A Study of Poziotinib in Combination With T-DM1 in HER2-Positive Breast Cancer

Breast Cancer Clinical Trial

Official title:

A Phase 1b Study of Poziotinib in Combination With T-DM1 in Women With Advanced or Metastatic HER2-Positive Breast Cancer

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03429101
• Other study ID #: SPI-POZ-101
• Status: Terminated
• Phase: Phase 1
• Start date: July 13, 2018
• Est. completion date: April 17, 2019

Study information

• Verified date: January 2021
• Source: Spectrum Pharmaceuticals, Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a Phase 1b, open-label, multicenter study to determine the Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of poziotinib when administered with standard dosing of T-DM1 (3.6 mg/kg IV on Day 1 of each 21-day cycle) in women with advanced or metastatic HER2+ breast cancer. The poziotinib dose identified in Part 1 of the study will be used in combination with standard dose of T-DM1 in Part 2 of the study to confirm the poziotinib dose and evaluate the preliminary efficacy of the combination therapy.

Description:

In Part 1, the dose of poziotinib, in combination with the standard dose of T-DM1 (3.6 mg/kg IV) on Day 1 of each cycle will be determined using a "3+3" design with up to 3 dose levels tested beginning with 8 mg/day.

Poziotinib dose escalation/de-escalation for the next dose cohort will proceed based on the occurrence of dose-limiting toxicities (DLTs) during Cycle 1 of the dose cohort. Patients in the dose cohort, if not discontinued, will continue treatment until discontinuation.

In Part 2 of the study, approximately 10 patients will be treated at the MTD/MAD to confirm dose for safety of the combination and to evaluate preliminary efficacy. Treatment for all patients will continue until disease progression, unacceptable toxicity, or continuation of study treatment is not in the best interest of the patient.

The Screening period (Day -30 to Day -1) will last up to 30 days prior to Cycle 1, Day 1.

During each 21-day cycle, eligible patients will receive poziotinib at the assigned dose, orally, once daily. T-DM1 3.6 mg/kg IV will be administered on Day 1 of each treatment cycle.

All treated patients will be followed for response until disease progression or the start of new treatment and then for survival (3 year study duration).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 6
• Est. completion date: April 17, 2019
• Est. primary completion date: April 17, 2019
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 90 Years

Eligibility

Inclusion Criteria:

• Patient must be female, at least 18 years of age, but not older than 90 years, with advanced or metastatic HER2+ breast cancer and a life expectancy of more than 6 months

• Patient must have confirmed HER2 overexpression or gene-amplified tumor via immunohistochemistry [IHC] with IHC 3+ or IHC 2+ with confirmatory fluorescence in situ hybridization [FISH]+ or [ISH]+

• Patients must have had at least 1 line of anti-HER2 directed therapy either in the metastatic or early-stage disease setting

• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

Exclusion Criteria:

• Patient has had previous treatment with poziotinib.

• Patient has received anticancer chemotherapy, TKIs, biologics, immunotherapy, radiotherapy, or investigational treatment within 15 days. (There is no washout for hormonal therapy for breast cancer).

• Patient has a life expectancy less than 3 years due to other malignancies.

• Patient is pregnant or breast-feeding.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Poziotinib
Poziotinib is a tablet for oral administration.
• T-DM1
T-DM1 (ado-trastuzumab emtansine) is a HER2-targeted therapy for I.V. administration.

Locations

Country	Name	City	State
United States	Pacific Cancer Medical Center, Inc.	Anaheim	California
United States	Los Angeles Hematology Oncology Medical Group	Glendale	California

Sponsors (1)

Lead Sponsor	Collaborator
Spectrum Pharmaceuticals, Inc

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate (ORR)	Evaluate the Objective Response Rate (ORR) in patients treated with daily poziotinib in combination with T-DM1 (every 3 weeks) in women with advanced or metastatic HER2 positive breast cancer.	3 Years
Secondary	Disease Control Rate (DCR)	Evaluate the Disease Control Rate (DCR) at 9, 18, and 27 weeks in patients treated at the MTD/MAD.	27 weeks
Secondary	Progression-free Survival (PFS)	Evaluate Progression-free Survival (PFS) in patients treated with MTD/MAD.	3 years