PET Dynamics to Response-Adapted Neoadjuvant Therapy in TNBC

Triple Negative Breast Cancer Clinical Trial

— NeoADAPT  

Official title:

A Pilot Study of Neoadjuvant Response-Adapted Chemotherapy With Pembrolizumab in Patients With Stage 2 and 3 Triple Negative Breast Cancer to Determine Early PET and Biomarker Dynamics

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06245889
• Other study ID #: J2395
• Secondary ID: IRB00398141
• Status: Recruiting
• Phase: Phase 2
• Start date: May 1, 2024
• Est. completion date: June 2030

Study information

• Verified date: May 2024
• Source: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Contact: Cesar A Santa-Maria, MD
• Phone: 410-614-0874
• Email: csantam2[@]jhmi.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: June 2030
• Est. primary completion date: June 2029
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Neoplasms
• Triple Negative Breast Cancer
• Triple Negative Breast Neoplasms

Intervention

Drug:
• Paclitaxel
chemotherapy
• Carboplatin
chemotherapy
• Pembrolizumab
immunotherapy
• Doxorubicin
additional chemotherapy - neoadjuvant or adjuvant rescue
• Cyclophosphamide
additional chemotherapy - adjuvant rescue
• Olaparib
adjuvant rescue
• Capecitabine
adjuvant rescue

Locations

Country	Name	City	State
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Country where clinical trial is conducted

United States, 

References & Publications (2)

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 wi — View Citation

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. Pembroliz — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Pathologic complete response (pCR) comparison	Compare the pathologic complete response (pCR) rates among patients who achieved clinical complete response (cCR) by breast magnetic resonance imaging (MRI) and those received "rescue" neoadjuvant AC/pembrolizumab with clinical residual disease (RD) after MRI scan.	3 years
Other	Diagnostic accuracy of percent and absolute change between baseline and C1D15 measurements	Evaluate the diagnostic accuracy of percent and absolute change (between baseline and C1D15 measurements), and C1D15 absolute measurements in fluorodeooxyglucose (FDG) / positron emission tomography (PET) standardized uptake value corrected for lean body mass (SULmax) for predicting clinical complete response (cCR) using receiver operating characteristic (ROC) curve.	3 years
Other	Clinical complete response (cCR) and pathologic complete response (pCR)	Investigate if clinical complete response (cCR) by MRI is predictive of pathologic complete response (pCR).	3 years
Other	Change in microbiome	Number of patients that experienced changes in the microbiome serially over time of residual disease.	3 years
Primary	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	Pathologic complete response (pCR)	Evaluate the pathologic complete response (pCR) rate in patients with early-stage triple negative breast cancer (TNBC) treated with neoadjuvant chemo-immunotherapy.	3 years
Secondary	Circulating tumor deoxyribonucleic acid (ctDNA) clearance	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.	3 years