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Study of Poziotinib in Participants With HER2-Positive Metastatic Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02659514
Recruitment Status : Completed
First Posted : January 20, 2016
Results First Posted : February 10, 2022
Last Update Posted : March 11, 2022
Sponsor:
Information provided by (Responsible Party):
Spectrum Pharmaceuticals, Inc

Brief Summary:
The purpose of this study is to establish the dose regimen and evaluate the preliminary efficacy and the safety/tolerability of poziotinib in participants with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer who have received at least two prior HER2-directed treatment regimens.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: Poziotinib Phase 2

Detailed Description:

This is a phase 2, open-label, multicenter study to establish the dose regimen and evaluate the preliminary efficacy and the safety/tolerability of poziotinib in participants with HER2-positive metastatic breast cancer who have received at least two prior HER2-directed treatment regimens.

Each treatment cycle will be 21 days in duration. During each 21-day cycle, participants who are eligible for participation will receive poziotinib orally once daily.

All treated participants will be followed up until disease progression, death, intolerable adverse events or up to a maximum of 24 months whichever comes earlier.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 67 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Study of Poziotinib in Patients With HER2-Positive Metastatic Breast Cancer (MBC) Who Have Received Prior HER2 Regimens for MBC
Actual Study Start Date : February 22, 2016
Actual Primary Completion Date : March 11, 2020
Actual Study Completion Date : March 11, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: Cohort 1: Poziotinib 24 mg
Participants received poziotinib 24 milligrams (mg), administered as three 8 mg tablets, orally, once daily (QD) on an intermittent dosing schedule of 14 days on treatment followed by 7 days off treatment, in a 21-day cycle until disease progression, death, intolerable adverse events (AEs) or for up to a maximum of 24 months, whichever occurs first.
Drug: Poziotinib
8 mg oral tablets, administered QD.
Other Name: HM781-36B

Experimental: Cohort 2: Poziotinib 16 mg
Participants received poziotinib 16 mg, administered as two 8 mg tablets, orally, QD, on a continuous dosing schedule in a 21-day cycle until disease progression, death, intolerable AEs or for up to a maximum of 24 months, whichever occurs first.
Drug: Poziotinib
8 mg oral tablets, administered QD.
Other Name: HM781-36B




Primary Outcome Measures :
  1. Objective Response Rate (ORR) [ Time Frame: Up to 24 months ]
    ORR was defined as the percentage of participants whose best overall response (BOR) was complete response (CR) or partial response (PR) among participants in the Evaluable Population assessed per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). ORR was based on investigator assessed BOR. Per RECIST v1.1 for target lesions, CR was disappearance of all target tumor lesions (TLs) and all target lymph nodes (LNs) with short axis <10mm. PR was ≥30% decrease in sum of diameters (SOD) from Baseline, and not progressive disease (PD) (≥20% increase in SOD from previous smallest SOD on study, and an absolute increase of ≥5mm).


Secondary Outcome Measures :
  1. Progression Free Survival (PFS) [ Time Frame: Up to 24 Months ]
    PFS was the duration of time (in months) from first administration of study treatment to date of first documented disease progression or death from any cause. PFS of living participants without documented PD was censored at the time of last tumor assessment or the date of first treatment if there was no post-baseline tumor assessment. Per RECIST v1.1 for target lesions, PD was defined as ≥20% increase in SOD from previous smallest SOD on study, and an absolute increase of ≥5mm.

  2. Disease Control Rate (DCR) [ Time Frame: Up to 24 months ]
    DCR was the percentage of participants whose best response was CR, PR or stable disease (SD) among participants in the Evaluable Population assessed per RECIST v1.1. DCR was based on investigator-assessed BOR. Per RECIST v1.1 for target lesions, CR was defined as disappearance of all target TLs and all target LNs with short axis <10mm. PR was ≥30% decrease in sum of diameters (SOD) from Baseline, and not progressive disease (≥20% increase in SOD from previous smallest SOD on study, and an absolute increase of ≥5mm). SD was SOD change neither sufficient for PR nor sufficient for PD.

