To hear about similar clinical trials, please enter your email below
Trial Title:
Open-label, Single Center, Single-arm, Phase 2 Study of Neoadjuvant Pembrolizumab in Combination With Carboplatin and Paclitaxel in Patients With Stage 1 cT1b-T1cN0M0 Triple Negative Breast Cancer
NCT ID:
NCT06318897
Condition:
Stage 1 cT1b-T1cN0M0
Triple Negative Breast Cancer
Conditions: Official terms:
Breast Neoplasms
Triple Negative Breast Neoplasms
Paclitaxel
Albumin-Bound Paclitaxel
Cyclophosphamide
Carboplatin
Pembrolizumab
Doxorubicin
Liposomal doxorubicin
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Carboplatin
Description:
Given by IV
Arm group label:
Non-Pathologic Complete Response
Arm group label:
Pathologic Complete Response
Other name:
Paraplatin®
Intervention type:
Drug
Intervention name:
Paclitaxel
Description:
Given by IV
Arm group label:
Non-Pathologic Complete Response
Arm group label:
Pathologic Complete Response
Other name:
PACLITAXEL PROTEIN BOUND
Intervention type:
Drug
Intervention name:
Pembrolizumab
Description:
Given by IV
Arm group label:
Non-Pathologic Complete Response
Arm group label:
Pathologic Complete Response
Other name:
KEYTRUDA®
Intervention type:
Drug
Intervention name:
Doxorubicin
Description:
Given by IV
Arm group label:
Non-Pathologic Complete Response
Other name:
Doxorubicin Hydrochloride
Other name:
Adriamycin PFS®
Other name:
Adriamycin RDF™
Other name:
Adriamycin®
Other name:
Rubex®
Intervention type:
Drug
Intervention name:
Cyclophosphamide
Description:
Given by IV
Arm group label:
Non-Pathologic Complete Response
Other name:
Cytoxan®
Other name:
Neosar®
Summary:
To look at the effectiveness of the combination of pembrolizumab, carboplatin, and
paclitaxel in participants with stage 1 cT1b-T1cN0M0 Triple Negative Breast Cancer.
Detailed description:
Primary Objective To estimate the rate of pCR in patients with cT1b and T1cN0M0 TNBC
after neoadjuvant therapy with 4 cycles of Pembrolizumab + Carboplatin + Paclitaxel.
Secondary Objective To assess the safety and toxicity profile of pembrolizumab plus
chemotherapy in participants receiving an anthracycline-de-escalated regimen of
carboplatin, paclitaxel and pembrolizumab by recording the incidence of treatment
emergent adverse events.
Exploratory Objectives
1. To estimate the invasive disease-free survival (iDFS), and overall survival (OS) in
participants with cT1b-T1cN0 TNBC that receive neoadjuvant pembrolizumab plus
chemotherapy in the setting of an anthracycline de-escalation study.
2. To explore if there is a molecular signature associated with response or lack of
response to therapy.
3. To evaluate patient reported outcomes of participants receiving this de-escalated
regimen.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
Participants are eligible to be included in the study only if all of the following
criteria apply:
1. Participants must have histologically confirmed ER negative, PR negative and
HER2-negative (TNBC) defined as ER<10%, PR<10%, and HER2 negative (per 2018 ASCO CAP
guidelines). All pathology will be confirmed at the MD Anderson Houston Campus.
Participants with tumors designated as HER2 equivocal (per ASCO CAP guidelines) are
eligible if in view of treating physician patient is not considered a candidate for
HER2-targeted therapy. Participants with weakly ER or PR positive disease, defined
as ER and/or PR between 1-9% by immunohistochemistry, are eligible if the treating
physician considers the participants not eligible for adjuvant endocrine therapy.
2. AJCC 8 anatomic tumor Stage 1 T1b-T1c, N0, M0. All participants with clinically
suspicious nodes must undergo core or fine needle biopsy per standard clinical
practice to pathologically assess at least 1 suspicious index node. Participants
with suspicious nodes that are biopsy negative will be eligible.
