Pulsed Electromagnetic Fields (PEMFs) - A Highly Selective Breast CAncer Treatment pLatform (PASCAL)

This was a single-center, open-label, Phase Ib study utilizing a 3+3 dose-escalation design. Patients with histologically confirmed ductal carcinoma were enrolled into three sequential cohorts. Dose Level 1 (DL1) enrolled patients with metastatic disease (Grade 3, Stage III/IV, ER-/HER2+) for a single 30-minute PEMF session to assess local toxicity. Dose Level 2 (DL2) enrolled patients were planned for upfront surgical resection (Grade 1-2, ER+/PR+) to assess wound-healing safety; PEMF was administered 30 minutes pre-surgery. Dose Level 3 (DL3) enrolled patients undergoing neoadjuvant chemotherapy (Grade 3, Stage I-III) to receive PEMF 30 minutes prior to their final cycle (4th cycle) of either Anthracycline (DL3a) or Taxane (DL3b) therapy. The primary endpoints were safety and incidence of device-related adverse events. The trial ended at Dose Level 3 and demonstrates that a 30-minute PEMF application is safe and well-tolerated in breast cancer patients across metastatic, pre-surgical, and neoadjuvant chemotherapy settings. The intervention had no adverse effect on surgical wound healing or on chemotherapy administration. These findings support the closure of the Phase I safety evaluation and justify progression to a Phase II trial to evaluate the efficacy of PEMF in enhancing chemotherapeutic response.

Inclusion criteria

• Histologically confirmed breast carcinoma of any subtype (any estrogen receptor, progesterone receptor and HER2 receptor status)
• ECOG 0-1.
• Non-metastatic disease for which surgery of curative intent is planned upfront or after completion of neoadjuvant chemotherapy
• Adequate organ function including the following:

• Bone marrow:

• Absolute neutrophil (segmented and bands) count (ANC) >= 1.5 x 10^9/L
• Platelets >= 100 x 10^9/L
• Hemoglobin >= 8 x 10^9/L
• Hepatic:

• Bilirubin <= 1.5 x upper limit of normal (ULN),
• ALT or AST <= 2.5x ULN, (or <=5 X with liver metastases)
• Renal:

• Creatinine <= 1.5x ULN
• Signed informed consent from subject or legal representative.
• Able to comply with study-related procedures.

Exclusion criteria

• Pregnancy.
• Breast feeding.
• Presence of fungating breast tumor or open wound in breast planned for PEMF.
• Active bleeding disorder or bleeding site.
• Second primary malignancy that is clinically detectable at the time of consideration for study enrollment.
• Major surgery within 28 days prior to study administration.
• Non-healing wound.
• Active infection that in the opinion of the investigator would compromise the subject's ability to tolerate therapy.
• History of significant neurological or mental disorder, including seizures or dementia.
• Serious concomitant disorders that would compromise the safety of the subject or compromise the subject's ability to complete the study, at the discretion of the investigator.