Advanced Breast CancerPhase 1/2NCT00398567
A Phase 1/2 Study Of HKI-272 (Neratinib) in Combination With Trastuzumab (Herceptin) In Subjects With Advanced Breast Cancer
A Phase 1/2 study testing HKI-272 and trastuzumab in people with Advanced Breast Cancer, run by Puma Biotechnology, Inc. at 14 sites in 4 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Breast Cancer
- What is being tested?
- HKI-272 and trastuzumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 14 sitesin 4 countries
- Study dates
- 4 Apr 2007to 2 Mar 2018
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 12Show fewer
- 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
Trial locations and contacts
14 sites in 4 countries.
14 sites in 4 countries
United States6 sites
University of Maryland, University of Maryland Medical Center
Baltimore, Maryland, 21201
City of Hope National Medical Center
Duarte, California, 91010-3000
Duke University, Duke University Medical Center
Durham, North Carolina, 27710
LAC/USC Medical Center, USC/Norris Comprehensive Cancer Center
Los Angeles, California, 90033
City of Hope National Medical Center
Pasadena, California, 91105
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
China5 sites
Cancer Hospital, Academy of Med Science and Peking Union Med
Beijing, 100021
307 Hospital of Chinese People's Liberation Army
Beijing, 100071
Chinese PLA General Hospital
Beijing, 100853
Chinese Nanjing Bayi Hospital
Nanjing, Jiangsu, 210002
Tianjin Union Medicine Center
Tianjin, Tianjin Municipality, 300121
France2 sites
Institut Curie
Paris, 75005
Centre Rene Gauducheau
Saint-Herblain, 44805
Switzerland1 site
Centre Hospitalier Universitaire Vaudois
Lausanne, CH-1011
About this study
Official title: A Phase I/II Study of HKI-272 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.
Read the detailed description
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.
- Conditions
- Advanced Breast Cancer
- Being tested
- HKI-272, trastuzumab
- Keywords
- HKI-272, neratinib, trastuzumab, breast cancer, Nerlynx, PB-272, HER2
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HKI-272Drug
Also called neratinib
HKI-272 by mouth
trastuzumabDrug
Also called Herceptin
trastuzumab 4 mg/kg IV as a loading dose followed by trastuzumab 2 mg/kg weekly thereafter
| Study group | Role | What they receive |
|---|---|---|
| Part 1 - dose level 1 (160 mg) | Experimental | All subjects receiving HKI-272 dose level 1 in combination with trastuzumab Receives: Drug: HKI-272; Drug: trastuzumab |
| Part 1 - dose level 2 (240 mg) | Experimental | All subjects receiving HKI-272 dose level 2 in combination with trastuzumab Receives: Drug: HKI-272; Drug: trastuzumab |
| Part 2 - expanded MTD cohort | Experimental | All subjects receiving HKI-272 in combination with trastuzumab Receives: Drug: HKI-272; Drug: trastuzumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From first dose date to progression status (PD or death) at 16-week
Secondary outcomes (6)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: From first dose date to progression or last tumor assessment, assessed up to five and half years.
Area Under the Curve of Neratinib Concentration
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.
Measured: Prior to the first dose, and at hours 1, 2, 4, 6, 8 and 24 on days 22.
Terminal-phase Elimination Half-life of Neratinib in Combination With Trastuzumab.
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.
Measured: Prior to the first dose, on days 22 through 23 of month 1, and on day 1 in months 2 through 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Nov 2006 (estimated)
- Study start4 Apr 2007
- Primary completion31 Jul 2009
- Study completion2 Mar 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Advanced Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- Puma Biotechnology, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Puma, Study director, Biotechnology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00398567
- Sponsor's protocol ID
- 3144A1-202 / B1891013
- Status last verified
- Jun 2018
- First submitted
- 9 Nov 2006
- Last updated
- 24 Jul 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Study of HKI-272 in Combination With Trastuzumab (Herceptin) in Subjects With Advanced Breast Cancer
- ClinicalTrials.gov ID
- NCT00398567
- Acronym / sponsor ID
- 3144A1-202 / B1891013
- Conditions
- Advanced Breast Cancer
- Keywords
- HKI-272, neratinib, trastuzumab, breast cancer, Nerlynx, PB-272, HER2
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- Puma Biotechnology, Inc.Industry (pharma, biotech, devices)
- Study start
- 4 Apr 2007 (actual)
- Primary completion
- 31 Jul 2009 (actual)
- Study completion
- 2 Mar 2018 (actual)
- First posted
- 10 Nov 2006 (estimated)
- Results
- Posted 13 Apr 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Part 1 - dose level 1 (160 mg) | Experimental | Drug: HKI-272, Drug: trastuzumabAll subjects receiving HKI-272 dose level 1 in combination with trastuzumab |
| Part 1 - dose level 2 (240 mg) | Experimental | Drug: HKI-272, Drug: trastuzumabAll subjects receiving HKI-272 dose level 2 in combination with trastuzumab |
| Part 2 - expanded MTD cohort | Experimental | Drug: HKI-272, Drug: trastuzumabAll subjects receiving HKI-272 in combination with trastuzumab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HKI-272Also: neratinibHKI-272 by mouth | Drug | Part 1 - dose level 1 (160 mg), Part 1 - dose level 2 (240 mg), Part 2 - expanded MTD cohort |
| trastuzumabAlso: Herceptintrastuzumab 4 mg/kg IV as a loading dose followed by trastuzumab 2 mg/kg weekly thereafter | Drug | Part 1 - dose level 1 (160 mg), Part 1 - dose level 2 (240 mg), Part 2 - expanded MTD cohort |
Primary outcome
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.
6 secondary outcomes
Objective Response Rate (ORR)
Time frame: From first dose date to progression or last tumor assessment, up to five and a half years.
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
Progression Free Survival (PFS)
Time frame: From first dose date to progression or death, assessed up to five and half years.
Clinical Benefit Rate (CBR)
Time frame: From first dose date to progression or last tumor assessment, assessed up to five and half years.
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.
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jul 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Puma study director
Biotechnology
14 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing HKI-272 and trastuzumab in people with Advanced Breast Cancer, run by Puma Biotechnology, Inc. at 14 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in United States, China, France, Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Apr 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
16-week Progression-free Survival (PFS) Rate (time frame: From first dose date to progression status (PD or death) at 16-week). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jul 2018.