Trial Title:
Trial for Treatment of High Risk BC With Two Sequences of Neoadjuvant Chemotherapy With Pembrolizumab
NCT ID:
NCT06371807
Condition:
Early Breast Cancer
Triple Negative Breast Cancer
Conditions: Official terms:
Breast Neoplasms
Triple Negative Breast Neoplasms
Paclitaxel
Cyclophosphamide
Carboplatin
Pembrolizumab
Doxorubicin
Epirubicin
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
Randomized
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Pembrolizumab injection
Description:
(KXCb - PA[E]C) vs (KPA[E]C - KXCb) Pembrolizumab (K) + paclitaxel (X) + carboplatin (Cb)
followed by pembrolizumab + doxorubicin or epirubicin (A or E) + cyclophosphamide (C)
followed by pembrolizumab in the adjuvant setting vs Pembrolizumab + doxorubicin or
epirubicin (A or E) + cyclophosphamide (C) followed by pembrolizumab (K) + paclitaxel (X)
+ carboplatin (Cb) followed by pembrolizumab in the adjuvant setting
Arm group label:
(KPA[E]C - KXCb)
Arm group label:
Arm 1: (KXCb - PA[E]C)
Other name:
Doxorubicin or Epirubicin
Other name:
Cyclophosphamide
Other name:
Paclitaxel
Other name:
Carboplatin
Summary:
Phase II, randomized, Active-controlled open label trial for treatment of high risk,
HR-/HER2- (triple negative) breast cancer, with two sequences of neoadjuvant chemotherapy
on a background of pembrolizumab
Detailed description:
This is a randomized, open-label, pilot study to evaluate the existence of a differential
tumor immunomodulatory profile of neoadjuvant pembrolizumab in combination with
paclitaxel and carboplatin vs pembrolizumab in combination with EC/AC in patients with
triple negative, tumor infiltrating lymphocytes (TILs) enriched, early breast cancer to
allow the optimization of future de-escalation strategies. There will be crossover
between treatment arms when moving from the neoadjuvant to adjuvant treatment period for
completion of standard chemotherapy plus pembrolizumab.
The chemotherapy regimen included in this study is built upon previous studies of
pembrolizumab plus chemotherapy. The synergistic effect of different chemotherapy
backbone and pembrolizumab will be studied as part of a 2-arm study:
Arm 1: (KXCb - PA[E]C): Pembrolizumab (K) every 3 weeks (Q3W) + paclitaxel (X) +
carboplatin (Cb) once weekly (QW) for 4 cycles in the neoadjuvant setting followed by
pembrolizumab + doxorubicin or epirubicin (A or E) + cyclophosphamide (C) for 4 cycles
followed by pembrolizumab every 6 weeks for 5 cycles (total of 1 year of pembrolizumab)
in the adjuvant setting.
Arm 2: (KPA[E]C - KXCb): Pembrolizumab + doxorubicin or epirubicin (A or E) +
cyclophosphamide (C) for 4 cycles in the neoadjuvant setting followed by pembrolizumab
(K) every 3 weeks (Q3W) + paclitaxel (X) + carboplatin (Cb) once weekly (QW) for 4 cycles
followed by pembrolizumab every 6 weeks for 5 cycles (total of 1 year of pembrolizumab)
in the adjuvant setting.
In case of clinical evidence of non-pCR, i.e., biopsy proven residual disease after the
neoadjuvant phase, patients can proceed to the crossover part of the adjuvant phase
before surgery (i.e., 4 cycles of chemotherapy plus pembrolizumab) receiving the
remaining administrations of pembrolizumab after surgery.
Criteria for eligibility:
Criteria:
Inclusion Criteria: Participants are eligible to be included in the study only if all the
following criteria apply:
1. Be willing and able to provide written informed consent for the trial. The subject
may also provide consent for Future Biomedical Research. However, the subject may
participate in the main trial without participating in Future Biomedical Research.
2. Be a female or male participant who is at least 18 years of age on the day of
signing informed consent.
3. Have locally histologically confirmed diagnosis of invasive carcinoma of the breast
that is classified as TNBC, as defined by the most recent ASCO/CAP guidelines.
4. Has locally confirmed tumor infiltrating lymphocytes (stromal) (sTILs) equal to or
above 10%, as defined by the most recent International Guidelines on TIL Assessment
in Breast Cancer.
5. Have previously untreated non-metastatic (M0) TNBC defined as the following combined
primary tumor (T) and regional lymph node (N) staging per current AJCC staging
criteria for breast cancer staging criteria as assessed by the investigator based on
radiological and/or clinical assessment:
1. T1c, N1-N2
2. T2, N0-N2
3. T3, N0-N2
4. T4a-d, N0-N2 Note: bilateral tumors (ie, synchronous cancers in both breasts)
and/or multi-focal (ie, 2, separate lesions in the same quadrant)/multi-centric
(ie, 2 separate lesions in different quadrants) tumors are allowed, as well as
inflammatory breast cancer, and the tumor with the most advanced T stage should
be used to assess the eligibility. If the subject has either bilateral or
multi-focal/multi-centric disease, TNBC needs to be confirmed in at least 2
lesions/breast/focus. Beyond this rule, the extent of tumor biopsy confirmation
is based on the best clinical judgment by local investigators.