  3. Time to Progression (TTP) [ Time Frame: Up to 24 months ]
    TTP was defined as the time (in months) from first administration of study drug to tumor progression, which excluded death without tumor progression, by the end of study. TTP of participants who died without documented PD was censored at date of death. TTP of living participants without documented PD was censored at the same time as PFS, which was the last tumor assessment or the date of first treatment if there was no post-baseline tumor assessment. Per RECIST v1.1 for target lesions, PD was defined as ≥20% increase in SOD from previous smallest SOD on study, and an absolute increase of ≥5mm.

  4. Duration of Response (DoR) [ Time Frame: Up to 24 months ]
    DoR was evaluated only for participants whose BOR was CR or PR and was defined as the time (in months) from the date that response evaluation criteria were first met for CR or PR (whichever status was recorded first) until the first subsequent date that PD or death was documented. DoR of participants without documented PD or death was censored at the time of last tumor assessment. Per RECIST v1.1 for target lesions, CR was defined as disappearance of all target tumor lesions (TLs) and all target lymph nodes (LNs) with short axis <10mm. PR was defined as ≥30% decrease in sum of diameters (SOD) from Baseline, and not PD. PD was defined as ≥20% increase in SOD from previous smallest SOD on study, and an absolute increase of ≥5mm).

  5. Number of Participants With One or More Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: From the first dose of study drug administration until 35 (± 5) days after the last dose of study drug administration (Up to approximately 25 months) ]
    An AE was defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. TEAEs were AEs that occurred or worsened from the first dose of study treatment until 35 (± 5) days after the last dose of study treatment.

  6. Pharmacokinetic Analysis (Drug Concentration Measurements) [ Time Frame: For Cohort 1: Pre-dose and 1 and 2 hours post-dose on Day 1 of Cycles 1, 2, and 3, and pre-dose on Day 14 of Cycle 1 For Cohort 2: Day 1 of Cycle 1 pre-dose and 30 minutes, 1,1.5,2,3, 4, 6, and 24 hours post-dose of Day 1 of Cycle 1 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Histopathologically confirmed primary breast cancer with metastatic lesions.
  2. Confirmed HER2 overexpression or gene-amplified tumor
  3. At least two prior HER2-directed therapy regimens for breast cancer, including trastuzumab and trastuzumab emtansine
  4. Measurable disease per Response Evaluation Criteria for Solid Tumors version 1.1 (RECIST v1.1)
  5. Participant is at least 18, and ≤90 years of age.
  6. Adequate hematologic, hepatic, and renal function
  7. Eastern Cooperative Oncology Group (ECOG) performance status <= 2

Exclusion Criteria:

  1. Previous treatment with poziotinib prior to study participation
  2. Brain metastases that are symptomatic or require therapy to control symptoms, as well as any history of radiation, surgery, or other therapy, including steroids, to control symptoms from brain metastases within 15 days of enrollment.
  3. Anticancer chemotherapy, biologics, immunotherapy, cure-intent radiotherapy, or investigational treatment within 15 days, except for hormone therapy, palliative therapy, or supportive therapy.
  4. History of congestive heart failure Class III/IV according to the New York Heart Association (NYHA) Functional Classification or serious cardiac arrhythmias requiring treatment.
  5. Cardiac ejection fraction <50%
  6. History of other malignancies within the last 5 years
  7. Participant is pregnant or breast-feeding.
  8. Unable to take drugs orally

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): NCT02659514


Locations
Show Show 35 study locations
Sponsors and Collaborators
Spectrum Pharmaceuticals, Inc
Investigators
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Study Director: Shanta Chawla, MD Spectrum Pharmaceuticals, Inc
  Study Documents (Full-Text)

Documents provided by Spectrum Pharmaceuticals, Inc:
Study Protocol  [PDF] July 14, 2017
Statistical Analysis Plan  [PDF] January 4, 2021

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Responsible Party: Spectrum Pharmaceuticals, Inc
ClinicalTrials.gov Identifier: NCT02659514    
Other Study ID Numbers: SPI-POZ-201
First Posted: January 20, 2016    Key Record Dates
Results First Posted: February 10, 2022
Last Update Posted: March 11, 2022
Last Verified: February 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Metastatic Breast Cancer
HER2-positive
Pan-HER inhibitor
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases