoadjuvant therapy

4 cycles of paclitaxel/carboplatin/pembrolizumab

Group Type EXPERIMENTAL

Paclitaxel

Intervention Type DRUG

chemotherapy

Carboplatin

Intervention Type DRUG

chemotherapy

Pembrolizumab

Intervention Type DRUG

immunotherapy

Doxorubicin

Intervention Type DRUG

additional chemotherapy - neoadjuvant or adjuvant rescue

Cyclophosphamide

Intervention Type DRUG

additional chemotherapy - adjuvant rescue

Olaparib

Intervention Type DRUG

adjuvant rescue

Capecitabine

Intervention Type DRUG

adjuvant rescue

Interventions

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Paclitaxel

chemotherapy

Intervention Type DRUG

Carboplatin

chemotherapy

Intervention Type DRUG

Pembrolizumab

immunotherapy

Intervention Type DRUG

Doxorubicin

additional chemotherapy - neoadjuvant or adjuvant rescue

Intervention Type DRUG

Cyclophosphamide

additional chemotherapy - adjuvant rescue

Intervention Type DRUG

Olaparib

adjuvant rescue

Intervention Type DRUG

Capecitabine

adjuvant rescue

Intervention Type DRUG

Other Intervention Names

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Taxol Paraplatin Keytruda Adriamycin Cytoxan Lynparza Xeloda

Eligibility Criteria

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Inclusion Criteria

1. Stage II-III TNBC - estrogen receptor (ER) and progesterone receptor (PR) up to and including 10% is eligible
2. Age ≥ 18 years
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
4. Eligible for standard chemo-immunotherapy as determined by treating physician, including consideration of:

1. Adequate marrow and organ function
2. Co-morbid conditions do not preclude the use of chemo-immunotherapy (such as uncontrolled autoimmune disease, or the use of immunosuppressive medications)
5. Patients must have the ability to understand and the willingness to sign a written informed consent prior to registration on study

Exclusion Criteria

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

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

OTHER

Sponsor Role lead

Breast Cancer Research Foundation

OTHER

Sponsor Role collaborator

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Cesar A Santa-Maria, MD

Role: STUDY_CHAIR

Johns Hopkins University

Locations

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Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Site Status RECRUITING

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Cesar A Santa-Maria, MD

Role: CONTACT

410-614-0874

Hopkins Breast Trials

Role: CONTACT

410-614-1361

Facility Contacts

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Hopkins Breast Trials

Role: primary

410-614-1361

JHCCCRO

Role: primary

410-955-8866

References

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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.

Reference Type RESULT
PMID: 32101663 (View on PubMed)

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.

Reference Type RESULT
PMID: 32966830 (View on PubMed)

Other Identifiers

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IRB00398141

Identifier Type: OTHER

Identifier Source: secondary_id

J2395

Identifier Type: -

Identifier Source: org_study_id

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