Metastatic Breast CancerPhase 1NCT02650752
Intermittent High-Dose Lapatinib in Tandem With Capecitabine for HER2 Overexpressed/Amplified Metastatic Breast Cancer With Central Nervous System (CNS) Metastases
A Phase 1 study testing Lapatinib in Tandem With Capecitabine in people with Metastatic Breast Cancer and Central Nervous System (CNS) Metastases, run by Memorial Sloan Kettering Cancer Center at 9 sites in United States.
Trial summary
The purpose of this study is to see if capecitabine can be taken safely with different doses of lapatinib in patients with HER-2 positive breast cancer involving brain (brain metastases) and/or in spinal fluid (leptomeningeal disease). Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Metastatic Breast Cancer, Central Nervous System (CNS) Metastases
- What is being tested?
- Lapatinib in Tandem With Capecitabine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 9 sitesUnited States
- Study dates
- 6 Jan 2016to 22 Jan 2021
- 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
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥18 years
- Histologically-confirmed metastatic adenocarcinoma of the breast with either invasive primary tumor or metastatic tissue confirmation of HER2+ status as defined by immunohistochemistry (IHC) with score of 3+, or, if 2+ with confirmatory fluorescence in situ hybridization (FISH) ratio of ≥ 2.0
- Received prior trastuzumab or chemotherapy for metastatic breast cancer except if patient has CNS as only site of metastatic disease.
- Radiologic evidence of new and/or progressive parenchymal brain metastasis, spinal cord metastases ( intramedullary) or leptomeningeal disease (LMD) by magnetic resonance (MR) imaging of the brain and/or spine, or CSF cytology evidence of new LMD.
- Life expectancy of >12 weeks.
- ECOG Performance of 0 to 2
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- Non-escalating corticosteroid dose (not exceeding more than 16 mg daily of dexamethasone oral) for ≥ 5 days.
- Prior therapy:
- No limit to prior therapies with last anti-cancer treatment ≥ 2 weeks from initiation of protocol-based therapy provided all toxicities (other than alopecia) have resolved to ≤Grade 1 or baseline. For lapatinib and IV trastuzumab and/or pertuzumab, no washout is required.
- Patients with prior whole brain radiation therapy (WBRT) or stereotactic radiosurgery (SRS) are eligible, provided that there are new lesions not previously treated by SRS and ≥4 weeks have passed since radiation
- Patients with prior cranial surgery are eligible, provided that there is evidence of residual disease and/or progression of disease and ≥4 weeks have passed since surgery.
- Prior hormonal therapy for locally advanced or metastatic disease is allowed and can be continued. If everolimus is used in a combination with hormonal therapy, then, everolimus must be discontinued but hormonal therapy can be continued.
- Continuation of intravenous (IV) trastuzumab is allowed for those patients already on IV trastuzumab therapy. Patients previously treated with intrathecal (IT) trastuzumab are allowed if there is evidence of progression as determined by treating physician and last dose administered is ≥ 4 weeks.
- Prior capecitabine therapy is allowed, provided ≥6 months have passed since the last dose of capecitabine.
- Cardiac ejection fraction at or above the lower limit of normal as measured by multigated radionuclide angiography (MUGA) scans or echocardiogram documented ≤ 3 months prior to registration.
- Adequate bone marrow, liver, and renal function as assessed by the following:
- Granulocyte count ≥ 1,000/μL for lapatinib and > 1,500/uL for capecitabine , platelet count ≥ 100,000/μL, and hemoglobin ≥ 8 g/dL
- Serum bilirubin ≤ 1.5 mg/dL; AST, ALT, and alkaline phosphatase ≤ 2.5 × ULN except for: Patients with hepatic metastases: ALT and AST ≤ 5 × ULN; patients with hepatic and/or bone metastases: alkaline phosphatase ≤ 5 × ULN and patients with Gilbert's disease: serum bilirubin < 5 mg/dL
- Serum creatinine ≤ 1.5 mg/dL or creatinine clearance of ≥ 60 mL/min based on a 24-hour urine collection
- Women of childbearing potential must have a negative serum pregnancy test performed within 14 days prior to enrollment. Women of childbearing potential and men must agree to use adequate contraception prior to enrollment and for the duration of study participation.
