NCT03820063

Image-guided De-escalation of Neo-adjuvant Chemotherapy in HER2-positive Breast Cancer: the TRAIN-3 Study

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 462 (estimated)
• Sponsor: Borstkanker Onderzoek Groep · Network
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a multicenter, single arm, phase II study evaluating the efficacy of image-guided de-escalating neoadjuvant treatment with paclitaxel, Herceptin® (trastuzumab), carboplatin, and pertuzumab (PTC-Ptz) in stage II-Ill HER2-positive breast cancer.

Detailed description

High pathological complete response (pCR)-rates are seen using different neoadjuvant chemotherapy schedules with trastuzumab and pertuzumab in HER2-positive stage II - III breast cancer patients. Total pCR rates in breast and axilla have been described as high as 64%, and with an even higher rate of \>80% in patients with HER2-positive and hormone receptor (HR) negative tumors. PCR is associated with better long-term outcomes in patients with HER2-positive breast cancer. Three year progression-free survival ranges between 85-90%. Neoadjuvant treatment of HER2-positive breast cancer typically consists of six to nine cycles of treatment. Longer duration of treatment is associated with higher pCR-rates but gives more toxicity. Pathological complete responses are sometimes seen after only 10-12 days of neoadjuvant treatment. It is therefore important to investigate which patients can safely be treated with less than six cycles of chemotherapy and who requires more than six cycles for maximum activity. The radiologic response of a breast tumor after neoadjuvant therapy is predictive of the pathologic response, although the accuracy differs between breast cancer subtypes. It is hypothesized that patients with an early complete radiologic response may not benefit from additional chemotherapy and can be referred for early surgery. Patients who have not achieved pCR after early surgery despite radiologic complete response (rCR) are candidates for further adjuvant chemotherapy to complete the initially planned number of treatment cycles and maintain maximum treatment activity. Imaged guided de-escalation in which the number of treatment cycles is determined by the radiologic response could thus reduce toxicity in neoadjuvant treatment while maintaining activity. This study will evaluate the efficacy of image-guided de-escalation of neoadjuvant chemotherapy in patients with HER2-positive breast cancer. To maintain efficacy, patients who do not achieve pCR will complete a total of nine cycles taxane-containing chemotherapy followed by 14 cycles of treatment with adjuvant T-DM1. Patients who achieve early pCR will continue treatment with Herceptin® and pertuzumab to complete one full year of treatment.

Conditions

• Breast Cancer

Interventions

Type	Name	Description
DRUG	PTC-Pz	* Paclitaxel 80mg/m2 administered intravenously on day 1 and day 8 * Herceptin® 6mg/kg administered intravenously on day 1 (loading dose 8mg/kg) or Herceptin® administered subcutaneously 600mg on day 1 * Carboplatin AUC 6mg•ml/min administered intravenously on day 1 * Pertuzumab 420mg administered intravenously on day 1 (loading dose 840mg) * Treatment cycles are repeated on day 22 In case of non pCR; Adjuvant T-DM1, 3.6mg/kg Q 22 days, for 14 cycles.

Timeline

• Start date: 2019-02-27
• Primary completion: 2022-11-15
• Completion: 2032-05-01
• First posted: 2019-01-29
• Last updated: 2025-09-19

Locations

52 sites across 1 country: Netherlands