Advanced Breast CancerPhase 1/2NCT00445458
A Phase 1/2 Study of HKI-272 (Neratinib) in Combination With Paclitaxel (Taxol) in Subjects With Solid Tumors and Breast Cancer
A Phase 1/2 study testing HKI-272 and Paclitaxel in people with Advanced Breast Cancer and Advanced Malignant Solid Tumors, run by Puma Biotechnology, Inc. at 32 sites in 9 countries.
Trial summary
The purpose of this study is to learn whether it is safe and effective to administer HKI-272 (neratinib) in combination with paclitaxel in patients with breast cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Breast Cancer, Advanced Malignant Solid Tumors, Breast Neoplasms
- What is being tested?
- HKI-272 and Paclitaxel
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 110 participants
- Where
- 32 sitesin 9 countries
- Study dates
- 11 Sep 2007to 7 Feb 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
- Good performance status
- Normal ejection fraction
- Adequate cardiac, kidney, and liver function
- Adequate blood counts
- At least one measurable target lesion
- Negative pregnancy test for female subjects
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- Pathologically confirmed solid tumor not curable with available standard therapy
- Pathologically confirmed breast cancer
- HER2 positive tumor
- Prior treatment with Herceptin
Who cannot join
- Major surgery, radiotherapy, chemotherapy or investigational agents within two weeks of treatment day 1
- Subjects with bone or skin as the only site of disease
- Active central nervous system metastases
- Significant cardiac disease or dysfunction
- Significant gastrointestinal disorder
- Inability or unwillingness to swallow HKI-272 capsules
Show all 14Show fewer
- Prior exposure to HKI-272 or other HER2 targeted agents, except trastuzumab (Part 2 only). Prior lapatinib is permitted in arm B of part 2.
- Treatment with a taxane within 3 months of treatment day 1
- Grade 2 or greater motor or sensory neuropathy
- Pregnant or breast feeding women
- Known hypersensitivity to paclitaxel or Cremophor EL
- Prior treatment with anthracyclines with cumulative dose of >400 mg/m^2
- 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
- More than 1 (arm A) or 3 (arm B) prior cytotoxic chemotherapy regimen for metastatic disease
Trial locations and contacts
32 sites in 9 countries.
32 sites in 9 countries
United States8 sites
Boston University Medical Center
Boston, Massachusetts, 02118
Scripps, Clinic General
La Jolla, California, 92037
Moores UC San Diego Cancer Center
La Jolla, California, 92093
Mid-Michigan Physicians-HOS Division
Lansing, Michigan, 48912
Columbia University Medical Center
New York, New York, 10032
Oncology Care Associates
Saint Joseph, Michigan, 49085
CTRC at The University of Texas Health Science Center
San Antonio, Texas, 78229
Sharp Memorial Hospital
San Diego, California, 92123
China6 sites
The Hospital Affiliated Academy Military Medical Science, Chinese People's Liberation Army
Beijing, Beijing Municipality, 100071
Chinese People's Liberation Army General Hospital
Beijing, Beijing Municipality, 100853
Cancer Hospital, Chinese Academy of Medical Sciences
Beijing, 100021
Peking Union Medical College Hospital of Chinese Academy of Medical Sciences
Beijing, 100032
Tianjin Cancer Hospital
Tianjin, Tianjin Municipality, 300060
Tianjin Union Medicine Center Department of Oncology
Tianjin, Tianjin Municipality, 300121
Belgium4 sites
Institut Jules Bordet Unite du Chimiotherapie
Brussels, 1000
Universitair Ziekenhuis Gent
Ghent, 9000
AZ Groeninge Campus Maria's Voorzienigheid (MV)
