Breast CancerPhase 1/2NCT00706030
Study Evaluating Neratinib (HKI-272) In Combination With Vinorelbine In Subjects With Solid Tumors And Metastatic Breast Cancer
A Phase 1/2 study testing neratinib and vinorelbine in people with Breast Cancer and Advanced Malignant Solid Tumors, run by Puma Biotechnology, Inc. at 35 sites in 11 countries.
Trial summary
The purpose of this study is to identify the highest tolerable dose of neratinib (HKI-272) in combination with vinorelbine and to assess the safety of the combination of the two drugs as well as to obtain preliminary information on whether the combination of the two drugs has any effect on solid tumors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer, Advanced Malignant Solid Tumors
- What is being tested?
- neratinib and vinorelbine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 92 participants
- Where
- 35 sitesin 11 countries
- Study dates
- 29 Apr 2008to 7 Jun 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
- Confirmed pathologic diagnosis of a solid tumor that is not curable with available therapies for which HKI-272 plus vinorelbine is a reasonable treatment option (part 1 only) or Confirmed pathologic diagnosis of ErbB-2-positive breast cancer (current stage IV) in female subjects for which vinorelbine plus HKI-272 is a reasonable treatment option (part 2 only).
- At least 1 prior antineoplastic chemotherapy treatment regimen for metastatic disease and at least 1 prior treatment with a trastuzumab-containing regimen for at least 6 weeks, for metastatic disease or subject relapsing under adjuvant treatment (part 2 only).
- At least 1 measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST).
Who cannot join
- More than 2 prior antineoplastic treatment regimens (excluding hormonotherapy) for metastatic disease. Subjects who relapsed under adjuvant treatment shouldn't have received more than one line of chemotherapy for metastatic disease (part 2 only).
- Prior treatment with vinorelbine for metastatic setting, or prior treatment with any ErbB-2 targeted agents except trastuzumab (part 2 only). Up to 20 subjects with ErbB-2-overexpressing metastatic breast cancer who have been previously exposed to lapatinib but are not refractory to lapatinib may be enrolled in part 2.
- Prior treatment with anthracyclines with a cumulative dose of doxorubicin of greater than 400 mg/m2, or of epirubicin dose of greater than 800 mg/m2, or the equivalent dose for other anthracyclines or derivatives (part 2 only).
Trial locations and contacts
35 sites in 11 countries.
35 sites in 11 countries
United States8 sites
Carolinas Hematology-Oncology Associates
Charlotte, North Carolina, 28203
City of Hope National Medical Center
Duarte, California, 91010
Highlands Oncology Group
Fayetteville, Arkansas, 72703
Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, 03756
Columbia University Medical Center
New York, New York, 10032
Hematology Oncology Associates of Rockland
Nyack, New York, 10960
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
Albert Einstein Cancer Center
The Bronx, New York, 10461
United Kingdom5 sites
Velindre Cancer Centre
Cardiff, CF14 2TL
Broomfield Hospital
Chelmsford, Essex, CM1 7ET
Guy's and St. Thomas' NHS Foundation Trust, Guy's Hospital
London, SE1 9RT
Christie NHS Foundation Trust
Manchester, Lancashire, M20 4BX
Southampton General Hospital
Southampton, Hampshire, SO16 6YD
China4 sites
Cancer Hospital, Chinese Academy of Medical Sciences
Beijing, Beijing Municipality, 100021
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
Tianjin Cancer Hospital
Tianjin, Tianjin Municipality, 300060
France4 sites
Centre Paul Papin
Angers, 49100
Institut Paoli Calmette
Marseille, 13272
Institut Curie, Département d'Oncologie Médicale
Paris, 75248
Institut Claudius Regaud
Toulouse, 31052
Spain4 sites
Centro Oncologico de Galicia
A Coruña, 15009
Hospital Clinic i Provincial de Barcelona
Barcelona, 08036
Hospital Arnau de Vilanova, Servicio de Oncologia Medica
Lleida, 25198
Hospital 12 de Octubre, Servicio de Oncologia Medica
Madrid, 28041
Belgium3 sites
AZ Klina Brasschaat
Brasschaat, 2930
Institut Jules Bordet
Brussels, 1000
St.-Augustinus Hospital Oncology Department
Wilrijk, 2610
Hong Kong2 sites
Queen Mary Hospital
Hong Kong
UNIMED Medical Institute
Hong Kong
Poland2 sites
Centrum Onkologii Ziemii Lubelskiej, Oddział Chemioterapii
Lublin, 20-090
Wojskowy Instytut Medyczny, Klinika Onkologii
Warsaw, 00-909
Netherlands1 site
Martini Ziekenhuis / Afdeling Interne Geneeskunde
Groningen, 9728 NZ
About this study
Official title: A Phase 1/2 Study Of HKI-272 In Combination With Vinorelbine In Subjects With Solid Tumors And Metastatic Breast Cancer
The purpose of this study is to identify the highest tolerable dose of neratinib (HKI-272) in combination with vinorelbine and to assess the safety of the combination of the two drugs as well as to obtain preliminary information on whether the combination of the two drugs has any effect on solid tumors.
