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TerminatedNCT03429101Updated Jan 15, 2021

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

A Phase 1 interventional study of Poziotinib and T-DM1 in Breast Cancer, sponsored by Spectrum Pharmaceuticals, Inc. Terminated at 2 sites in United States. Open to female participants aged 18 Years to 90 Years. Per ClinicalTrials.gov, last updated 2021-01-15.

Sponsored by Spectrum Pharmaceuticals, Inc · Phase 1, Interventional, and Treatment

Why this study was terminated
Dose limiting toxicity
Phase
Phase 1
Study type
Interventional
Enrollment
6
Allocation
Not applicable
Ages
18 Years to 90 Years
Sex
Female
01

Study 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.

Read the 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).

02

Conditions studied

  • Breast Cancer

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Keywords

  • Poziotinib
  • HER2 Positive
  • T-DM1
03

Who can participate

Ages eligible
18 Years to 90 Years
Sexes eligible
Female
Accepts healthy volunteers
No

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

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.
04

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
6 participants (actual)

Study arms

  • Experimental
    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.

    Drug: Poziotinib · Drug: T-DM1

Interventions

  • DrugPoziotinib

    Poziotinib is a tablet for oral administration.

  • DrugT-DM1

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

    Also known as: ado-trastuzumab emtansine

05

What researchers measure

Primary outcomes

  1. 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.

    Time frame: 3 Years

Secondary outcomes

  1. Disease Control Rate (DCR)

    Evaluate the Disease Control Rate (DCR) at 9, 18, and 27 weeks in patients treated at the MTD/MAD.

    Time frame: 27 weeks

  2. Progression-free Survival (PFS)

    Evaluate Progression-free Survival (PFS) in patients treated with MTD/MAD.

    Time frame: 3 years

06

Study locations

2 sites
  • Pacific Cancer Medical Center, Inc.
    Anaheim, California 92801, United States
  • Los Angeles Hematology Oncology Medical Group
    Glendale, California 91204, United States
07

Registry details

Key details

Study ID
NCT03429101
Lead sponsor
Spectrum Pharmaceuticals, Inc
Responsible party
Sponsor
First posted
Feb 12, 2018
Start date
Jul 13, 2018
Primary completion
Apr 17, 2019
Completion
Apr 17, 2019
Last update
Jan 15, 2021

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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This study is terminated, as verified in Jan 2021. You cannot join it, but the record below documents what was studied.

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