Breast NeoplasmsEarly Phase 1NCT01875666
Defining the HER2 Positive (+) Breast Cancer Kinome Response to Trastuzumab, Pertuzumab, Combination Trastuzumab +Pertuzumab, or Combination Trastuzumab + Lapatinib
A Early Phase 1 study testing Trastuzumab, pertuzumab and lapatinib in people with Breast Neoplasms, run by UNC Lineberger Comprehensive Cancer Center at 5 sites in United States.
Trial summary
Kinases are a group of proteins that are important in how cancer cells grow. HER2 is a kind of kinase. This study looks at a new approach to identifying kinases, which may help target therapy more precisely. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Neoplasms
- What is being tested?
- Trastuzumab, pertuzumab and lapatinib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 5 sitesUnited States
- Study dates
- 5 Aug 2013to 19 Dec 2016
- Phase
- Early 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
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed, written informed consent
- Age >/= 18 years
- Histologically confirmed HER2+ breast cancer: IHC 3+ or fluorescence in situ hybridization [FISH] amplified; by clinical assay on either primary or metastatic tumor
- Stage I-IV disease
- For patients with Stage I-IIIc disease:
- Scheduled for lumpectomy or mastectomy
Show all 23Show fewer
- No prior or current therapy for breast cancer
- Not considered a candidate for therapeutic neoadjuvant treatment
- For patients with Stage IV disease:
- Scheduled for surgical resection of oligometastatic disease
- Previously untreated for breast cancer
- Normal relevant end organ function as defined by the following:
- ANC>1500 cells/mL
- Platelets > 100,000 cells/mL
- Hemoglobin > 10 g/dL
- Total bilirubin ≤ 1.5 x ULN (unless known Gilbert's syndrome)
- AST and ALT ≤ 2.5 X ULN
- Creatinine ≤ 1.5 X ULN OR Calculated creatinine clearance ≥50 mL/min OR 24-hour urine creatinine clearance ≥50 mL/min
- Left Ventricular Ejection Fraction ≥ 50% by ECHO (preferred) or MUGA
- For women of childbearing potential, agreement to use an effective form of contraception (patient and/or partner, e.g., surgical sterilization, a reliable barrier method, birth control pills, or contraceptive hormone implants) and to continue its use for the duration of the study treatment, and for a minimum of 6 months following trastuzumab and/or pertuzumab administration.
- Sufficient fresh or frozen tissue remaining from pre-treatment core biopsy/ incisional biopsy or willing to undergo biopsy (at UNC via LCCC9819) for research purposes only (approximately 10mg or one core's worth of tissue needed)
- Surgeon and medical oncologist agree one week window trial is appropriate/safe for the patient and that surgery appointment can accommodate treatment schedule as outlined in the study schema (section 4.1).
- UNC patients must co-enroll into LCCC9819 for collection of tissue samples
Who cannot join
- Pregnant or lactating female
- Prior radiation therapy to the target lesion
- Use of any investigational drug within 28 days or five half-lives, whichever is shorter, prior to the first dose of study medication; a minimum of 10 days between termination of the investigational drug and treatment with study medication is required
- Any major radiotherapy, tumor-directed systemic or immunotherapy within the last 4 weeks for any indication
- Candidate for therapeutic neoadjuvant treatment
- Active infection
Show all 19Show fewer
- Evidence of severe or uncontrolled systemic diseases (e.g., unstable or uncompensated respiratory, hepatic, renal, or cardiac disease)
- Required administration of concomitant moderate or strong inhibitors or inducers of CYP3A4 for 14 days prior to the first dose of study drug prior amiodarone for up to 6 months prior to day 1 of study treatment
- Inability to take oral medications e.g., impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral medications (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
- History or evidence of cardiovascular risk including any of the following:
- Current uncontrolled hypertension (systolic >150 mm Hg and/or diastolic >100 mmHg) or unstable angina
- History of serious cardiac arrhythmia requiring treatment (exceptions: atrial fibrillation, paroxysmal supraventricular tachycardia)
- History of myocardial infarction within 6 months of day 1 of dosing
- History of CHF of New York Heart Association (NYHA) criteria
- Known human immunodeficiency virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection (with the exception of chronic or cleared HBV and HCV infection which will be allowed)
- Have acute or currently active/requiring anti-viral therapy hepatic or biliary disease (with the exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment).
- Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study drugs
- Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol
- Any other concurrent condition that in the investigator's opinion would jeopardize compliance with the protocol
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
University of Alabama at Birmingham
Birmingham, Alabama, 35294
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
Lineberger Comprehensive Cancer Center, UNC
Chapel Hill, North Carolina, 27599
MD Anderson
Houston, Texas, 77030-4008
IU Simon Cancer Center
Indianapolis, Indiana, 46202
About this study
Kinases are a group of proteins that are important in how cancer cells grow. HER2 is a kind of kinase. This study looks at a new approach to identifying kinases, which may help target therapy more precisely.
LCCC1214 is a randomized, multiarm, multicenter, open-label window trial designed to explore the kinome response in Stage I-IV HER2 positive (HER2+) breast cancer patients scheduled to undergo definitive surgery (either lumpectomy, mastectomy or surgical resection of oligometastatic disease). Patients will initiate dosing with either a single HER2-directed agent or a combination of two HER2-directed agents, one week prior to surgery. Forty patients will be randomized to one of four study groups:
Read more
- single dose trastuzumab; B) single dose pertuzumab; C) combination single dose trastuzumab plus single dose pertuzumab; or D) combination single dose trastuzumab plus lapatinib daily for 7 days.
Pre- and post- dosing tissue will be analyzed for kinome response and resistant signatures. The initiation of study drug will be defined by the surgical schedule; there will be no delays in standard treatment for the purposes of this study.
Read the detailed description
Until recently, our understanding of the kinome has been limited to just 5-10% of the genome-encoded kinases. This limited knowledge prevents a thorough understanding of resistance mechanisms, and precludes individualizing HER2-targeted therapy in HER2+ disease. Fortunately, we have now developed a chemical proteomics approach to define comprehensive kinome activity in cells and tumors (MIB/MS).[1]
We hypothesize that our proteomics approach can be used to characterize the heterogeneity of the kinome activation profiles in HER2+ breast cancer and permit us to identify if adaptive response to HER2 inhibition differs depending on the anti-HER2 drug mechanism of action. This will allow rational prediction of new combinatorial therapies in future clinical trials.
To explore kinome activation in this population, we propose a window trial in stage I-IV HER2+ patients scheduled to undergo definitive surgery (either lumpectomy, mastectomy or surgical resection of oligometastatic disease). Enrolled patients will be randomized to one of four treatment arms; A) single dose trastuzumab; B) single dose pertuzumab; C) combination trastuzumab + pertuzumab for one dose each; or D) combination single dose trastuzumab plus lapatinib daily for one week.
Dosing in each arm will be initiated 7 days prior to surgery, with pre- and post-dosing tissue samples analyzed for kinome response and resistant signatures. To ensure adequate levels of trastuzumab and pertuzumab at the time of surgery, a loading dose of each agent (8 mg/kg IV for trastuzumab, and 840 mg IV fixed dose for pertuzumab) were chosen. The dose of lapatinib was based on prior studies of lapatinib administered in combination with trastuzumab. Given the varied pharmacokinetic profiles of the three agents and limited dosing, we expect exposure levels of the agents to be different relative to respective steady state levels. Therefore qualitative rather than quantitative measures will be key.
