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

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ClinicalTrials.gov Identifier: NCT03429101
Recruitment Status : Active, not recruiting
First Posted : February 12, 2018
Last Update Posted : February 6, 2019
Sponsor:
Information provided by (Responsible Party):
Spectrum Pharmaceuticals, Inc

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.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: Poziotinib Drug: T-DM1 Phase 1

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).


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 6 participants
Intervention Model: Single Group Assignment
Intervention Model Description:
  • Part 1: Dose Finding To determine the MTD/MAD of poziotinib in combination with the standard dose of T-DM1 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 of the study to further evaluate the safety and efficacy.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b Study of Poziotinib in Combination With T-DM1 in Women With Advanced or Metastatic HER2-Positive Breast Cancer
Actual Study Start Date : April 4, 2018
Estimated Primary Completion Date : January 15, 2021
Estimated Study Completion Date : June 15, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
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
Poziotinib is a tablet for oral administration.

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




Primary Outcome Measures :
  1. Objective Response Rate (ORR) [ Time Frame: 3 Years ]
    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.


Secondary Outcome Measures :
  1. Disease Control Rate (DCR) [ Time Frame: 27 weeks ]
    Evaluate the Disease Control Rate (DCR) at 9, 18, and 27 weeks in patients treated at the MTD/MAD.

  2. Progression-free Survival (PFS) [ Time Frame: 3 years ]
    Evaluate Progression-free Survival (PFS) in patients treated with MTD/MAD.



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Ages Eligible for Study:   18 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03429101


Locations
United States, California
Pacific Cancer Medical Center, Inc.
Anaheim, California, United States, 92801
Sponsors and Collaborators
Spectrum Pharmaceuticals, Inc

Responsible Party: Spectrum Pharmaceuticals, Inc
ClinicalTrials.gov Identifier: NCT03429101     History of Changes
Other Study ID Numbers: SPI-POZ-101
First Posted: February 12, 2018    Key Record Dates
Last Update Posted: February 6, 2019
Last Verified: February 2019

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Spectrum Pharmaceuticals, Inc:
Poziotinib
HER2 Positive
T-DM1

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Ado-trastuzumab emtansine
Trastuzumab
Maytansine
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic