Treatment for HER2-enriched early breast cancer using PAM50 testing

Phase II Trial of Anti-HER2 Treatment in HER2-enriched Early Breast Cancer Identified by PAM50 (HER2E-PAM, PAMILIA Study)

This study is testing if adding a HER2-targeted treatment can help people with early breast cancer, who are HER2-negative and haven't had treatment before, feel better and achieve remission.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 59 (estimated)
• Ages: 19 Years and up
• Sex: All
• Sponsor: Gangnam Severance Hospital (other)
• Drugs / interventions: cyclophosphamide, doxorubicin
• Locations: 1 site (Seoul)
• Trial ID: NCT04817540 on ClinicalTrials.gov

What this trial studies

This phase II trial investigates the effectiveness of HER2-targeted treatment in patients with HER2-enriched early breast cancer identified through the PAM50 molecular subtyping test. The study focuses on patients who are HER2-negative based on specific criteria and have not received prior treatment for stage II-III breast cancer. By adding HER2-targeted therapy, the trial aims to increase the rate of pathologic remission in this patient population.

Who should consider this trial

Good fit: Ideal candidates include adults over 19 years with HER2-enriched early breast cancer confirmed by PAM50 testing and no prior treatment for stage II-III breast cancer.

Not a fit: Patients with systemic metastasis or those who do not meet the HER2-negative criteria will not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve remission rates for patients with HER2-enriched early breast cancer.

How similar studies have performed: Other studies have shown promise in using targeted therapies for HER2-positive breast cancer, but this specific approach using PAM50 for HER2-negative patients is relatively novel.

Eligibility criteria

Inclusion Criteria:

1. Pathologically and cytologically documented unsectable/metastatic breast cancer that :

   A. has confirmed HER2 negative expression regardless hormone receptor status
   * definition of HER2 negative breast cancer i) HER2 IHC 1+ without ISH or ii) HER2 IHC 2+ and ISH negative (average HER2 gene copy number \<4 signals/cell in single probe ISH or HER2/CEP17 ratio \<2.0 \& average HER2 gene copy number \<4 signals cell in dual-probe ISH)
2. No prior treatment of stage II-III breast cancer

   * HR+ \& HER2- breast cancer : cT1-4N1-3
   * HR- \& HER2- breast cancer : cT1N1-3 or cT2-4N0-3
3. No systemic metastasis confirmed by pathological or radiological evaluation
4. Patients over 19 years
5. Confirmed to HER2-enriched subtype by PAM50 study
6. Available FFPE 15-20 slides for evaluating PAM50 study
7. ECOG 0-1
8. Adequate bone marrow functions i) Hemoglobin≥ 9g/dL ii) ANC ≥1,500/mm3 iii) Platelet ≥100,000/mm3
9. Adequate renal functions i) creatinine : ≤ 1.5 x UNL or ii) creatinine clearance (Ccr) ≥ 50 ml/min by Cockroft formula
10. Adequate liver functions i) Bilirubine : ≤ 1.5 x UNL ii) AST/ALT : ≤ 2.5 x UNL
11. Adequate cardiac functions

    * LVEF ≥50% (with MUGA scan or TTE)
12. Females of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to first dose of study treatment.

Exclusion Criteria:

* 1\) History of previous treatments of ipsilateral or contralateral invasive breast cancer 2) Confirmation of systemic distant metastasis of breast cancer 3) History of other malignancy within the last 5 years, except curatively treated basal cell carcinoma or squamous cell carcinoma of the skin or carcinoma in situ of the cervix, less than 2cm of thyroid cancer (papillary, follicular, medullary).

  4\) inflammatory breast cancer (cT4d) 5) bilateral breast cancer(except, multifocal or multicentric breast cancer) 6) occult breast cancer 7) History of positivity for hepatitis B surface antigen, hepatitis C virus, or human immunodeficiency virus (HIV) 8) Woman of childbearing potential who is not consenting to use highly effective methods of birth control (eg, true abstinence \[periodic abstinence (eg calendar ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception\], sterilization, or other non-hormonal forms of contraception) during treatment 9) Uncontrolled infections and other serious diseases or medical conditions 10) Uncontrolled hyeprtension or clinically active cardiovascular disease: for example, cerebrovascular accident or transient isschemic attack, unstable angina, myocaridal infarction within 6 months prior to enrolment. Have symptomatic congestive heart failure (CHF; New York Heart Association II-IV) or symptomatic or poorly controlled cardiac arrhythmia.

  11\) Have any condition (eg, psychological, geographical, or medical) that does not permit compliance with the study and follow-up procedures or suggest that the patient is, in the investigator's opinion, not an appropriate candidate for the study 12) Patients who are hypesenstivie reaction to experimental drugs (doxorubicin, cyclophosphamide, paclitaxel, docetaxel, herzuma) 13) Peripheral neuropathy CTCAE v4.03 ≥ grade 2

Where this trial is running

Seoul

• Gangnam Severance Hospital — Seoul, South Korea (RECRUITING)

Study contacts

• Study coordinator: Jun Jeong

Conditions: HER2 Enriched Subtype Breast Cancer, Herzuma, PAM50 Study