Solid TumorPhase 1NCT02593708
Phase1 of Neratinib+Trastuzumab, Pertuzumab, Paclitaxel in Patients With Advanced Solid Tumors/HER2+
A Phase 1 study testing Neratinib, Paclitaxel and Pertuzumab in people with Solid Tumor, run by Michelle Melisko at 1 site in United States.
Trial summary
Open label, non-randomized, dose escalation and expansion Phase Ia/b trial to evaluate the safety and tolerability of the combination of neratinib plus paclitaxel, trastuzumab and pertuzumab to determine the recommended Phase II/III dose of this combination. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumor
- What is being tested?
- Neratinib, Paclitaxel and Pertuzumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Nov 2015to 31 Jul 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- Women and men 18 years or older with advanced solid tumor malignancy
- Ability to understand and voluntarily sign informed consent prior to undergoing any study-related assessments or procedures, as well as adhere to the study visit schedule and other protocol requirements.
- Local histologic or cytologic confirmation of HER2+ solid tumors by FISH amplification or IHC (3+)
- Patients must have received one prior approved therapy for metastatic disease and have not curable options
- For escalation: Documentation by established staging studies or clinical examination to have measurable or non-measurable metastatic disease per RECIST v1.1 criteria.
- For expansion: Documentation by established staging studies or clinical examination to have measurable metastatic disease per RECIST v1.1 criteria.
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- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.
- Adequate organ function:
- Absolute neutrophil count (ANC) ≥ 1.5 X 109/L
- Hemoglobin (Hgb) ≥9g/dL
- Platelets (plt) ≥ 100 x 109/L
- Potassium within normal range, or correctable with supplements;
- Serum calcium and magnesium within the normal range (or corrected with supplements)
- AST and ALT ≤2.5 x Upper Limit Normal (ULN)
- Serum total bilirubin ≤ 1.5 x ULN
- Serum creatinine ≤ 1.5 x ULN, or 24-hr clearance ≥ 60ml/min
- Serum albumin > 3.0 g/dL
- Left ventricular ejection fraction of >55% (or institutional lower normal value)
- Females of child-bearing potential (FCBP) must have negative serum pregnancy test within 7 days before starting study treatment and willingness to adhere to acceptable forms or birth control (a physician- approved contraceptive method: oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner)
- FCBP is defined as a sexually mature women who:
- Have not undergone a hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy (the surgical removal of both ovaries) or,
- Have not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time during the preceding 12 consecutive months
- Must be willing to practice abstinence or use highly effective contraception for a minimum of 6 months following completion of study treatment (in addition to during study therapy)
- Male subjects with female partner of childbearing potential must agree to the use of a physician-approved contraceptive method throughout the course of the study and for 3 months after the last dose of the investigational product.
- Ability to take oral medications
Who cannot join
- Any significant medical condition, laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
- Any condition that confounds the ability to interpret data from the study.
- Patients must have recovered from side effects from prior cancer-directed therapy to grade 1 or less (unless deemed not clinically significant by study investigator).
- Symptomatic central nervous system metastases. Subjects with brain metastases that have been previously treated and are stable for 4 weeks are allowed.
- Persistent diarrhea or malabsorption ≥ NCI CTCAE grade 1, despite medical management, ulcerative colitis, inflammatory bowel disease, resection of the stomach or small bowel, or other disease or condition significantly affecting gastrointestinal function.
- Unstable angina, significant cardiac arrhythmia, or New York Heart Association (NYHA) class III or IV congestive heart failure.
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- Grade 2 or higher neuropathy
- Known history of: cardiac disease, heart failure or decreased left ventricular ejection fraction, significant clinical arrhythmias
- Prior systemic cancer-directed treatments or investigational modalities ≤ 5 half lives or 4 weeks, whichever is shorter, prior to starting study drug or who have not recovered from grade 2 or higher side effects of such therapy (except alopecia).