The study will be conducted in two parts. In the first part, testing will be done on up to 12 subjects to determine the highest tolerable dose of HKI-272 and vinorelbine in patients with advanced solid tumors. In the second part of the study, approximately 60 additional subjects with metastatic ErbB-2-positive breast cancer, with no prior exposure to lapatinib, are planned to be added to better define the tolerability and preliminary activity of HKI-272 in combination with vinorelbine. Up to 20 additional subjects with ErbB-2-positive breast cancer with prior lapatinib exposure are also planned to be enrolled in part 2 for exploratory analyses.
- Conditions
- Breast Cancer, Advanced Malignant Solid Tumors
- Being tested
- neratinib, vinorelbine
- Keywords
- Metastatic breast cancer, HKI-272, Neratinib, Nerlynx, PB-272
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
neratinibDrug
Also called HKI-272, Nerlynx
vinorelbineDrug
| Study group | Role | What they receive |
|---|---|---|
| neratinib 160 mg + vinorelbine | Experimental | neratinib 160 mg tablets administered daily by mouth, vinorelbine 25 mg/m^2 administered IV on day 1 and day 8 of 21 day cycle Receives: Drug: neratinib; Drug: vinorelbine |
| neratinib 240 mg + vinorelbine | Experimental | neratinib 240 mg tablets administered daily by mouth, vinorelbine 25 mg/m^2 administered IV on day 1 and day 8 of 21 day cycle Receives: Drug: neratinib; Drug: vinorelbine |
| neratinib 240 mg + vinorelbine, No Prior Lapatinib | Experimental | neratinib 240 mg tablets administered daily by mouth, vinorelbine 25 mg/m^2 administered IV on day 1 and day 8 of 21 day cycle Receives: Drug: neratinib; Drug: vinorelbine |
| neratinib 240 mg + vinorelbine, Prior Lapatinib | Experimental | neratinib 240 mg tablets administered daily by mouth, vinorelbine 25 mg/m^2 administered IV on day 1 and day 8 of 21 day cycle Receives: Drug: neratinib; Drug: vinorelbine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate
Overall Response Rate (ORR), subjects with CR or PR by independent review in subjects with ErbB-2-positive breast cancer treated at the MTD of neratinib in combination with vinorelbine per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.0: 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 four years and six months.
Maximum Tolerated Dose
Maximum Tolerated Dose (MTD) of Neratinib in combination with vinorelbine in subjects with advanced solid tumors.
Measured: From Day 1 to Day 21.
Secondary outcomes (3)
Clinical Benefit Rate
Percentage of participants with partial response (PR) or complete response (CR) or stable disease > 24 weeks by independent assessment for subjects with ErbB-2-positive breast cancer treated at the MTD of neratinib in combination with vinorelbine, 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 four years and six months.
