PET Dynamics to Response-Adapted Neoadjuvant Therapy in TNBC

Phase 2

Recruiting

• Conditions: Triple Negative Breast Cancer
• Interventions: Drug: Paclitaxel; Drug: Carboplatin; Drug: Pembrolizumab; Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Olaparib; Drug: Capecitabine

• Registration Number: NCT06245889
• Lead Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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).

Detailed Description

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.

Study Timeline

• Study First Submitted: 2024-01-23
• Study First Submitted QC: 2024-02-05
• Study First Posted: 2024-02-07
• Status Verified: 2024-05
• Study Start: 2024-05-01
• Last Update Submitted: 2024-05-06
• Last Update Posted: 2024-05-08
• Primary Completion: 2029-06
• Study Completion: 2030-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 30

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Neoadjuvant therapy	Paclitaxel	4 cycles of paclitaxel/carboplatin/pembrolizumab
Neoadjuvant therapy	Carboplatin	4 cycles of paclitaxel/carboplatin/pembrolizumab
Neoadjuvant therapy	Pembrolizumab	4 cycles of paclitaxel/carboplatin/pembrolizumab
Neoadjuvant therapy	Doxorubicin	4 cycles of paclitaxel/carboplatin/pembrolizumab
Neoadjuvant therapy	Olaparib	4 cycles of paclitaxel/carboplatin/pembrolizumab
Neoadjuvant therapy	Cyclophosphamide	4 cycles of paclitaxel/carboplatin/pembrolizumab
Neoadjuvant therapy	Capecitabine	4 cycles of paclitaxel/carboplatin/pembrolizumab

Primary Outcome Measures

Name	Time	Method
SULmax in relation to pCR	8 months	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.

Secondary Outcome Measures

Name	Time	Method
Pathologic complete response (pCR)	3 years	Evaluate the pathologic complete response (pCR) rate in patients with early-stage triple negative breast cancer (TNBC) treated with neoadjuvant chemo-immunotherapy.
Circulating tumor deoxyribonucleic acid (ctDNA) clearance	3 years	Evaluate how circulating tumor deoxyribonucleic acid (ctDNA) kinetics collected at pre-treatment, and during and after completion of neoadjuvant treatment correlate with pathologic complete response (pCR) at the time of surgery.

Trial Locations

Locations (1)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; 🇺🇸 Baltimore, Maryland, United States