- Patients must be able to swallow and retain oral medication.
Who cannot join
- Contraindications or history of allergic reaction to lapatinib or to capecitabine, known dihydropyrimidine dehydrogenase deficiency, or known hypersensitivity of 5-fluorouracil.
- Craniotomy or any other major surgery, open biopsy, or significant traumatic injury within 4 weeks of enrollment.
- Serious, non-healing wound, infection, ulcer, bone fracture, or uncontrolled seizures
- Significant gastrointestinal disorder with diarrhea as a major symptom (example Crohn's disease, ulcerative colitis) or Grade ≥ 2 diarrhea of any etiology at baseline. Active hepatobiliary disease with the exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases, or stable chronic liver disease as determined by investigator's assessment.
- Significant medical co-morbidities as described below:
- Cardiac disease:
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- Congestive heart failure >class II New York Heart Association (NYHA) or
- Unstable angina (anginal symptoms at rest), or new-onset angina (begun within the last 3 months), or myocardial infarction within the 6 months prior to enrollment, or
- Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
- Known history of QTc prolongation or Torsades de Pointes
- Grade 3 hypertension (SBP ≥ 160 mm Hg and/or DBP ≥ 100 mm Hg despite maximal medical therapy)
- Thrombotic, embolic, venous, or arterial events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months.
- Known human immunodeficiency virus (HIV) infection or chronic hepatitis B or C
- Previous or concurrent cancer that is distinct in primary site or histology from breast cancer within 5 years prior to enrollment EXCEPT cervical cancer in situ, treated non-melanoma skin cancers, superficial bladder tumors [Ta and Tis].
- Concurrent medication:
- Rivaroxaban and vitamin-K antagonists (e.g., warfarin), but enoxaparin is allowed.
- No concurrent use of strong CYP3A4 inhibitor (e.g., ketoconazole, voriconazole, grapefruit) or inducers (e.g., phenytoin, carbamazepine, phenobarbital, St. John's Wort [Hypericum perforatum], dexamethasone at a dose of greater than 16 mg daily, or rifampin [rifampicin], and/or rifabutin). 2 week washout period before enrollment required if any of strong inducer or inhibitors used (except for dexamethasone, dose needs to be 16mg or less daily). (Appendix H)
- Use of concurrent cytochrome P450 enzyme-inducing anti-epileptic drugs (such as phenytoin, carbamazepine, or phenobarbital) is not allowed. (Anti-epileptic levetiracetam is allowed).
- Concurrent anti-cancer therapy (chemotherapy, hormonal therapy, radiation therapy, surgery, immunotherapy, tumor embolization, or biologic therapy including pertuzumab, but except IV trastuzumab or hormonal therapy, if patient is already being treated with either of the two agents.)
- Use of any investigational drug within 28 days or 5 half-lives, whichever is longer, preceding enrollment.
- Women who are pregnant or breast-feeding.
- Inability to comply with protocol and /or not willing or not available for follow-up assessments or any condition which in the investigator's opinion makes the patient unsuitable for the study participation.
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
United States9 sites
University of Michigan Health System
Ann Arbor, Michigan, 48109
Memoral Sloan Kettering Cancer Center
Basking Ridge, New Jersey
Memorial Sloan Kettering Cancer Center @ Suffolk
Commack, New York, 11725
Memorial Sloan Kettering Westchester
Harrison, New York, 10604
Queens Cancer Center of Queens Hospital
Jamaica, New York, 11432
Memorial Sloan Kettering Monmouth
Middletown, New Jersey, 07748
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Memorial Sloan Kettering at Mercy Medical Center
Rockville Centre, New York
Memorial Sloan Kettering Nassau
Uniondale, New York, 11553
About this study
Official title: Phase I Study of Intermittent High-Dose Lapatinib in Tandem With Capecitabine for HER2 Overexpressed/Amplified Metastatic Breast Cancer With Central Nervous System (CNS) Metastases
The purpose of this study is to see if capecitabine can be taken safely with different doses of lapatinib in patients with HER-2 positive breast cancer involving brain (brain metastases) and/or in spinal fluid (leptomeningeal disease).
