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

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02659514
• Other study ID #: SPI-POZ-201
• Status: Completed
• Phase: Phase 2
• Start date: February 22, 2016
• Est. completion date: March 11, 2020

Study information

• Verified date: February 2022
• Source: Spectrum Pharmaceuticals, Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 67
• Est. completion date: March 11, 2020
• Est. primary completion date: March 11, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Poziotinib
8 mg oral tablets, administered QD.

Locations

Country	Name	City	State
United States	Pacific Cancer Medical Center, Inc.	Anaheim	California
United States	St. Vincent Frontier Cancer Center	Billings	Montana
United States	Aultman Hospital	Canton	Ohio
United States	Waverly Hematology Oncology	Cary	North Carolina
United States	Charleston Cancer Center	Charleston	South Carolina
United States	Ohio State University	Columbus	Ohio
United States	North Shore Hematology Oncology Associates	East Setauket	New York
United States	Marin Cancer Care, Inc	Greenbrae	California
United States	Hattiesburg Clinic Hematology Oncology	Hattiesburg	Mississippi
United States	Triple Army Medical Cente	Honolulu	Hawaii
United States	Oncology Consultants, P.A.	Houston	Texas
United States	SAMMC - Hem/Onc Clinic	Houston	Texas
United States	Clearview Cancer Center	Huntsville	Alabama
United States	Franciscan St. Francis Health	Indianapolis	Indiana
United States	Providence Regional Cancer System	Lacey	Washington
United States	Alliance Research Centers	Laguna Hills	California
United States	PacificShores Medical Group	Long Beach	California
United States	Texas Oncology-McAllen	McAllen	Texas
United States	AMPM Research Clinic	Miami Gardens	Florida
United States	West Virginia University	Morgantown	West Virginia
United States	Magee Womens Hospital of UPMC	Pittsburgh	Pennsylvania
United States	FL Cancer Research Institute	Plantation	Florida
United States	Valley Medical Oncology Consultants	Pleasanton	California
United States	Hudson Valley Hematology Oncology Associates	Poughkeepsie	New York
United States	Carolina Blood and Cancer Care Associates PA	Rock Hill	South Carolina
United States	Washington University	Saint Louis	Missouri
United States	The University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Medical Oncology Associates, PS	Spokane	Washington
United States	Northwest Medical Specialties, PLLC	Tacoma	Washington
United States	Scott & White Memorial Hospital	Temple	Texas
United States	Oklahoma Cancer Specialists & Research Institute, LLC	Tulsa	Oklahoma
United States	The University of Kansas Cancer Center and Medical Pavilion	Westwood	Kansas
United States	White Plain Hospital	White Plains	New York
United States	Innovative Clinical Research Institute	Whittier	California
United States	Bond Clinic, P.A.	Winter Haven	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Spectrum Pharmaceuticals, Inc

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate (ORR)	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).	Up to 24 months
Secondary	Progression Free Survival (PFS)	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.	Up to 24 Months
Secondary	Disease Control Rate (DCR)	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.	Up to 24 months
Secondary	Time to Progression (TTP)	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.	Up to 24 months
Secondary	Duration of Response (DoR)	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).	Up to 24 months
Secondary	Number of Participants With One or More Treatment-Emergent Adverse Events (TEAEs)	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.	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)
Secondary	Pharmacokinetic Analysis (Drug Concentration Measurements)		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