- Conditions
- Breast Neoplasms
- Being tested
- Trastuzumab, pertuzumab, lapatinib
- Keywords
- breast cancer, Kinome, HER two positive
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TrastuzumabDrug
Also called Herceptin
8 mg/kg IV, single dose
pertuzumabDrug
Also called Perjeta
840 mg IV single dose
lapatinibDrug
Also called Tykerb
1000 mg daily for 7 days
| Study group | Role | What they receive |
|---|---|---|
| Trastuzumab | Active comparator | single dose intravenous infusion administration of trastuzumab (8 mg/kg) Receives: Drug: Trastuzumab |
| pertuzumab | Active comparator | single dose infusion of pertuzumab (840 mg) Receives: Drug: pertuzumab |
| trastuzumab plus pertuzumab | Active comparator | single dose infusion of combination trastuzumab (8 mg/kg) plus pertuzumab (840 mg) Receives: Drug: Trastuzumab; Drug: pertuzumab |
| trastuzumab plus lapatinib | Active comparator | combination of single dose infusion of trastuzumab (8 mg/kg) plus oral lapatinib (1000 mg daily for 7 days) Receives: Drug: Trastuzumab; Drug: lapatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
difference in kinome activation pre and post treatment
To identify differential kinome activation before and after treatment with a single dose of trastuzumab, pertuzumab, the combination of trastuzumab + pertuzumab, or the combination of single dose trastuzumab+once daily lapatinib for 7 days, in patients with HER2+ breast cancer
Measured: 7-10 days prior to surgery and at surgery
Secondary outcomes (1)
predictability in kinome activation
to see if different kinase activation patterns can predict the optimal HER2 inhibition for treatment.
Measured: kinoming analysis of tissue will be done after subject participation, which will last from 7-10 days prior to surgery.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jun 2013 (estimated)
- Study start5 Aug 2013
- Primary completion19 Dec 2016
- Study completion19 Dec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast NeoplasmsStudies of the same condition, open and under way.
- More trials run by UNC Lineberger Comprehensive Cancer CenterThe sponsor's other registered studies.
- 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
- Early Phase 1
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- UNC Lineberger Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc., Susan G. Komen Breast Cancer Foundation, GlaxoSmithKline
- Responsible party
- Sponsor
- Investigators
- Lisa A Carey, MD, Principal investigator, University of North Carolina, Chapel Hill
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01875666
- Sponsor's protocol ID
- LCCC 1214
- Status last verified
- Jul 2020
- First submitted
- 4 Jun 2013
- Last updated
- 4 Sep 2020
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 4 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Defining the HER2 Positive (+) Breast Cancer Kinome Response to Trastuzumab, Pertuzumab, Combination Trastuzumab +Pertuzumab, or Combination Trastuzumab + Lapatinib
- ClinicalTrials.gov ID
- NCT01875666
- Acronym / sponsor ID
- LCCC 1214
- Conditions
- Breast Neoplasms
- Keywords
- breast cancer, Kinome, HER two positive
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- UNC Lineberger Comprehensive Cancer CenterUniversity, hospital or other
- Collaborators
- Genentech, Inc., Susan G. Komen Breast Cancer Foundation, GlaxoSmithKline
- Study start
- 5 Aug 2013 (actual)
- Primary completion
- 19 Dec 2016 (actual)
- Study completion
- 19 Dec 2016 (actual)
- First posted
- 12 Jun 2013 (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.
Kinases are a group of proteins that are important in how cancer cells grow. HER2 is a kind of kinase. This study looks at a new approach to identifying kinases, which may help target therapy more precisely.
LCCC1214 is a randomized, multiarm, multicenter, open-label window trial designed to explore the kinome response in Stage I-IV HER2 positive (HER2+) breast cancer patients scheduled to undergo definitive surgery (either lumpectomy, mastectomy or surgical resection of oligometastatic disease). Patients will initiate dosing with either a single HER2-directed agent or a combination of two HER2-directed agents, one week prior to surgery. Forty patients will be randomized to one of four study groups:
- single dose trastuzumab; B) single dose pertuzumab; C) combination single dose trastuzumab plus single dose pertuzumab; or D) combination single dose trastuzumab plus lapatinib daily for 7 days.
Pre- and post- dosing tissue will be analyzed for kinome response and resistant signatures. The initiation of study drug will be defined by the surgical schedule; there will be no delays in standard treatment for the purposes of this study.
Detailed description
Until recently, our understanding of the kinome has been limited to just 5-10% of the genome-encoded kinases. This limited knowledge prevents a thorough understanding of resistance mechanisms, and precludes individualizing HER2-targeted therapy in HER2+ disease. Fortunately, we have now developed a chemical proteomics approach to define comprehensive kinome activity in cells and tumors (MIB/MS).[1]
We hypothesize that our proteomics approach can be used to characterize the heterogeneity of the kinome activation profiles in HER2+ breast cancer and permit us to identify if adaptive response to HER2 inhibition differs depending on the anti-HER2 drug mechanism of action. This will allow rational prediction of new combinatorial therapies in future clinical trials.
