Spots Global Cancer Trial Database for Phase1 of Neratinib+Trastuzumab, Pertuzumab, Paclitaxel in Patients With Advanced Solid Tumors/HER2+

Study Description

Brief Summary: Open label, non-randomized, dose escalation and expansion Phase Ia/b trial to evaluate the safety and tolerability of the combination of neratinib plus paclitaxel, trastuzumab and pertuzumab to determine the recommended Phase II/III dose of this combination. Neratinib will be given once daily days 1-21 and should be taken orally with food. Paclitaxel and trastuzumab will be given IV on days 1, 8, and 15 out of 21 day cycles. Pertuzumab will be given IV every 3 weeks on day 1 out of 21-day cycles. Each cycle will be 21 days in duration. Patients will continue on treatment until disease progression or intolerable toxicity.

Detailed Description: Neratinib is a potent, irreversible, small molecule panErbB inhibitor of EGFR, HER2 and HER4 tyrosine kinases. Its activity prevents the autophosphorylation of HER2 and thus halts the downstream activation of this key proliferative pathway in tumors dependent on HER2 overexpression or EGFR activation. It has shown promising clinical activity in women with HER2+ stage 2 and 3 breast cancer in the neoadjuvant setting (I-SPY 2 TRIAL) and in women with stage 4 metastatic breast cancer, although evaluation in larger phase 3 trials is required to confirm these results. The rationale for this study is to determine the feasibility of adding neratinib to a taxane based chemotherapy and the approved HER2 antagonists, trastuzumab and pertuzumab. The study will evaluate the safety and tolerability and recommended dose of daily neratinib in combination with weekly paclitaxel, trastuzumab and tri-weekly pertuzumab in patients with HER2+ advanced or metastatic disease and, if successful, determine an optimal dose to move into phase II/III testing of this combination in the neoadjuvant setting.

Keywords

Eligibility

Minimum Age: 18 Years

Eligible Ages: ADULT, OLDER_ADULT

Sex: ALL

Healthy Volunteers: No

Locations

Contact Details

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