A Phase 1/2 Study Of HKI-272 (Neratinib) in Combination With Trastuzumab (Herceptin) In Subjects With Advanced Breast Cancer

Puma Biotechnology, Inc.45 enrolled

Overview

The purpose of this study is to determine the safety and efficacy of HKI-272 (neratinib) in combination with trastuzumab in patients with advanced breast cancer.

Open label phase 1/2 study of ascending multiple oral doses of HKI-272 in combination with IV trastuzumab in subjects with advanced human epidermal growth factor receptor 2 positive (HER2+) breast cancer. Three to six subjects will be enrolled in each dose group. Adverse events and dose limiting toxicities will be assessed from the first dose of study drug though day 21. When the maximum tolerated dose (MTD) of HKI-272 plus trastuzumab is determined, an additional 30 subjects will be enrolled at that dose level, and followed for progression free survival for approximately 1 year.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Advanced Breast Cancer

Interventions

HKI-272DRUG

HKI-272 by mouth

trastuzumabDRUG

trastuzumab 4 mg/kg IV as a loading dose followed by trastuzumab 2 mg/kg weekly thereafter

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Pathologic diagnosis of breast cancer with current stage IIIB, IIIC or IV not curable by available therapy * Progression following at least one Herceptin-containing cytotoxic chemotherapy regimen (neoadjuvant, adjuvant, or metastatic setting) * HER2 positive breast cancer * At least one measurable target lesion * Adequate performance status * Adequate cardiac, kidney, and liver function * Adequate blood counts * Willingness of all subjects who are not surgically sterile or post menopausal to use acceptable methods of birth control Exclusion Criteria: * More than 3 prior cytotoxic chemotherapy regimens for locally advanced or metastatic disease * Major surgery, chemotherapy, radiotherapy, investigational agents, Herceptin or other cancer therapy within 2 weeks of treatment day 1 * Prior treatment with anthracyclines with cumulative dose of \>400 mg/m\^2 * Extensive visceral disease * Active central nervous system metastases * Pregnant or breast feeding women * Significant chronic or recent acute gastrointestinal disorder with diarrhea as a major symptom * Prior exposure to HKI-272 or other HER2 targeted agents (except Herceptin and Tykerb) * Significant cardiac disease or dysfunction * History of life-threatening hypersensitivity to Herceptin * Inability or unwillingness to swallow HKI-272 capsules * Any other cancer within 5 years with the exception of contralateral breast cancer, adequately treated cervical carcinoma in situ, or adequately treated basal or squamous cell carcinoma of the skin

Locations (14)

City of Hope National Medical Center

Duarte, California, United States

LAC/USC Medical Center, USC/Norris Comprehensive Cancer Center

Los Angeles, California, United States

Outcomes

Primary Outcomes

16-week Progression-free Survival (PFS) Rate

16-week progression-free survival (PFS) rate for subjects with advanced breast cancer who receive neratinib at the maximum tolerated dose (MTD) in combination with trastuzumab, evaluable population.

Time frame: From first dose date to progression status (PD or death) at 16-week

Secondary Outcomes

Objective Response Rate (ORR)

Percentage of participants with partial response (PR) or complete response (CR) per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v.1.0: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; and Non-PD for non-target lesions, and no new lesions.

Time frame: From first dose date to progression or last tumor assessment, up to five and a half years.

Duration of Response (DOR)

Duration of response was measured from the time at which response criteria were met for complete response (CR) or partial response (PR) (whichever status was recorded first) until the first date on which recurrence or PD was objectively documented, taking as the reference for PD the smallest measurements recorded since the test article administration started.

Time frame: From start date of response to first PD, assessed up to five and half years after the first subject was randomized

Progression Free Survival (PFS)

Progression Free Survival was measured from the date of the first dose of test article until the first date on which recurrence or progression, or death due to any cause, was documented, censored at the last evaluation, investigator assessment.

Time frame: From first dose date to progression or death, assessed up to five and half years.

Clinical Benefit Rate (CBR)

The percentage of participants with a best overall response of a complete response (CR) or partial response (PR) or stable disease (SD) \>=24 weeks.

Data from ClinicalTrials.gov

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