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NCT Number: NCT00398567

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

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.

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Key information

Conditions

Advanced Breast Cancer Breast Diseases Breast Neoplasms Neoplasms Neoplasms by Site Skin Diseases Skin and Connective Tissue Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Chinese Nanjing Bayi Hospital, Nanjing, Jiangsu, China

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

HKI-272

Drug

HKI-272 by mouth

Other names: neratinib

Trastuzumab

Drug

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

Other names: Herceptin

Primary outcomes

  1. 16-week Progression-free Survival (PFS) Rate

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

    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.

Secondary outcomes

  1. Objective Response Rate (ORR)

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

    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.

  2. Duration of Response (DOR)

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

    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.

  3. Progression Free Survival (PFS)

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

    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.

  4. Clinical Benefit Rate (CBR)

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

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

  5. Area Under the Curve of Neratinib Concentration

    Time frame: Prior to the first dose, and at hours 1, 2, 4, 6, 8 and 24 on days 22.

    Area Under the Curve of Neratinib concentration at day 22 following Administration of Neratinib 240 mg in combination with Trastuzumab 2 mg/kg in Subjects with Cancer.

  6. Terminal-phase Elimination Half-life of Neratinib in Combination With Trastuzumab.

    Time frame: Prior to the first dose, on days 22 through 23 of month 1, and on day 1 in months 2 through 6

    Terminal-phase elimination half-life of Neratinib at day 22 following Administration of Neratinib 240 mg in combination with Trastuzumab 2 mg/kg to Subjects with Cancer.

Sponsors and collaborators

Lead sponsor

Puma Biotechnology, Inc.

Industry

Registry information

Official study title

A Phase I/II Study of HKI-272 in Combination With Trastuzumab (Herceptin) in Subjects With Advanced Breast Cancer

Important dates

Study start
2007
Primary completion
2009
Study completion
2018
First posted
Nov 10, 2006
Registry last updated
Jul 24, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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