Kortrijk, 8500
Oncologisch Centrum GZA - Location St Augustinus
Wilrijk, 2610
India4 sites
Birla Cancer Centre, S.M.S. Medical College & Hospital
Jaipur, Rajasthan, 302004
Tata Memorial Hospital
Mumbai, Parel, 400012
Jehangir Clinical Development Centre, Jehangir Hospital Premises
Pune, Maharashtra, 411001
M.M.F. Joshi Hospital & Ratna Memorial Hospital
Pune, Maharashtra, 411004
Hong Kong3 sites
UNIMED Medical Institute
Hong Kong, 0
Department of Medicine, Queen Mary Hospital
Hong Kong
Department of Surgery Queen Mary Hospital
Hong Kong
Poland2 sites
Wojewodzki Szpital Specjalistyczny im. Ludwika Rydygiera, Oddzial Onkologii
Krakow, 31-826
Oddzial Chemioterapii Centrum Onkologii Ziemii Lubelskiej
Lublin, 20-090
South Korea2 sites
Yonsei University Health System - Severance Hospital
Seoul, 120-752
Asan Medical Center, Division of Oncology, Department of Internal Medicine
Seoul, 138-736
Ukraine2 sites
City Multifield Clinical Hospital #4 Department of chemotherapy, Dnipropetrovs'k State Medical Academy, Chair of Oncology and Medical Radiology
Dnipropetrovsk, 49102
State Oncological Regional Treatment and Diagnostic Center Department of chemotherapy
Lviv, 79031
Canada1 site
Princess Margaret Hospital University Health Network
Toronto, Ontario, M5G 2M9
About this study
Official title: A Phase 1/2 Study of HKI-272 in Combination With Paclitaxel in Subjects With Solid Tumors and Breast Cancer
The purpose of this study is to learn whether it is safe and effective to administer HKI-272 (neratinib) in combination with paclitaxel in patients with breast cancer.
- Being tested
- HKI-272, Paclitaxel
- Keywords
- cancer, HKI-272, neratinib, paclitaxel, Taxol, breast cancer, Nerlynx
- Medical subject headings
- Breast Neoplasms, 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
PaclitaxelDrug
| Study group | Role | What they receive |
|---|---|---|
| HKI-272 dose level 1 | Experimental | Part 1: Subjects with solid tumors receiving HKI-272 (neratinib) 160 mg daily by mouth in combination with paclitaxel 80 mg/m^2 weekly IV. Receives: Drug: HKI-272; Drug: Paclitaxel |
| HKI-272 dose level 2 | Experimental | Part 1: Subjects with solid tumors receiving HKI-272 (neratinib) 240 mg daily by mouth in combination with paclitaxel 80 mg/m^2 weekly IV. Receives: Drug: HKI-272; Drug: Paclitaxel |
| HKI-272 expanded MTD cohort, arm A | Experimental | Part 2: Subjects with metastatic breast cancer who have not received more than 1 prior cytotoxic chemotherapy treatment regimen for metastatic disease receiving HKI-272 (neratinib) 240 mg daily by mouth in combination with paclitaxel 80 mg/m^2 weekly IV. Receives: Drug: HKI-272; Drug: Paclitaxel |
| HKI-272 expanded MTD cohort, arm B | Experimental | Part 2: Subjects with metastatic breast cancer who have not received more than 3 prior cytotoxic chemotherapy treatment regimen for metastatic disease receiving HKI-272 (neratinib) 240 mg daily by mouth in combination with paclitaxel 80 mg/m^2 weekly IV. Receives: Drug: HKI-272; Drug: Paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose Limiting Toxicity Incidence of Neratinib in Combination With Paclitaxel
Dose Limiting Toxicity in subjects with solid tumors treated with neratinib, administered daily, in combination with paclitaxel 80 mg/m² IV on days 1, 8, and 15 of a 28 day cycle.
Measured: From first dose date through day 28
Maximum Tolerated Dose
Maximum Tolerated Dose (MTD) of neratinib, daily, in combination with paclitaxel 80 mg/m², intravenous at days 1, 8, and 15, associated with the dose limiting toxicity data.