- Being tested
- Lapatinib in Tandem With Capecitabine
- Keywords
- Lapatinib, Capecitabine, HER2, 15-278
- Medical subject headings
- Breast Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lapatinib in Tandem With CapecitabineDrug
| Study group | Role | What they receive |
|---|---|---|
| Lapatinib in Tandem With Capecitabine | Experimental | A minimum of one patient at each dose level will be enrolled. Patients will receive a 4 week treatment cycle consisting of lapatinib 3 day on/11 day off in tandem with capecitabine 7 day on/7 day off with lapatinib. Both drugs will be administered orally as outpatient. Safety, toxicity, and DLT will be assessed weekly during the cycle 1 (first 4 weeks). Each patient will be monitored during cycle 1 prior to enrolling the next patient to the next higher dose level. Dose escalation will take place if no DLT or less than two occurrences of grade 2 toxicity (except those listed below) is observed within a given patient. In the event that a second instance of separate grade 2 toxicity (except those listed below) is noted, the cohort will be expanded to 3 patients at the same dose level and the study will revert to the standard 3+3 design with 3 patients per cohort. There will be no intra-patient dose escalation. Receives: Drug: Lapatinib in Tandem With Capecitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
maximum tolerated dose (MTD)
During the standard 3+3, the probability that dose escalation will occur at any stage during MTD determination is a function of the underlying DLT rate at the current dose level. This probability can be calculated as the sum of the binomial probabilities of the following two outcomes that would permit escalation to occur:
- No DLT observed in the first three patients.
- One DLT is observed in the first three patients followed by no DLT observed in three additional patients at the same dose level.
Measured: first 28-day cycle
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jan 2016 (estimated)
- Study start6 Jan 2016
- Primary completion22 Jan 2021
- Study completion22 Jan 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metastatic Breast CancerStudies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering 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
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Queens Cancer Center of Queens Hospital, University of Michigan
- Responsible party
- Sponsor
- Investigators
- Andrew Seidman, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02650752
- Sponsor's protocol ID
- 15-278
- Status last verified
- Jan 2021
- First submitted
- 6 Jan 2016
- Last updated
- 26 Jan 2021
- Results posted
- No
Publications
Morikawa A, de Stanchina E, Pentsova E, Kemeny MM, Li BT, Tang K, Patil S, Fleisher M, Van Poznak C, Norton L, Seidman AD. Phase I Study of Intermittent High-Dose Lapatinib Alternating with Capecitabine for HER2-Positive Breast Cancer Patients with Central Nervous System Metastases. Clin Cancer Res. 2019 Jul 1;25(13):3784-3792. doi: 10.1158/1078-0432.CCR-18-3502. Epub 2019 Apr 15.
PubMed 30988080
Study at a glance
From the registry record, last updated by the sponsor on 26 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of Intermittent High-Dose Lapatinib in Tandem With Capecitabine for HER2 Overexpressed/Amplified Metastatic Breast Cancer With Central Nervous System (CNS) Metastases
- ClinicalTrials.gov ID
- NCT02650752
- Acronym / sponsor ID
- 15-278
- Keywords
- Lapatinib, Capecitabine, HER2, 15-278
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Collaborators
- Queens Cancer Center of Queens Hospital, University of Michigan
- Study start
- 6 Jan 2016
- Primary completion
- 22 Jan 2021 (actual)
- Study completion
- 22 Jan 2021 (actual)
- First posted
- 8 Jan 2016 (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.
