A Phase 1/2 Study Of HKI-272 (Neratinib) in Combination With Trastuzumab (Herceptin) In Subjects With Advanced Breast Cancer
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ClinicalTrials.gov Identifier: NCT00398567 |
Recruitment Status :
Completed
First Posted : November 10, 2006
Results First Posted : April 13, 2018
Last Update Posted : July 24, 2018
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Advanced Breast Cancer | Drug: HKI-272 Drug: trastuzumab | Phase 1 Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 45 participants |
Allocation: | Non-Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (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 |
Actual Study Start Date : | April 4, 2007 |
Actual Primary Completion Date : | July 31, 2009 |
Actual Study Completion Date : | March 2, 2018 |

Arm | Intervention/treatment |
---|---|
Experimental: Part 1 - dose level 1 (160 mg)
All subjects receiving HKI-272 dose level 1 in combination with trastuzumab
|
Drug: HKI-272
HKI-272 by mouth
Other Name: neratinib Drug: trastuzumab trastuzumab 4 mg/kg IV as a loading dose followed by trastuzumab 2 mg/kg weekly thereafter
Other Name: Herceptin |
Experimental: Part 1 - dose level 2 (240 mg)
All subjects receiving HKI-272 dose level 2 in combination with trastuzumab
|
Drug: HKI-272
HKI-272 by mouth
Other Name: neratinib Drug: trastuzumab trastuzumab 4 mg/kg IV as a loading dose followed by trastuzumab 2 mg/kg weekly thereafter
Other Name: Herceptin |
Experimental: Part 2 - expanded MTD cohort
All subjects receiving HKI-272 in combination with trastuzumab
|
Drug: HKI-272
HKI-272 by mouth
Other Name: neratinib Drug: trastuzumab trastuzumab 4 mg/kg IV as a loading dose followed by trastuzumab 2 mg/kg weekly thereafter
Other Name: Herceptin |
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.

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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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

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): NCT00398567
United States, California | |
City of Hope National Medical Center | |
Duarte, California, United States, 91010-3000 | |
LAC/USC Medical Center, USC/Norris Comprehensive Cancer Center | |
Los Angeles, California, United States, 90033 | |
City of Hope National Medical Center | |
Pasadena, California, United States, 91105 | |
United States, Maryland | |
University of Maryland, University of Maryland Medical Center | |
Baltimore, Maryland, United States, 21201 | |
United States, North Carolina | |
Duke University, Duke University Medical Center | |
Durham, North Carolina, United States, 27710 | |
United States, Pennsylvania | |
Fox Chase Cancer Center | |
Philadelphia, Pennsylvania, United States, 19111 | |
China, Jiangsu | |
Chinese Nanjing Bayi Hospital | |
Nanjing, Jiangsu, China, 210002 | |
China, Tianjin | |
Tianjin Union Medicine Center | |
Tianjin, Tianjin, China, 300121 | |
China | |
Cancer Hospital, Academy of Med Science and Peking Union Med | |
Beijing, China, 100021 | |
307 Hospital of Chinese People's Liberation Army | |
Beijing, China, 100071 | |
Chinese PLA General Hospital | |
Beijing, China, 100853 | |
France | |
Institut Curie | |
Paris, France, 75005 | |
Centre Rene Gauducheau | |
Saint-Herblain, France, 44805 | |
Switzerland | |
Centre Hospitalier Universitaire Vaudois | |
Lausanne, Switzerland, CH-1011 |
Study Director: | Puma | Biotechnology |
Responsible Party: | Puma Biotechnology, Inc. |
ClinicalTrials.gov Identifier: | NCT00398567 |
Other Study ID Numbers: |
3144A1-202 / B1891013 |
First Posted: | November 10, 2006 Key Record Dates |
Results First Posted: | April 13, 2018 |
Last Update Posted: | July 24, 2018 |
Last Verified: | June 2018 |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
HKI-272 neratinib trastuzumab breast cancer |
Nerlynx PB-272 HER2 |
Breast Neoplasms Neoplasms by Site Neoplasms Breast Diseases |
Skin Diseases Trastuzumab Antineoplastic Agents, Immunological Antineoplastic Agents |