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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Puma Biotechnology, Inc.
ClinicalTrials.gov Identifier:
NCT00398567
First received: November 9, 2006
Last updated: February 19, 2014
Last verified: February 2014
  Purpose

The purpose of this study is to learn whether it is safe and effective to administer HKI-272 (neratinib) in combination with Herceptin in patients with advanced breast cancer.


Condition Intervention Phase
Advanced Breast Cancer
Drug: HKI-272
Drug: Herceptin
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Study of HKI-272 in Combination With Trastuzumab (Herceptin) in Subjects With Advanced Breast Cancer

Resource links provided by NLM:


Further study details as provided by Puma Biotechnology, Inc.:

Primary Outcome Measures:
  • Number of participants with adverse events [ Time Frame: At screening, weekly for the first month, then at weeks 1 and 4 thereafter, and at the final visit ] [ Designated as safety issue: Yes ]
  • Objective response rate [ Time Frame: At screening and then every 2 months throughout the study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Observed maximum concentration of HKI-272 (neratinib) [ Time Frame: Prior to the first dose, on days 22 through 23 of month 1, and on day 1 in months 2 through 6 ] [ Designated as safety issue: No ]
  • Time of maximum concentration of HKI-272 (neratinib) [ Time Frame: Prior to the first dose, on days 22 through 23 of month 1, and on day 1 in months 2 through 6 ] [ Designated as safety issue: No ]
  • Area under the plasma concentration versus time curve of HKI-272 (neratinib) [ Time Frame: Prior to the first dose, on days 22 through 23 of month 1, and on day 1 in months 2 through 6 ] [ Designated as safety issue: No ]

Enrollment: 45
Study Start Date: April 2007
Estimated Study Completion Date: December 2014
Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part 1 - dose level 1
All subjects receiving HKI-272 (neratinib) in combination with trastuzumab (Herceptin)
Drug: HKI-272
neratinib 160 mg daily by mouth
Other Name: neratinib
Drug: Herceptin
Herceptin 4 mg/kg IV as a loading dose followed by Herceptin 2 mg/kg weekly thereafter
Other Name: trastuzumab
Experimental: Part 1 - dose level 2
All subjects receiving HKI-272 (neratinib) in combination with trastuzumab (Herceptin)
Drug: HKI-272
neratinib 160 mg daily by mouth
Other Name: neratinib
Drug: Herceptin
Herceptin 4 mg/kg IV as a loading dose followed by Herceptin 2 mg/kg weekly thereafter
Other Name: trastuzumab
Experimental: Part 2 - expanded MTD cohort
All subjects receiving HKI-272 (neratinib) in combination with trastuzumab (Herceptin)
Drug: HKI-272
neratinib 240 mg daily by mouth
Other Name: neratinib
Drug: Herceptin
Herceptin 4 mg/kg IV as a loading dose followed by Herceptin 2 mg/kg weekly thereafter
Other Name: trastuzumab

Detailed Description:

Open label phase 1/2 study of ascending multiple oral doses of HKI-272 in combination with IV Herceptin in subjects with advanced 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 of HKI-272 plus Herceptin is determined, an additional 30 subjects will be enrolled at that dose level, and followed for progression free survival for approximately 1 year.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00398567

Locations
United States, California
Investigational Site
Duarte, California, United States, 91010
Investigational Site
Duarte, California, United States, 91010-3000
Investigational Site
Los Angeles, California, United States, 90033
Investigational Site
Pasadena, California, United States, 91105
United States, Maryland
Investigational Site
Baltimore, Maryland, United States, 21201
United States, North Carolina
Investigational Site
Durham, North Carolina, United States, 27710
United States, Pennsylvania
Investigational Site
Philadelphia, Pennsylvania, United States, 19111
China, Jiangsu
Investigational Site
Nanjing, Jiangsu, China, 210002
China, Tianjin
Investigational Site
Tianjin, Tianjin, China, 300121
China
Investigational Site
Beijing, China, 100021
Investigational Site
Beijing, China, 100071
Investigational Site
Beijing, China, 100853
France
Investigational Site
Paris, France, 75005
Investigational Site
Saint-Herblain, France, 44805
Switzerland
Investigational Site
Lausanne, Switzerland, CH-1011
Investigational Site
Lausanne, Switzerland, 1011
Sponsors and Collaborators
Puma Biotechnology, Inc.
Investigators
Study Director: Puma Biotechnology
  More Information

No publications provided

Responsible Party: Puma Biotechnology, Inc.
ClinicalTrials.gov Identifier: NCT00398567     History of Changes
Other Study ID Numbers: 3144A1-202, B1891013
Study First Received: November 9, 2006
Last Updated: February 19, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Puma Biotechnology, Inc.:
HKI-272
neratinib
trastuzumab
Herceptin
breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Trastuzumab
Antineoplastic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014