- Major surgery ≤ 2 weeks prior to starting a study drug or who have not recovered from side effects of such therapy.
- Known allergic reaction to neratinib, pertuzumab, trastuzumab, paclitaxel, or any of their components.
- Women who are pregnant or breast-feeding.
- Known active Human Immunodeficiency Virus (HIV) infection, Hepatitis B or C.
Trial locations and contacts
1 site in 1 country.
United States1 site
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, 94115
About this study
Official title: Phase I Study to Evaluate the Safety of Neratinib in Combination With Paclitaxel, Trastuzumab and Pertuzumab in Women and Men With Advanced or Metastatic HER2+ Solid Tumors
Open label, non-randomized, dose escalation and expansion Phase Ia/b trial to evaluate the safety and tolerability of the combination of neratinib plus paclitaxel, trastuzumab and pertuzumab to determine the recommended Phase II/III dose of this combination.
Neratinib will be given once daily days 1-21 and should be taken orally with food. Paclitaxel and trastuzumab will be given IV on days 1, 8, and 15 out of 21 day cycles. Pertuzumab will be given IV every 3 weeks on day 1 out of 21-day cycles. Each cycle will be 21 days in duration.
Patients will continue on treatment until disease progression or intolerable toxicity.
Read the detailed description
Neratinib is a potent, irreversible, small molecule panErbB inhibitor of EGFR, HER2 and HER4 tyrosine kinases. Its activity prevents the autophosphorylation of HER2 and thus halts the downstream activation of this key proliferative pathway in tumors dependent on HER2 overexpression or EGFR activation. It has shown promising clinical activity in women with HER2+ stage 2 and 3 breast cancer in the neoadjuvant setting (I-SPY 2 TRIAL) and in women with stage 4 metastatic breast cancer, although evaluation in larger phase 3 trials is required to confirm these results.
The rationale for this study is to determine the feasibility of adding neratinib to a taxane based chemotherapy and the approved HER2 antagonists, trastuzumab and pertuzumab.
The study will evaluate the safety and tolerability and recommended dose of daily neratinib in combination with weekly paclitaxel, trastuzumab and tri-weekly pertuzumab in patients with HER2+ advanced or metastatic disease and, if successful, determine an optimal dose to move into phase II/III testing of this combination in the neoadjuvant setting.
- Conditions
- Solid Tumor
- Being tested
- Neratinib, Paclitaxel, Pertuzumab, Trastuzumab
- Keywords
- HER2+
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NeratinibDrug
PaclitaxelDrug
PertuzumabDrug
TrastuzumabDrug
| Study group | Role | What they receive |
|---|---|---|
| Cohort 0 | Experimental | 1. Neratinib: 80 mg, daily, oral
2. Paclitaxel: 80 mg/m2, weekly, intravenously
3. Pertuzumab: 840 mg loading dose, 420 mg every 3 weeks, intravenously
4. Trastuzumab: 4 mg/kg loading dose, 2mg/kg every week, intravenously Receives: Drug: Neratinib; Drug: Paclitaxel; Drug: Pertuzumab; Drug: Trastuzumab |
| Cohort 1 | Experimental | 1. Neratinib: 120 mg, daily, oral
2. Paclitaxel: 80 mg/m2, weekly, intravenously
3. Pertuzumab: 840 mg loading dose, 420 mg every 3 weeks, intravenously
4. Trastuzumab: 4 mg/kg loading dose, 2mg/kg every week, intravenously Receives: Drug: Neratinib; Drug: Paclitaxel; Drug: Pertuzumab; Drug: Trastuzumab |
| Cohort 2 | Experimental | 1. Neratinib: 160 mg, daily, oral
2. Paclitaxel: 80 mg/m2, weekly, intravenously
