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

NCT ID: NCT03429101

Last Updated: 2021-01-15

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-07-13
• Study Completion Date: 2019-04-17

Brief 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.

Detailed 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).

Conditions

Breast Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Poziotinib

• Part 1: Dose Finding The MTD/MAD of poziotinib in combination with the standard dose of T-DM1 will be determined by using a "3+3" design. At least 3 patients may be enrolled in each cohort before a decision is made to proceed to the next cohort.
• Part 2: MTD/MAD Expansion An additional 10 patients will be treated at the dose identified during Part 1 to further evaluate the combination at the MTD or the MAD.

Group Type: EXPERIMENTAL

Poziotinib

Intervention Type: DRUG

Poziotinib is a tablet for oral administration.

T-DM1

Intervention Type: DRUG

T-DM1 (ado-trastuzumab emtansine) is a HER2-targeted therapy for I.V. administration.

Interventions

Poziotinib

Poziotinib is a tablet for oral administration.

Intervention Type: DRUG

T-DM1

T-DM1 (ado-trastuzumab emtansine) is a HER2-targeted therapy for I.V. administration.

Intervention Type: DRUG

Other Intervention Names

ado-trastuzumab emtansine

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Spectrum Pharmaceuticals, Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Pacific Cancer Medical Center, Inc.

Anaheim, California, United States

Los Angeles Hematology Oncology Medical Group

Glendale, California, United States

Countries

United States

Other Identifiers

SPI-POZ-101

Identifier Type: -

Identifier Source: org_study_id