Breast CancerPhase 2NCT00721630
Novel Capecitabine Dosing Schedule in Combination With Lapatinib, Based on the Norton-Simon Mathematical Method in Patients With HER2 Overexpressed/Amplified, Trastuzumab (Herceptin) -Refractory, Metastatic Breast Cancer
A Phase 2 study testing capecitabine, lapatinib in people with Breast Cancer, run by Memorial Sloan Kettering Cancer Center at 5 sites in United States.
Trial summary
HER2 is a protein that sits on the surface of breast cancer cells in some people. Because you are one of these people, your breast cancer is called "HER2-positive." The HER2 protein is involved in the growth of your breast cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer
- What is being tested?
- capecitabine, lapatinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 5 sitesUnited States
- Study dates
- Jul 2008to Jul 2016
- Phase
- Phase 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
- Patients with a diagnosis of invasive adenocarcinoma of the breast confirmed by histology or cytology at MSKCC.
- Clinical evidence of metastatic breast cancer.
- HER2 overexpression and/or amplification as determined by immunohistochemistry (3+) or FISH (≥2.0).
- Progressive disease following treatment with trastuzumab for metastatic breast cancer or as adjuvant therapy (either single-agent or combination therapy)
- Prior therapy inclusion:
- No more than two prior chemotherapy regimens allowed for advanced stage disease
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- No prior fluoropyrimidine in the metastatic setting. Adjuvant fluoropyrimidine is permitted if >6 months prior to treatment on study.
- No restriction for prior hormonal therapy. No concurrent use of endocrine therapy is permitted.
- No more than 450mg/m2 cumulative dose of prior doxorubicin
- At least 3 weeks since prior chemotherapy or radiation therapy
- Age ≥ or = to 18. Because no dosing or adverse event data are currently available on the use of lapatinib in patients <18 years of age, children are excluded from this study.
- Patients must be willing to discontinue sex hormonal therapy e.g., birth control pills, ovarian hormonal replacement therapy, etc., prior to enrollment. Women of childbearing potential must be willing to consent to using effective contraception while on treatment and for a reasonable period thereafter.
- Negative HCG pregnancy test for premenopausal women of reproductive capacity and for women less than 12 months after the menopause.
- Asymptomatic, central nervous system metastases are permitted if patients remain clinically stable after discontinuation of corticosteroids and anticonvulsants.
- ECOG performance status < or = to 2
- Life expectancy of greater than 12 weeks
- Patients must have normal organ and marrow function as defined below:
- leukocytes ≥ or = to 3,000/μL
- absolute neutrophil count ≥ or = 1,500/μL
- platelets ≥ or = 100,000/μL
- total bilirubin within normal institutional limits AST (SGOT)/ALT(SGPT) ≤ or = 2.5x institutional upper limit of normal serum creatinine within normal institutional limits
- Cardiac ejection fraction at or above the lower limit of normal of 50% as measured by multigated radionuclide angiography (MUGA) scan. If LVEF is greater than 70%, and ECHO should be performed as well. Baseline and on treatment scans should be performed using the same modality and preferably at the same institution.
- Ability to understand and the willingness to sign a written informed. consent document.
- Able to swallow and retain oral medication.
Who cannot join
- Patients may not be receiving any concurrent anticancer therapy or investigational agents with the intention of treating breast cancer.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to lapatinib or capecitabine.
- Known DPD deficiency.
- Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction within 6 months of study entry, uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant women are excluded from this study because lapatinib is member of the 4- anilinoquinazoline class of kinase inhibitors with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with lapatinib, breastfeeding should be discontinued if the mother is treated with lapatinib.
- HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with lapatinib. Appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated.
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- Patients with GI tract disease resulting in an inability to take oral medication, malabsorption syndrome, a requirement for IV alimentation, prior surgical procedures affecting absorption,uncontrolled inflammatory GI disease (e.g., Crohn's, ulcerative colitis).
- Concomitant requirement for medication classified as CYP3A4 inducers or inhibitors:
- Medications that inhibit or induce CYP3A4 are prohibited. Eligibility of patients receiving medications or substances known to affect, or with the potential to affect the activity or pharmacokinetics of lapatinib will be determined following review of their use by the Principal Investigator.