To explore kinome activation in this population, we propose a window trial in stage I-IV HER2+ patients scheduled to undergo definitive surgery (either lumpectomy, mastectomy or surgical resection of oligometastatic disease). Enrolled patients will be randomized to one of four treatment arms; A) single dose trastuzumab; B) single dose pertuzumab; C) combination trastuzumab + pertuzumab for one dose each; or D) combination single dose trastuzumab plus lapatinib daily for one week.
Dosing in each arm will be initiated 7 days prior to surgery, with pre- and post-dosing tissue samples analyzed for kinome response and resistant signatures. To ensure adequate levels of trastuzumab and pertuzumab at the time of surgery, a loading dose of each agent (8 mg/kg IV for trastuzumab, and 840 mg IV fixed dose for pertuzumab) were chosen. The dose of lapatinib was based on prior studies of lapatinib administered in combination with trastuzumab. Given the varied pharmacokinetic profiles of the three agents and limited dosing, we expect exposure levels of the agents to be different relative to respective steady state levels. Therefore qualitative rather than quantitative measures will be key.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Trastuzumab | Active comparator | Drug: Trastuzumabsingle dose intravenous infusion administration of trastuzumab (8 mg/kg) |
| pertuzumab | Active comparator | Drug: pertuzumabsingle dose infusion of pertuzumab (840 mg) |
| trastuzumab plus pertuzumab | Active comparator | Drug: Trastuzumab, Drug: pertuzumabsingle dose infusion of combination trastuzumab (8 mg/kg) plus pertuzumab (840 mg) |
| trastuzumab plus lapatinib | Active comparator | Drug: Trastuzumab, Drug: lapatinibcombination of single dose infusion of trastuzumab (8 mg/kg) plus oral lapatinib (1000 mg daily for 7 days) |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- Signed, written informed consent
- Age >/= 18 years
- Histologically confirmed HER2+ breast cancer: IHC 3+ or fluorescence in situ hybridization [FISH] amplified; by clinical assay on either primary or metastatic tumor
- Stage I-IV disease
- Normal relevant end organ function as defined by the following:
Key exclusion criteria (19 listed)
- Pregnant or lactating female
- Prior radiation therapy to the target lesion
- Use of any investigational drug within 28 days or five half-lives, whichever is shorter, prior to the first dose of study medication; a minimum of 10 days between termination of the investigational drug and treatment with study medication is required
- Any major radiotherapy, tumor-directed systemic or immunotherapy within the last 4 weeks for any indication
- Candidate for therapeutic neoadjuvant treatment
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 |
|---|---|---|
| TrastuzumabAlso: Herceptin8 mg/kg IV, single dose | Drug | Trastuzumab, trastuzumab plus lapatinib, trastuzumab plus pertuzumab |
| pertuzumabAlso: Perjeta840 mg IV single dose | Drug | pertuzumab, trastuzumab plus pertuzumab |
| lapatinibAlso: Tykerb1000 mg daily for 7 days | Drug | trastuzumab plus lapatinib |
Primary outcome
difference in kinome activation pre and post treatment
Time frame: 7-10 days prior to surgery and at surgery
To identify differential kinome activation before and after treatment with a single dose of trastuzumab, pertuzumab, the combination of trastuzumab + pertuzumab, or the combination of single dose trastuzumab+once daily lapatinib for 7 days, in patients with HER2+ breast cancer
1 secondary outcome
predictability in kinome activation
Time frame: kinoming analysis of tissue will be done after subject participation, which will last from 7-10 days prior to surgery.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Sep 2020.
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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.
Lisa A Carey, MD principal investigator
University of North Carolina, Chapel Hill
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Trastuzumab, pertuzumab and lapatinib in people with Breast Neoplasms, run by UNC Lineberger Comprehensive Cancer Center at 5 sites 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 23 inclusion and 19 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 4 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
difference in kinome activation pre and post treatment (time frame: 7-10 days prior to surgery and at surgery). 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 4 Sep 2020.