Progression-Free Survival
Number of weeks between the date of the first dose of test article and the first date of disease recurrence or progression, or death due to any cause, was documented, censored at the last evaluation, investigator assessment. Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria (v1.0), as at least a 20% increase in the sum of the longest diameters (LD) of target lesions, taking as reference the nadir LD, meaning the smallest sum of the LDs recorded since the treatment started; or unequivocal progression of existing nontarget lesions; or the appearance of any new lesions.
Measured: From first dose date to progression or death, up to four years and six months.
Duration Of Response
Duration of response for subjects who had complete or partial response from first response to disease progression, death or last assessment per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.0: 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 start date of response to first PD/death, up to four years and six months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2008 (estimated)
- Study start29 Apr 2008
- Primary completionOct 2009
- Study completion7 Jun 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 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
- Sequential
- Masking
- None (open label)
- Enrolment
- 92 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
- NCT00706030
- Sponsor's protocol ID
- 3144A1-2204 / B1891015
- Status last verified
- Jun 2018
- First submitted
- 25 Jun 2008
- Last updated
- 9 Aug 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Awada A, Dirix L, Manso Sanchez L, Xu B, Luu T, Dieras V, Hershman DL, Agrapart V, Ananthakrishnan R, Staroslawska E. Safety and efficacy of neratinib (HKI-272) plus vinorelbine in the treatment of patients with ErbB2-positive metastatic breast cancer pretreated with anti-HER2 therapy. Ann Oncol. 2013 Jan;24(1):109-16. doi: 10.1093/annonc/mds284. Epub 2012 Sep 11.
PubMed 22967996
Study at a glance
From the registry record, last updated by the sponsor on 9 Aug 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 Vinorelbine In Subjects With Solid Tumors And Metastatic Breast Cancer
- ClinicalTrials.gov ID
- NCT00706030
- Acronym / sponsor ID
- 3144A1-2204 / B1891015
- Conditions
- Breast Cancer, Advanced Malignant Solid Tumors
- Keywords
- Metastatic breast cancer, HKI-272, Neratinib, Nerlynx, PB-272
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 92 participants (actual)
- Lead sponsor
- Puma Biotechnology, Inc.Industry (pharma, biotech, devices)
- Study start
- 29 Apr 2008 (actual)
- Primary completion
- Oct 2009 (actual)
- Study completion
- 7 Jun 2018 (actual)
- First posted
- 27 Jun 2008 (estimated)
- Results
- Posted 8 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 identify the highest tolerable dose of neratinib (HKI-272) in combination with vinorelbine and to assess the safety of the combination of the two drugs as well as to obtain preliminary information on whether the combination of the two drugs has any effect on solid tumors.
The study will be conducted in two parts. In the first part, testing will be done on up to 12 subjects to determine the highest tolerable dose of HKI-272 and vinorelbine in patients with advanced solid tumors. In the second part of the study, approximately 60 additional subjects with metastatic ErbB-2-positive breast cancer, with no prior exposure to lapatinib, are planned to be added to better define the tolerability and preliminary activity of HKI-272 in combination with vinorelbine. Up to 20 additional subjects with ErbB-2-positive breast cancer with prior lapatinib exposure are also planned to be enrolled in part 2 for exploratory analyses.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| neratinib 160 mg + vinorelbine | Experimental | Drug: neratinib, Drug: vinorelbineneratinib 160 mg tablets administered daily by mouth, vinorelbine 25 mg/m^2 administered IV on day 1 and day 8 of 21 day cycle |
| neratinib 240 mg + vinorelbine | Experimental | Drug: neratinib, Drug: vinorelbineneratinib 240 mg tablets administered daily by mouth, vinorelbine 25 mg/m^2 administered IV on day 1 and day 8 of 21 day cycle |
| neratinib 240 mg + vinorelbine, No Prior Lapatinib | Experimental | Drug: neratinib, Drug: vinorelbineneratinib 240 mg tablets administered daily by mouth, vinorelbine 25 mg/m^2 administered IV on day 1 and day 8 of 21 day cycle |
| neratinib 240 mg + vinorelbine, Prior Lapatinib | Experimental | Drug: neratinib, Drug: vinorelbineneratinib 240 mg tablets administered daily by mouth, vinorelbine 25 mg/m^2 administered IV on day 1 and day 8 of 21 day cycle |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Confirmed pathologic diagnosis of a solid tumor that is not curable with available therapies for which HKI-272 plus vinorelbine is a reasonable treatment option (part 1 only) or Confirmed pathologic diagnosis of ErbB-2-positive breast cancer (current stage IV) in female subjects for which vinorelbine plus HKI-272 is a reasonable treatment option (part 2 only).