- Renal function as measured by creatinine clearance < 30ml/min
- Patients are permitted to participate in other non-therapeutic clinical trials while receiving treatment on this study (ie, experimental imaging, minor procedures necessary for tissue acquisition on study)
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Memorial Sloan-Kettering at Basking Ridge
Basking Ridge, New Jersey, 07920
Memorial Sloan-Kettering Cancer Center at Commack
Commack, New York, 11725
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065
Memorial Sloan-Kettering Cancer Center at Mercy Medical Center
Rockville Centre, New York, 11570
Memorial Sloan-Kettering Cancer Center at Phelps Memorial Hospital Center
Sleepy Hollow, New York, 10591
About this study
Official title: Phase II Study of a Novel Capecitabine Dosing Schedule in Combination With Lapatinib, Based on the Norton-Simon Mathematical Method in Patients With HER2 Overexpressed/Amplified, Trastuzumab (Herceptin) -Refractory, Metastatic Breast Cancer
HER2 is a protein that sits on the surface of breast cancer cells in some people. Because you are one of these people, your breast cancer is called "HER2-positive." The HER2 protein is involved in the growth of your breast cancer. Certain drugs can interfere with the ability of the HER2 protein to cause breast cancer growth. Trastuzumab is one of these drugs. You must have already received trastuzumab as treatment for your breast cancer to be considered for this study.
Other drugs are being studied in women with HER2-positive breast cancer. Lapatinib (Tykerb™) blocks signals that stimulate HER2-positive breast cancers to grow. The FDA approved lapatinib for use with capecitabine (Xeloda™) in patients who have metastatic breast cancer that has grown or spread after treatment with trastuzumab.
Capecitabine was approved by the FDA in 1998 for treating metastatic breast cancer. Capecitabine is a pill that blocks the way cancer cells multiply and grow. Usually, this medicine is taken twice a day for fourteen days. Then, patients do not take the pill for seven days. With this schedule and dose, some patients have had side effects that interfered with their comfort. We have used mathematical models to recommend a new schedule of capecitabine. In animals, 7 days of treatment with capecitabine followed by a 7-day break was safer and more active against breast cancer. The purpose of this study is to find out what effect (both good and bad) capecitabine has on you and your breast cancer when given in this new schedule and combined with lapatinib.
- Conditions
- Breast Cancer
- Being tested
- capecitabine, lapatinib
- Keywords
- CAPECITABINE, LAPATINIB
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
capecitabine, lapatinibDrug
Capecitabine 2,000mg twice daily for 7 days followed by a 7-day rest in combination with lapatinib 1,250mg orally daily. Cycle length is 28 days (+/- 2 days).Toxicity assessment will occur q2 weeks for the first 4 weeks, then q4 weeks(+/- 2 days). Radiographic response assessment will take place q12 weeks (+/- 1 week). LVEF assessment will be repeated q12 weeks (+/- 1 week).
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | The regimen consists of capecitabine 2,000mg twice daily for 7 days followed by a 7-day rest in combination with lapatinib 1,250mg orally daily. Receives: Drug: capecitabine, lapatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Estimate Efficacy of Capecitabine 7/7 in Combination With Lapatinib in Patients With HER2 Overexpressed/Amplified, Trastuzumab-refractory, Metastatic Breast Cancer as Determined by Overall Response Rate (Complete Response (CR) + Partial Response (PR))
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
Measured: 6 months
Secondary outcomes (1)
Number of Participants With Toxicities Associated With Capecitabine and Lapatinib
Toxicities evaluated according to NCI CTC v.3
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jul 2008 (estimated)
- Study startJul 2008
- Primary completionJul 2016
- Study completionJul 2016
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.
- Other trials for 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- GlaxoSmithKline
- Responsible party
- Sponsor
- Investigators
- Tiffany Traina, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00721630
- Sponsor's protocol ID
- 08-025
- Status last verified
- Jul 2016
- First submitted
- 22 Jul 2008
- Last updated
- 15 Aug 2017
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 15 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of a Novel Capecitabine Dosing Schedule in Combination With Lapatinib, Based on the Norton-Simon Mathematical Method in Patients With HER2 Overexpressed/Amplified, Trastuzumab (Herceptin) -Refractory, Metastatic Breast Cancer
- ClinicalTrials.gov ID
- NCT00721630
- Acronym / sponsor ID
- 08-025
- Conditions
- Breast Cancer
- Keywords
- CAPECITABINE, LAPATINIB
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Collaborators
- GlaxoSmithKline
- Study start
- Jul 2008
- Primary completion
- Jul 2016 (actual)
- Study completion
- Jul 2016 (actual)
- First posted
- 24 Jul 2008 (estimated)
- Results
- Posted 15 Aug 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
HER2 is a protein that sits on the surface of breast cancer cells in some people. Because you are one of these people, your breast cancer is called "HER2-positive." The HER2 protein is involved in the growth of your breast cancer. Certain drugs can interfere with the ability of the HER2 protein to cause breast cancer growth. Trastuzumab is one of these drugs. You must have already received trastuzumab as treatment for your breast cancer to be considered for this study.