3. Pertuzumab: 840 mg loading dose, 420 mg every 3 weeks, intravenously
4. Trastuzumab: 4 mg/kg loading dose, 2mg/kg every week, intravenously Receives: Drug: Neratinib; Drug: Paclitaxel; Drug: Pertuzumab; Drug: Trastuzumab |
| Cohort 3 | Experimental | 1. Neratinib: 200 mg, daily, oral
2. Paclitaxel: 80 mg/m2, weekly, intravenously
3. Pertuzumab: 840 mg loading dose, 420 mg every 3 weeks, intravenously
4. Trastuzumab: 4 mg/kg loading dose, 2mg/kg every week, intravenously Receives: Drug: Neratinib; Drug: Paclitaxel; Drug: Pertuzumab; Drug: Trastuzumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse Events
CTCAE v.4.0
Measured: Up to 2 years
Maximum Tolerated Dose
CTCAE v.4.0
Measured: Up to 2 years
Secondary outcomes (1)
Response Rate
RECIST v.1.1
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Nov 2015 (estimated)
- Study start3 Nov 2015
- Primary completion5 Jan 2017
- Study completion31 Jul 2017
Why it stopped: toxicity
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Solid TumorStudies 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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Michelle Melisko
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Michelle Melisko, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02593708
- Sponsor's protocol ID
- 149517
- Status last verified
- Nov 2017
- First submitted
- 30 Oct 2015
- Last updated
- 17 Nov 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 17 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study to Evaluate the Safety of Neratinib in Combination With Paclitaxel, Trastuzumab and Pertuzumab in Women and Men With Advanced or Metastatic HER2+ Solid Tumors
- ClinicalTrials.gov ID
- NCT02593708
- Acronym / sponsor ID
- 149517
- Conditions
- Solid Tumor
- Keywords
- HER2+
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: toxicity
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Michelle MeliskoUniversity, hospital or other
- Study start
- 3 Nov 2015 (actual)
- Primary completion
- 5 Jan 2017 (actual)
- Study completion
- 31 Jul 2017 (actual)
- First posted
- 2 Nov 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Open label, non-randomized, dose escalation and expansion Phase Ia/b trial to evaluate the safety and tolerability of the combination of neratinib plus paclitaxel, trastuzumab and pertuzumab to determine the recommended Phase II/III dose of this combination.
Neratinib will be given once daily days 1-21 and should be taken orally with food. Paclitaxel and trastuzumab will be given IV on days 1, 8, and 15 out of 21 day cycles. Pertuzumab will be given IV every 3 weeks on day 1 out of 21-day cycles. Each cycle will be 21 days in duration.
Patients will continue on treatment until disease progression or intolerable toxicity.
Detailed description
Neratinib is a potent, irreversible, small molecule panErbB inhibitor of EGFR, HER2 and HER4 tyrosine kinases. Its activity prevents the autophosphorylation of HER2 and thus halts the downstream activation of this key proliferative pathway in tumors dependent on HER2 overexpression or EGFR activation. It has shown promising clinical activity in women with HER2+ stage 2 and 3 breast cancer in the neoadjuvant setting (I-SPY 2 TRIAL) and in women with stage 4 metastatic breast cancer, although evaluation in larger phase 3 trials is required to confirm these results.
The rationale for this study is to determine the feasibility of adding neratinib to a taxane based chemotherapy and the approved HER2 antagonists, trastuzumab and pertuzumab.
