Clinical Trials /

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

NCT03429101

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of Poziotinib in Combination With T-DM1 in HER2-Positive Breast Cancer
  • 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 IDs

  • ORG STUDY ID: SPI-POZ-101
  • NCT ID: NCT03429101

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
PoziotinibPoziotinib
T-DM1ado-trastuzumab emtansinePoziotinib

Purpose

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 further
      assess the MAD 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 and then for
      survival.
    

Trial Arms

NameTypeDescriptionInterventions
PoziotinibExperimentalPart 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.
  • Poziotinib
  • T-DM1

Eligibility Criteria

        Inclusion Criteria:

          -  Patient must have confirmed HER2 overexpression or gene-amplified tumor

          -  Patients must have had at least 2 lines of anti-HER2 directed therapies 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 with a history of other malignancies within the last 5 years, except for
             nonmelanoma skin cancer or carcinoma in situ of the cervix.

          -  Patient with known hypersensitivity to receptor tyrosine kinase inhibitors or any of
             the components of poziotinib tablets or T-DM1 IV solution.

          -  Patient is pregnant or breast-feeding.
      
Maximum Eligible Age:90 Years
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD)
Time Frame:2 Years
Safety Issue:
Description:The MTD or MAD of daily poziotinib in combination with T-DM1 (every 3 weeks) in women with advanced or metastatic HER2 positive breast cancer.

Secondary Outcome Measures

Measure:Disease Control Rate (DCR)
Time Frame:7 months
Safety Issue:
Description:The Disease Control Rate (DCR) at 9, 18, and 27 weeks (DCR-9, -18 and -27) is defined as the proportion of patients who have achieved CR, PR, or stable disease by RECIST 1.1 recorded at 9, 18 and 27 weeks, respectively.
Measure:Progression-free Survival (PFS)
Time Frame:2 years
Safety Issue:
Description:Progression-free Survival (PFS) is defined as the number of days from the treatment start date to the date of documented disease progression or death due to any cause. Disease progression will be determined by RECIST Version 1.1.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Spectrum Pharmaceuticals, Inc

Trial Keywords

  • Poziotinib
  • HER2 Positive
  • T-DM1

Last Updated

April 30, 2018