Measured: From first dose date through day 28.
Objective Response Rate
Subjects with partial response (PR) or complete response (CR) with ERBB2 positive breast cancer treated at the maximum tolerated dose (MTD) of neratinib in combination with paclitaxel, per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v.1.0: CR, disappearance of all target lesions; PR, >=30% decrease in the sum of the longest diameter of target lesions; and no progressive disease (PD) for non-target lesions, and no new lesions.
Measured: From first dose date to progression or last tumor assessment, up to 140 weeks
Secondary outcomes (2)
Maximum Plasma Concentration of Neratinib
Maximum plasma concentration of neratinib; after each dosing of neratinib on Cycle 1 of Day 15, blood samples taken at regular time points.
Measured: Samples taken at 0 hour and at 1, 2, 4, 6, 8, and 24 hours postdose on Day 15 of Cycle 1, and 1 predose sample on Day 1 in Cycle 1.
Area Under the Concentration-time Curve 0-24
Area under the concentration-time curve of neratinib; after each dosing of neratinib on Cycle 1 of Day 15, blood samples taken at regular time points.
Measured: Samples taken at 0 hour and at 1, 2, 4, 6, 8, and 24 hours postdose on Day 15 of Cycle 1, and 1 predose sample on Day 1 in Cycle 1.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Mar 2007 (estimated)
- Study start11 Sep 2007
- Primary completionMay 2011
- Study completion7 Feb 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.
- Publications (1)Papers the sponsor has linked to this study.
- 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
- 110 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
- NCT00445458
- Sponsor's protocol ID
- 3144A1-203 / B1891014
- Status last verified
- Jun 2018
- First submitted
- 8 Mar 2007
- Last updated
- 26 Jul 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Chow LW, Xu B, Gupta S, Freyman A, Zhao Y, Abbas R, Vo Van ML, Bondarenko I. Combination neratinib (HKI-272) and paclitaxel therapy in patients with HER2-positive metastatic breast cancer. Br J Cancer. 2013 May 28;108(10):1985-93. doi: 10.1038/bjc.2013.178. Epub 2013 Apr 30.
PubMed 23632474
Study at a glance
From the registry record, last updated by the sponsor on 26 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2 Study of HKI-272 in Combination With Paclitaxel in Subjects With Solid Tumors and Breast Cancer
- ClinicalTrials.gov ID
- NCT00445458
- Acronym / sponsor ID
- 3144A1-203 / B1891014
- Keywords
- cancer, HKI-272, neratinib, paclitaxel, Taxol, breast cancer, Nerlynx
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 110 participants (actual)
- Lead sponsor
- Puma Biotechnology, Inc.Industry (pharma, biotech, devices)
- Study start
- 11 Sep 2007 (actual)
- Primary completion
- May 2011 (actual)
- Study completion
- 7 Feb 2018 (actual)
- First posted
- 9 Mar 2007 (estimated)
- Results
- Posted 9 May 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 learn whether it is safe and effective to administer HKI-272 (neratinib) in combination with paclitaxel in patients with breast cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| HKI-272 dose level 1 | Experimental | Drug: HKI-272, Drug: PaclitaxelPart 1: Subjects with solid tumors receiving HKI-272 (neratinib) 160 mg daily by mouth in combination with paclitaxel 80 mg/m^2 weekly IV. |
| HKI-272 dose level 2 | Experimental | Drug: HKI-272, Drug: PaclitaxelPart 1: Subjects with solid tumors receiving HKI-272 (neratinib) 240 mg daily by mouth in combination with paclitaxel 80 mg/m^2 weekly IV. |
| HKI-272 expanded MTD cohort, arm A | Experimental | Drug: HKI-272, Drug: PaclitaxelPart 2: Subjects with metastatic breast cancer who have not received more than 1 prior cytotoxic chemotherapy treatment regimen for metastatic disease receiving HKI-272 (neratinib) 240 mg daily by mouth in combination with paclitaxel 80 mg/m^2 weekly IV. |