3. Male/female participants who are at least 18 years of age on the day of signing
informed consent with histologically confirmed diagnosis of Stage 1 T1b-T1cN0M0 TNBC
will be enrolled in this study.
4. Male participants: A male participant must agree to use a contraception as detailed
in Appendix 2 of this protocol during the treatment period and for at least 120
days, corresponding to time needed to eliminate any study treatment(s) (e.g. 5
terminal half-lives for pembrolizumab and/or any active comparator/combination) plus
an additional 90 days (a spermatogenesis cycle) for study treatments with evidence
of genotoxicity at any dose after the last dose of study treatment and refrain from
donating sperm during this period.
5. Female participants: A female participant is eligible to participate if she is not
pregnant (see Appendix 2), not breastfeeding, and at least one of the following
conditions applies:
1. Not a woman of childbearing potential (WOCBP) as defined in Appendix 2 OR
2. A WOCBP who agrees to follow the contraceptive guidance in Appendix 2 during
the treatment period and for at least 120 days (corresponding to time needed to
eliminate any study treatment(s) (pembrolizumab and/or any active
comparator/combination) plus 30 days (a menstruation cycle) for study
treatments with risk of genotoxicity after the last dose of study treatment.
6. Participants who have AEs due to previous anticancer therapies must have recovered
to ≤Grade 1 or baseline. Participants with endocrine-related AEs who are adequately
treated with hormone replacement or participants who have ≤Grade 2 neuropathy are
eligible.
7. The participant provides written informed consent for the trial.
8. Archival tumor tissue sample or newly obtained [core, incisional or excisional]
biopsy of a tumor lesion not previously irradiated has been provided.
Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides.
Newly obtained biopsies are preferred to archived tissue.
9. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
(appendix 3). Evaluation of ECOG is to be performed within 7 days prior to the first
dose of study intervention.
10. Have adequate organ function as defined in the following table (Table 3). Specimens
must be collected within 10 days prior to the start of study intervention.
11. Non-English speaking participant can enroll in the study as long as they speak a
language for which interpretation can be provided by a licensed interpreter either
in person or virtually.
12. Criteria for known HIV positive participants.
1. Participants with HIV are eligible if they have well-controlled HIV with
negative viral load on ART and must not have had any AIDS-defining
opportunistic infections within the past 12 months from initiation of C1D1
study treatment.
2. HIV screening tests are not required unless:
i. Known history of HIV ii. As mandated by local health authority
13. Criteria for known Hepatitis B and C positive participants Hepatitis B and C
screening tests are not required unless:
- Known history of HBV or HCV infection
- As mandated by local health authority 13.1 Hepatitis B positive Participants
- Participants who are HBsAg positive are eligible if they have received HBV
antiviral therapy for at least 4 weeks and have undetectable HBV viral load
prior to randomization.
- Participants should remain on anti-viral therapy throughout study intervention
and follow local guidelines for HBV anti-viral therapy post completion of study
intervention. 13.2 Participants with history of HCV infection are eligible if
HCV viral load is undetectable at screening.
- Participants must have completed curative anti-viral therapy at least 4 weeks
prior to randomization.
Table 3 Adequate Organ Function Laboratory Values System Laboratory Value Hematological
Absolute neutrophil count (ANC) = ≥1500/µL Platelets = ≥100 000/µL Hemoglobin = ≥9.0 g/dL
or ≥5.6 mmol/La Renal Creatinine OR Measured or calculatedb creatinine clearance (GFR can
also be used in place of creatinine or CrCl) = ≤1.5 × ULN OR ≥30 mL/min for participant
with creatinine levels >1.5 × institutional ULN Hepatic Total bilirubin = ≤1.5 ×ULN OR
direct bilirubin ≤ULN for participants with total bilirubin levels >1.5 × ULN AST (SGOT)
and ALT (SGPT) = ≤2.5 × ULN (≤5 × ULN for participants with liver metastases) Coagulation
International normalized ratio (INR) OR prothrombin time (PT) Activated partial
thromboplastin time (aPTT) = ≤1.5 × ULN unless participant is receiving anticoagulant
therapy as long as PT or aPTT is within therapeutic range of intended use of
anticoagulants ALT (SGPT)=alanine aminotransferase (serum glutamic pyruvic transaminase);
AST (SGOT)=aspartate aminotransferase (serum glutamic oxaloacetic transaminase);
GFR=glomerular filtration rate; ULN=upper limit of normal. a Criteria must be met without
erythropoietin dependency and without packed red blood cell (pRBC) transfusion within
last 2 weeks. b Creatinine clearance (CrCl) should be calculated per institutional
standard. Note: This table includes eligibility-defining laboratory value requirements
for treatment; laboratory value requirements should be adapted according to local
regulations and guidelines for the administration of specific chemotherapies.