Other drugs are being studied in women with HER2-positive breast cancer. Lapatinib (Tykerb™) blocks signals that stimulate HER2-positive breast cancers to grow. The FDA approved lapatinib for use with capecitabine (Xeloda™) in patients who have metastatic breast cancer that has grown or spread after treatment with trastuzumab.
Capecitabine was approved by the FDA in 1998 for treating metastatic breast cancer. Capecitabine is a pill that blocks the way cancer cells multiply and grow. Usually, this medicine is taken twice a day for fourteen days. Then, patients do not take the pill for seven days. With this schedule and dose, some patients have had side effects that interfered with their comfort. We have used mathematical models to recommend a new schedule of capecitabine. In animals, 7 days of treatment with capecitabine followed by a 7-day break was safer and more active against breast cancer. The purpose of this study is to find out what effect (both good and bad) capecitabine has on you and your breast cancer when given in this new schedule and combined with lapatinib.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: capecitabine, lapatinibThe regimen consists of capecitabine 2,000mg twice daily for 7 days followed by a 7-day rest in combination with lapatinib 1,250mg orally daily. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- Patients with a diagnosis of invasive adenocarcinoma of the breast confirmed by histology or cytology at MSKCC.
- Clinical evidence of metastatic breast cancer.
- HER2 overexpression and/or amplification as determined by immunohistochemistry (3+) or FISH (≥2.0).
- Progressive disease following treatment with trastuzumab for metastatic breast cancer or as adjuvant therapy (either single-agent or combination therapy)
- Prior therapy inclusion:
Key exclusion criteria (11 listed)
- Patients may not be receiving any concurrent anticancer therapy or investigational agents with the intention of treating breast cancer.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to lapatinib or capecitabine.
- Known DPD deficiency.
- Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction within 6 months of study entry, uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant women are excluded from this study because lapatinib is member of the 4- anilinoquinazoline class of kinase inhibitors with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with lapatinib, breastfeeding should be discontinued if the mother is treated with lapatinib.
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 |
|---|---|---|
| capecitabine, lapatinibCapecitabine 2,000mg twice daily for 7 days followed by a 7-day rest in combination with lapatinib 1,250mg orally daily. Cycle length is 28 days (+/- 2 days).Toxicity assessment will occur q2 weeks for the first 4 weeks, then q4 weeks(+/- 2 days). Radiographic response assessment will take place q12 weeks (+/- 1 week). LVEF assessment will be repeated q12 weeks (+/- 1 week). | Drug | 1 |
Primary outcome
Estimate Efficacy of Capecitabine 7/7 in Combination With Lapatinib in Patients With HER2 Overexpressed/Amplified, Trastuzumab-refractory, Metastatic Breast Cancer as Determined by Overall Response Rate (Complete Response (CR) + Partial Response (PR))
Time frame: 6 months
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
1 secondary outcome
Number of Participants With Toxicities Associated With Capecitabine and Lapatinib
Time frame: 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Aug 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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.
Tiffany Traina, MD principal investigator
Memorial Sloan Kettering Cancer Center
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing capecitabine, lapatinib in people with Breast Cancer, run by Memorial Sloan Kettering 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 24 inclusion and 11 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 15 Aug 2017. 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?
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 15 Aug 2017). 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?
Estimate Efficacy of Capecitabine 7/7 in Combination With Lapatinib in Patients With HER2 Overexpressed/Amplified, Trastuzumab-refractory, Metastatic Breast Cancer as Determined by Overall Response Rate (Complete Response (CR) + Partial Response (PR)) (time frame: 6 months). 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 15 Aug 2017.