The purpose of this study is to see if capecitabine can be taken safely with different doses of lapatinib in patients with HER-2 positive breast cancer involving brain (brain metastases) and/or in spinal fluid (leptomeningeal disease).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Lapatinib in Tandem With Capecitabine | Experimental | Drug: Lapatinib in Tandem With CapecitabineA minimum of one patient at each dose level will be enrolled. Patients will receive a 4 week treatment cycle consisting of lapatinib 3 day on/11 day off in tandem with capecitabine 7 day on/7 day off with lapatinib. Both drugs will be administered orally as outpatient. Safety, toxicity, and DLT will be assessed weekly during the cycle 1 (first 4 weeks). Each patient will be monitored during cycle 1 prior to enrolling the next patient to the next higher dose level. Dose escalation will take place if no DLT or less than two occurrences of grade 2 toxicity (except those listed below) is observed within a given patient. In the event that a second instance of separate grade 2 toxicity (except those listed below) is noted, the cohort will be expanded to 3 patients at the same dose level and the study will revert to the standard 3+3 design with 3 patients per cohort. There will be no intra-patient dose escalation. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Age ≥18 years
- Histologically-confirmed metastatic adenocarcinoma of the breast with either invasive primary tumor or metastatic tissue confirmation of HER2+ status as defined by immunohistochemistry (IHC) with score of 3+, or, if 2+ with confirmatory fluorescence in situ hybridization (FISH) ratio of ≥ 2.0
- Received prior trastuzumab or chemotherapy for metastatic breast cancer except if patient has CNS as only site of metastatic disease.
- Radiologic evidence of new and/or progressive parenchymal brain metastasis, spinal cord metastases ( intramedullary) or leptomeningeal disease (LMD) by magnetic resonance (MR) imaging of the brain and/or spine, or CSF cytology evidence of new LMD.
- Life expectancy of >12 weeks.
Key exclusion criteria (22 listed)
- Contraindications or history of allergic reaction to lapatinib or to capecitabine, known dihydropyrimidine dehydrogenase deficiency, or known hypersensitivity of 5-fluorouracil.
- Craniotomy or any other major surgery, open biopsy, or significant traumatic injury within 4 weeks of enrollment.
- Serious, non-healing wound, infection, ulcer, bone fracture, or uncontrolled seizures
- Significant gastrointestinal disorder with diarrhea as a major symptom (example Crohn's disease, ulcerative colitis) or Grade ≥ 2 diarrhea of any etiology at baseline. Active hepatobiliary disease with the exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases, or stable chronic liver disease as determined by investigator's assessment.
- Significant medical co-morbidities as described below:
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 |
|---|---|---|
| Lapatinib in Tandem With Capecitabine | Drug | Lapatinib in Tandem With Capecitabine |
Primary outcome
maximum tolerated dose (MTD)
Time frame: first 28-day cycle
During the standard 3+3, the probability that dose escalation will occur at any stage during MTD determination is a function of the underlying DLT rate at the current dose level. This probability can be calculated as the sum of the binomial probabilities of the following two outcomes that would permit escalation to occur: 1. No DLT observed in the first three patients. 2. One DLT is observed in the first three patients followed by no DLT observed in three additional patients at the same dose level.
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 26 Jan 2021.
- Derived from this study: PubMed 30988080Morikawa A, de Stanchina E, Pentsova E, Kemeny MM, Li BT, Tang K, Patil S, Fleisher M, Van Poznak C, Norton L, Seidman AD. Phase I Study of Intermittent High-Dose Lapatinib Alternating with Capecitabine for HER2-Positive Breast Cancer Patients with Central Nervous System Metastases. Clin Cancer Res. 2019 Jul 1;25(13):3784-3792. doi: 10.1158/1078-0432.CCR-18-3502. Epub 2019 Apr 15.
- Memorial Sloan Kettering Cancer CenterLink provided by the sponsor.
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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.
Andrew Seidman, MD principal investigator
Memorial Sloan Kettering Cancer Center
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Lapatinib in Tandem With Capecitabine in people with Metastatic Breast Cancer and Central Nervous System (CNS) Metastases, run by Memorial Sloan Kettering Cancer Center at 9 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 21 inclusion and 22 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 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 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?
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 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?
maximum tolerated dose (MTD) (time frame: first 28-day cycle). 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 NCT02650752, 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 Jan 2021.