- At least 1 prior antineoplastic chemotherapy treatment regimen for metastatic disease and at least 1 prior treatment with a trastuzumab-containing regimen for at least 6 weeks, for metastatic disease or subject relapsing under adjuvant treatment (part 2 only).
- At least 1 measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST).
Key exclusion criteria (3 listed)
- More than 2 prior antineoplastic treatment regimens (excluding hormonotherapy) for metastatic disease. Subjects who relapsed under adjuvant treatment shouldn't have received more than one line of chemotherapy for metastatic disease (part 2 only).
- Prior treatment with vinorelbine for metastatic setting, or prior treatment with any ErbB-2 targeted agents except trastuzumab (part 2 only). Up to 20 subjects with ErbB-2-overexpressing metastatic breast cancer who have been previously exposed to lapatinib but are not refractory to lapatinib may be enrolled in part 2.
- Prior treatment with anthracyclines with a cumulative dose of doxorubicin of greater than 400 mg/m2, or of epirubicin dose of greater than 800 mg/m2, or the equivalent dose for other anthracyclines or derivatives (part 2 only).
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 |
|---|---|---|
| neratinibAlso: HKI-272, Nerlynx | Drug | neratinib 160 mg + vinorelbine, neratinib 240 mg + vinorelbine, neratinib 240 mg + vinorelbine, No Prior Lapatinib, neratinib 240 mg + vinorelbine, Prior Lapatinib |
| vinorelbine | Drug | neratinib 160 mg + vinorelbine, neratinib 240 mg + vinorelbine, neratinib 240 mg + vinorelbine, No Prior Lapatinib, neratinib 240 mg + vinorelbine, Prior Lapatinib |
Primary outcome
Overall Response Rate
Time frame: From first dose date to progression or last tumor assessment, up to four years and six months.
Overall Response Rate (ORR), subjects with CR or PR by independent review in subjects with ErbB-2-positive breast cancer treated at the MTD of neratinib in combination with vinorelbine per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.0: 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.
Maximum Tolerated Dose
Time frame: From Day 1 to Day 21.
Maximum Tolerated Dose (MTD) of Neratinib in combination with vinorelbine in subjects with advanced solid tumors.
3 secondary outcomes
Clinical Benefit Rate
Time frame: From first dose date to progression or last tumor assessment, up to four years and six months.
Progression-Free Survival
Time frame: From first dose date to progression or death, up to four years and six months.
Duration Of Response
Time frame: From start date of response to first PD/death, up to four years and six months.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Aug 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 22967996Awada A, Dirix L, Manso Sanchez L, Xu B, Luu T, Dieras V, Hershman DL, Agrapart V, Ananthakrishnan R, Staroslawska E. Safety and efficacy of neratinib (HKI-272) plus vinorelbine in the treatment of patients with ErbB2-positive metastatic breast cancer pretreated with anti-HER2 therapy. Ann Oncol. 2013 Jan;24(1):109-16. doi: 10.1093/annonc/mds284. Epub 2012 Sep 11.
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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
35 sites in 11 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing neratinib and vinorelbine in people with Breast Cancer and Advanced Malignant Solid Tumors, run by Puma Biotechnology, Inc. at 35 sites in 11 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 3 inclusion and 3 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 9 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 35 sites in United States, United Kingdom, China, France, Spain and 6 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 8 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?
Overall Response Rate (time frame: From first dose date to progression or last tumor assessment, up to four years and six months.). The study lists 2 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 NCT00706030, 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 9 Aug 2018.