Neoadjuvant Her2-targeted Therapy and Immunotherapy With Pembrolizumab

  • STATUS
    Recruiting
  • End date
    Jul 8, 2023
  • participants needed
    174
  • sponsor
    Cedars-Sinai Medical Center
Updated on 8 September 2021
paclitaxel
cancer
breast surgery
breast cancer
growth factor
metastasis
neutrophil count
pertuzumab
epidermal growth factor receptor
HER2
EGFR
primary tumor
trastuzumab
adjuvant therapy
targeted therapy
erbb2
epidermal growth factor
invasive breast cancer
immunostimulant
her1

Summary

A phase 2 open-label, randomized, multi-center trial to evaluate the efficacy and safety of neoadjuvant trastuzumab, pertuzumab and weekly paclitaxel (THP) as compared to neoadjuvant trastuzumab, pertuzumab, pembrolizumab and weekly paclitaxel (THP-K), or neoadjuvant trastuzumab, pembrolizumab and weekly paclitaxel (TH-K) in chemo naive patients with invasive human epidermal growth factor receptor 2 (HER2) positive breast cancer whose primary tumors are > 2 cm and/or clinically lymph node positive. Treatment will be followed by standard of care breast surgery and physician's choice adjuvant therapy per standard of care.

Description

A phase 2 open-label, randomized, multi-center trial to evaluate the efficacy and safety of neoadjuvant trastuzumab, pertuzumab and weekly paclitaxel (THP) as compared to neoadjuvant trastuzumab, pertuzumab, pembrolizumab and weekly paclitaxel (THP-K), or neoadjuvant trastuzumab, pembrolizumab and weekly paclitaxel (TH-K) in chemo naive patients with invasive human epidermal growth factor receptor 2 (HER2) positive breast cancer whose primary tumors are > 2 cm and/or clinically lymph node positive.

Patients will be randomized to either Arm A: THP (trastuzumab, pertuzumab and weekly paclitaxel), Arm B: THP-K (trastuzumab, pertuzumab, pembrolizumab and weekly paclitaxel) or Arm C: TH-K (trastuzumab, pembrolizumab and weekly paclitaxel). Patients will be stratified according to hormone receptor status and lymph node status. All patients will be treated weekly every three weeks for four cycles (only paclitaxel will be administered weekly) and then undergo breast surgery. Arm A patients will be regarded as the reference group.

Details
Condition Breast Cancer, HER2 Positive Breast Cancer, Breast Cancer Diagnosis, breast carcinoma, her2/neu-positive breast cancer, her2-positive breast cancer, cancer, breast
Treatment Paclitaxel, Trastuzumab, Pembrolizumab, Pertuzumab
Clinical Study IdentifierNCT03747120
SponsorCedars-Sinai Medical Center
Last Modified on8 September 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Male/female patients with histologically confirmed invasive HER2-positive (by American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines) unilateral breast cancer
Have previously untreated non-metastaic (M0), cT2-4N0 or cT1-4N1-3 (biopsies of clinically suspicious lymph nodes to confirm nodal status is encouraged)
Multifocal/centric disease is permitted if all suspicious foci have been biopsied and are consistent with HER2-positive (by ASCO/CAP guidelines) invasive breast cancer
Be a male or female subject 18 years of age on the day of signing informed consent
Male Participants: A male participant must agree to use a contraception as detailed in Appendix C of this protocol during the treatment period and for at least 6 months after the last dose of study treatment and refrain from donating sperm during this period
Female Participants: A female participant is eligible to participate if she is not pregnant (see Appendix C), not breastfeeding, and at least one of the following conditions applies: a.) Not a woman of childbearing potential (WOCBP) as defined in Appendix C OR b.) A WOCBP who agrees to follow the contraceptive guidance in Appendix C during the treatment period and for at least 6 months after the last dose of study treatment
The participant (or legally acceptable representative if applicable) provides written informed consent for the trial
Provides adequate archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue. Note: If submitting unstained cut slides, newly cut slides should be submitted to the testing laboratory within 14 days from the date slides are cut
Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
Have adequate organ function as defined by the following parameters. Specimens must be collected within 7 days prior to the start of study treatment
Absolute neutrophil count (ANC) 1500/L
Platelets 100 000/L
Hemoglobin 9.0 g/dL or 5.6 mmol/La
Renal Creatinine (1.5 ULN OR) OR Measured or calculated(b) creatinine clearance (30 mL/min for participant with creatinine levels) (GFR can also be used in place of creatinine or CrCl) (>1.5 institutional ULN)
Hepatic Total bilirubin 1.5 ULN OR direct bilirubin ULN for participants with total bilirubin levels >1.5 ULN aspartate aminotransferase (AST, SGOT) and alanine aminotransferase (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
Cardiac Echocardiogram or MUGA (multigated radionuclide angiography) Baseline LVEF 55%

Exclusion Criteria

A WOCBP who has a positive urine pregnancy test within 72 hours prior to randomization. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Note: in the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to start receiving study medication
Has received prior therapy with an anti-PD-1 (programmed death protein 1), anti-PD-L1 (Programmed death-ligand 1), or anti PD L2 (Programmed death-ligand 2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137)
Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to randomization. Note: If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment
Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis
Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Gurin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist) are live attenuated vaccines and are not allowed
Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment
Note: Participants who have entered the follow-up phase of an investigational
study may participate as long as it has been 4 weeks after the last dose of
the previous investigational agent
\. 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
\. Has a known additional malignancy that is progressing or has required
active systemic 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 (e.g. breast carcinoma, cervical cancer in situ) that have
undergone potentially curative therapy are not excluded
\. 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
\. Has a history of (non-infectious) pneumonitis that required steroids or
has current pneumonitis
\. Has an active infection requiring systemic therapy
\. Has a known history of Human Immunodeficiency Virus (HIV)
\. Has a known active Hepatitis B (defined as Hepatitis B surface antigen
[HBsAg] reactive) or Hepatitis C virus (i.d. HCV RNA [qualitative] is
detected) infection
\. Has a known history of active TB (Bacillus Tuberculosis)
\. Has a history or current evidence of any condition, therapy, or
laboratory abnormality that might confound the results of the study, interfere
with the subject's participation for the full duration of the study, or is not
in the best interest of the subject to participate, in the opinion of the
treating investigator
\. Has known psychiatric or substance abuse disorders that would interfere
with cooperation with the requirements of the trial
\. 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
\. Has significant cardiovascular disease, such as
History of myocardial infarction, acute coronary syndrome or coronary angioplasty/stenting/bypass grafting within the last 6 months
Congestive heart failure (CHF) New York Heart Association (NYHA) Class II-IV or history of CHF NYHA class III or IV
Angina pectoris requiring anti-anginal medication, uncontrolled arrhythmias, or uncontrolled hypertension (systolic blood pressure > 180mmHg and/or diastolic blood pressure > 100mmHg)
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