The study will evaluate the safety and tolerability and recommended dose of daily neratinib in combination with weekly paclitaxel, trastuzumab and tri-weekly pertuzumab in patients with HER2+ advanced or metastatic disease and, if successful, determine an optimal dose to move into phase II/III testing of this combination in the neoadjuvant setting.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Cohort 0 | Experimental | Drug: Neratinib, Drug: Paclitaxel, Drug: Pertuzumab, Drug: Trastuzumab1. Neratinib: 80 mg, daily, oral 2. Paclitaxel: 80 mg/m2, weekly, intravenously 3. Pertuzumab: 840 mg loading dose, 420 mg every 3 weeks, intravenously 4. Trastuzumab: 4 mg/kg loading dose, 2mg/kg every week, intravenously |
| Cohort 1 | Experimental | Drug: Neratinib, Drug: Paclitaxel, Drug: Pertuzumab, Drug: Trastuzumab1. Neratinib: 120 mg, daily, oral 2. Paclitaxel: 80 mg/m2, weekly, intravenously 3. Pertuzumab: 840 mg loading dose, 420 mg every 3 weeks, intravenously 4. Trastuzumab: 4 mg/kg loading dose, 2mg/kg every week, intravenously |
| Cohort 2 | Experimental | Drug: Neratinib, Drug: Paclitaxel, Drug: Pertuzumab, Drug: Trastuzumab1. Neratinib: 160 mg, daily, oral 2. Paclitaxel: 80 mg/m2, weekly, intravenously 3. Pertuzumab: 840 mg loading dose, 420 mg every 3 weeks, intravenously 4. Trastuzumab: 4 mg/kg loading dose, 2mg/kg every week, intravenously |
| Cohort 3 | Experimental | Drug: Neratinib, Drug: Paclitaxel, Drug: Pertuzumab, Drug: Trastuzumab1. Neratinib: 200 mg, daily, oral 2. Paclitaxel: 80 mg/m2, weekly, intravenously 3. Pertuzumab: 840 mg loading dose, 420 mg every 3 weeks, intravenously 4. Trastuzumab: 4 mg/kg loading dose, 2mg/kg every week, intravenously |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- Women and men 18 years or older with advanced solid tumor malignancy
- Ability to understand and voluntarily sign informed consent prior to undergoing any study-related assessments or procedures, as well as adhere to the study visit schedule and other protocol requirements.
- Local histologic or cytologic confirmation of HER2+ solid tumors by FISH amplification or IHC (3+)
- Patients must have received one prior approved therapy for metastatic disease and have not curable options
- For escalation: Documentation by established staging studies or clinical examination to have measurable or non-measurable metastatic disease per RECIST v1.1 criteria.
Key exclusion criteria (13 listed)
- Any significant medical condition, laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
- Any condition that confounds the ability to interpret data from the study.
- Patients must have recovered from side effects from prior cancer-directed therapy to grade 1 or less (unless deemed not clinically significant by study investigator).
- Symptomatic central nervous system metastases. Subjects with brain metastases that have been previously treated and are stable for 4 weeks are allowed.
- Persistent diarrhea or malabsorption ≥ NCI CTCAE grade 1, despite medical management, ulcerative colitis, inflammatory bowel disease, resection of the stomach or small bowel, or other disease or condition significantly affecting gastrointestinal function.
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 |
|---|---|---|
| Neratinib | Drug | Cohort 0, Cohort 1, Cohort 2, Cohort 3 |
| Paclitaxel | Drug | Cohort 0, Cohort 1, Cohort 2, Cohort 3 |
| Pertuzumab | Drug | Cohort 0, Cohort 1, Cohort 2, Cohort 3 |
| Trastuzumab | Drug | Cohort 0, Cohort 1, Cohort 2, Cohort 3 |
Primary outcome
Adverse Events
Time frame: Up to 2 years
CTCAE v.4.0
Maximum Tolerated Dose
Time frame: Up to 2 years
CTCAE v.4.0
1 secondary outcome
Response Rate
Time frame: Up to 2 years
Results and safety
The study was stopped early (reason given: toxicity). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Nov 2017.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Neratinib, Paclitaxel and Pertuzumab in people with Solid Tumor, run by Michelle Melisko at 1 site in United States.
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 25 inclusion and 13 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: stopped early, as of the sponsor's last update on 17 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: toxicity). Results are not available in the source record.
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?
Adverse Events (time frame: Up to 2 years). 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?
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 17 Nov 2017.