Exclusion Criteria:
Participants are excluded from the study if any of the following criteria apply:
1. Stage 2, 3 or 4 Triple negative breast cancer
2. Hormone Receptor positive and/or Human Epidermal Growth factor 2 (HER 2) positive
breast cancer
3. A WOCBP who has a positive urine pregnancy test within 72 hours prior to dose of
study drug (see Appendix 2). If the urine test is positive or cannot be confirmed as
negative, a serum pregnancy test will be required.
4. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or
with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg,
CTLA-4, OX-40, CD137).
5. Has received prior systemic anti-cancer therapy including investigational agents
within 4 weeks to allocation of therapy.
6. Has received prior radiotherapy within 2 weeks of start of study intervention or
radiation-related toxicities requiring corticosteroids. Note: Two weeks or fewer of
palliative radiotherapy for non-CNS disease, with a 1-week washout, is permitted.
7. 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.
8. Has received an investigational agent or has used an investigational device within 4
weeks prior to study intervention administration.
9. 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 prior to the first dose of study drug.
10. 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.
11. Has known active CNS metastases and/or carcinomatous meningitis.
12. Has severe hypersensitivity (≥Grade 3) to any of the components or any of its
excipients used in the study treatments.
13. Has active autoimmune disease that has required systemic treatment in the past 2
years except replacement therapy (eg., thyroxine, insulin, or physiologic
corticosteroid)
14. Has a history of (non-infectious) pneumonitis/interstitial lung disease that
required steroids or has current pneumonitis/interstitial lung disease.
15. Has an active infection requiring systemic therapy for >14 days from initiation of
C1D1 study treatment.
16. 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. Note: Hepatitis B and C screening tests are not required unless:
- Known history of HBV and HCV infection
- As mandated by local health authority
17. Has not adequately recovered from major surgery or has ongoing surgical
complications.
18. Has a history or current evidence of any condition, therapy, or laboratory
abnormality or other circumstance that might confound the results of the study,
interfere with the participant's participation for the full duration of the study,
such that it is not in the best interest of the participant to participate, in the
opinion of the treating investigator.
19. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
20. Is pregnant or breastfeeding or expecting to conceive or father children within the
projected duration of the study, starting with the screening visit through 120 days
after the last dose of trial treatment.
21. Has had an allogenic tissue/solid organ transplant.
22. Participants with the following contraindications to doxorubicin therapy: recent
myocardial infarction; severe myocardial insufficiency; severe arrhythmias; previous
treatment with complete cumulative doses of doxorubicin, daunorubicin, idarubicin,
and/or other anthracyclines and anthracenedione.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
MD Anderson Cancer Center
Address:
City:
Houston
Zip:
77030
Country:
United States
Status:
Recruiting
Contact:
Last name:
Oluchi Oke, MD
Phone:
832-729-8362
Email:
oukaegbu@mdanderson.org
Investigator:
Last name:
Oluchi Oke, MD
Email:
Principal Investigator
Start date:
May 29, 2024
Completion date:
September 30, 2027
Lead sponsor:
Agency:
M.D. Anderson Cancer Center
Agency class:
Other
Source:
M.D. Anderson Cancer Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06318897
http://www.mdanderson.org