6. Provide a core needle biopsy consisting of at least 3 separate tumor cores from the
primary tumor at screening to the designated central biobank (or responsible
laboratories) and is willing to provide a second biopsy at the end of the first
cycle of treatment.
Note: Detailed instructions on sample collection, processing, storage and shipment
to the central biobank are provided in the Laboratory Manual.
7. Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
performed within 10 days of treatment initiation.
8. Have left ventricular ejection fraction (LVEF) of ≥50% or ≥ institution lower limit
of normal (LLN) as assessed by echocardiogram (ECHO) or multigated acquisition
(MUGA) scan performed at screening.
9. Have adequate organ function as defined in the following table (Table 2). Specimens
must be collected within 28 days prior to the start of study intervention.
10. Male participants:
A male participant must agree to use a contraception as detailed in Appendix 3 of this
protocol during the treatment period and for at least 12 months after the last dose of
cyclophosphamide or 6 months after last chemotherapy (whichever occurs last) and refrain
from donating sperm during this period.
Female participants:
A female participant is eligible to participate if she is not pregnant (see Appendix 3),
not breastfeeding, and at least one of the following conditions applies:
a. Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR b. A WOCBP
who agrees to follow the contraceptive guidance in Appendix 3 during the treatment period
and for at least 12 months after the last dose of cyclophosphamide or 6 months after last
chemotherapy (whichever occurs last).
- Exclusion Criteria:
Participants are excluded from the study if any of the following criteria apply:
1. Has a history of invasive malignancy ≤5 years prior to signing informed consent
except for adequately treated basal cell or squamous cell skin cancer or in situ
cervical cancer.
2. Has received prior chemotherapy, targeted therapy, and radiation therapy within the
past 12 months.
3. 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).
4. Is currently participating in or has participated in an interventional clinical
trial with an investigational compound or device within 4 weeks of the first dose of
treatment in this current trial.
Note: subject should be excluded if he/she received an investigational agent with
anticancer or anti-proliferative intent within the last 12 months.
5. Has received a live vaccine or live-attenuated vaccine within 30 days prior to the
first dose of study drug. Administration of killed vaccines is allowed.
6. 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.
7. Has active autoimmune disease that has required systemic treatment in the past 2
years (i.e. with use of disease modifying agents, corticosteroids or
immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or
physiologic corticosteroid replacement therapy for adrenal or pituitary
insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
8. Has a history of (non-infectious) pneumonitis/interstitial lung disease that
required steroids or has current pneumonitis/interstitial lung disease.
9. Has significant cardiovascular disease, such as:
1. History of myocardial infarction, acute coronary syndrome or coronary
angioplasty/stenting/bypass grafting within the last 6 months
2. Congestive heart failure (CHF) New York Heart Association (NYHA) Class II-IV or
history of CHF NYHA class III or IV
10. Has a known history of Human Immunodeficiency Virus (HIV) infection.
11. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg]
reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is
detected) infection.
12. Has a known history of active TB (Bacillus Tuberculosis).
13. Has an active infection requiring systemic therapy.
14. If surgery was performed prior to screening, has persistent adverse events or
incomplete wound healing considered clinically relevant by the treating
investigator.
15. Has a history or current evidence of any condition, therapy, or laboratory
abnormality that might confound the results of the study, interfere with the
participant's participation for the full duration of the study, or is not in the
best interest of the participant to participate, in the opinion of the treating
investigator.
16. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
17. Is pregnant or breastfeeding or expecting to conceive or father children within the
projected duration of the study, starting with the screening visit through at least
12 months after the last dose of cyclophosphamide or 6 months after last
chemotherapy (whichever occurs last).
18. Has had an allogenic tissue/solid organ transplant.
19. Subjects without legal capacity who are unable to understand the nature, scope,
significance and consequences of this clinical trial and to consent
Gender:
All
Minimum age:
18 Years
Maximum age:
100 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Fundaçao Champalimaud, Avenida Brasilia,
Address:
City:
Lisbon
Zip:
1400-038
Country:
Portugal
Contact:
Last name:
Ines Sousa, MSc
Phone:
+351 210480048
Email:
ines.sousa@fundacaochampalimaud.pt
Contact backup:
Last name:
Fatima Cardoso, MD
Phone:
+351 210480048
Email:
fatimacardoso@fundacaochampalimaud.pt
Facility:
Name:
Centro Hospitalar Universitário Lisboa Norte E.P.E
Address:
City:
Lisbon
Zip:
1649-028
Country:
Portugal
Facility:
Name:
Instituto Português de Oncologia Francisco Gentil, E.P.E
Address:
City:
Oporto
Zip:
4200-072
Country:
Portugal
Contact:
Last name:
Joana Maia
Phone:
22 508 40 00
Phone ext:
2040
Email:
joana.h.maia@ipoporto.min-saude.pt
Contact backup:
Last name:
Miguel Abreu, MD
Phone:
22 508 40 00
Phone ext:
2040
Email:
antonio.m.abreu@ipoporto.min-saude.pt
Start date:
July 2024
Completion date:
December 2026
Lead sponsor:
Agency:
Fundacao Champalimaud
Agency class:
Other
Source:
Fundacao Champalimaud
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06371807