| HKI-272 expanded MTD cohort, arm B | Experimental | Drug: HKI-272, Drug: PaclitaxelPart 2: Subjects with metastatic breast cancer who have not received more than 3 prior cytotoxic chemotherapy treatment regimen for metastatic disease receiving HKI-272 (neratinib) 240 mg daily by mouth in combination with paclitaxel 80 mg/m^2 weekly IV. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Good performance status
- Normal ejection fraction
- Adequate cardiac, kidney, and liver function
- Adequate blood counts
- At least one measurable target lesion
Key exclusion criteria (14 listed)
- Major surgery, radiotherapy, chemotherapy or investigational agents within two weeks of treatment day 1
- Subjects with bone or skin as the only site of disease
- Active central nervous system metastases
- Significant cardiac disease or dysfunction
- Significant gastrointestinal disorder
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: Neratinib | Drug | HKI-272 dose level 1, HKI-272 dose level 2, HKI-272 expanded MTD cohort, arm A, HKI-272 expanded MTD cohort, arm B |
| Paclitaxel | Drug | HKI-272 dose level 1, HKI-272 dose level 2, HKI-272 expanded MTD cohort, arm A, HKI-272 expanded MTD cohort, arm B |
Primary outcome
Dose Limiting Toxicity Incidence of Neratinib in Combination With Paclitaxel
Time frame: From first dose date through day 28
Dose Limiting Toxicity in subjects with solid tumors treated with neratinib, administered daily, in combination with paclitaxel 80 mg/m² IV on days 1, 8, and 15 of a 28 day cycle.
Maximum Tolerated Dose
Time frame: From first dose date through day 28.
Maximum Tolerated Dose (MTD) of neratinib, daily, in combination with paclitaxel 80 mg/m², intravenous at days 1, 8, and 15, associated with the dose limiting toxicity data.
Objective Response Rate
Time frame: From first dose date to progression or last tumor assessment, up to 140 weeks
Subjects with partial response (PR) or complete response (CR) with ERBB2 positive breast cancer treated at the maximum tolerated dose (MTD) of neratinib in combination with paclitaxel, per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v.1.0: CR, disappearance of all target lesions; PR, >=30% decrease in the sum of the longest diameter of target lesions; and no progressive disease (PD) for non-target lesions, and no new lesions.
2 secondary outcomes
Maximum Plasma Concentration of Neratinib
Time frame: Samples taken at 0 hour and at 1, 2, 4, 6, 8, and 24 hours postdose on Day 15 of Cycle 1, and 1 predose sample on Day 1 in Cycle 1.
Area Under the Concentration-time Curve 0-24
Time frame: Samples taken at 0 hour and at 1, 2, 4, 6, 8, and 24 hours postdose on Day 15 of Cycle 1, and 1 predose sample on Day 1 in Cycle 1.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jul 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 23632474Chow LW, Xu B, Gupta S, Freyman A, Zhao Y, Abbas R, Vo Van ML, Bondarenko I. Combination neratinib (HKI-272) and paclitaxel therapy in patients with HER2-positive metastatic breast cancer. Br J Cancer. 2013 May 28;108(10):1985-93. doi: 10.1038/bjc.2013.178. Epub 2013 Apr 30.
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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
32 sites in 9 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 Paclitaxel in people with Advanced Breast Cancer and Advanced Malignant Solid Tumors, run by Puma Biotechnology, Inc. at 32 sites in 9 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 10 inclusion and 14 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 26 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 32 sites in United States, China, Belgium, India, Hong Kong and 4 more countries. 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 9 May 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?
Dose Limiting Toxicity Incidence of Neratinib in Combination With Paclitaxel (time frame: From first dose date through day 28). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00445458, which also lists 1 linked publication.
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 26 Jul 2018.