Breast CancerPhase 1NCT00632489
LBH589 in Combination With Capecitabine Plus/Minus (±) Lapatinib in Breast Cancer Patients
A Phase 1 study testing LBH589, Capecitabine and Lapatinib in people with Breast Cancer, run by SCRI Development Innovations, LLC at 1 site in United States.
Trial summary
This single center Phase I dose escalation trial will evaluate the safety, tolerability and efficacy of LBH589 when combined with capecitabine and lapatinib in three parts. Part 1 will determine the maximum tolerated doses (MTD) of LBH589 when combined with capecitabine. 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?
- LBH589, Capecitabine and Lapatinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- May 2008to Jul 2011
- Phase
- Phase 1
- 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
- Histologically documented metastatic or locally unresectable, incurable malignancy for which capecitabine is clinically appropriate.
- Male or female patients aged ≥ 18 years old.
- Maximum of 3 prior regimens in a metastatic setting allowed and may include other targeted agents, immunotherapy and chemotherapy.
- Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
- Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1.
- Baseline MUGA or ECHO must demonstrate LVEF > than the lower limits of the institutional normal.
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- Laboratory values as follows:
- ANC > 1500/μL
- Hgb > 9 g/dL
- Platelets > 100,000/uL
- Bilirubin < 1.5 mg/dL
- AST/SGOT < 2.5 x ULN or < 5.0 x ULN and ALT/SGPT in patients with liver metastases
- Creatinine < 1.5 mg/dL or calculated creatinine clearance > 50 ml/min
- Albumin > 3 g/dL
- Potassium > lower limit of normal (LLN)
- Phosphorous > LLN
- Calcium > LLN
- Magnesium > LLN
- Women of childbearing potential must have a negative serum or urine pregnancy test performed within 7 days prior to start of treatment and must commit to begin two acceptable methods of birth control, one highly effective method of birth control and one additional effective method at the same time before starting treatment.
- Life expectancy > 12 weeks.
- Accessible for treatment and follow-up.
- All patients must be able to understand the nature of the study and give written informed consent prior to study entry.
- Additional Breast Cancer Patient Subset (Part 2 and Part 3) Inclusion Criteria:
- Incurable carcinoma of the breast, with measurable locally recurrent or metastatic disease.
- ICH 3+ overexpression or FISH amplification documented by a local laboratory in primary or metastatic tumor tissue.
- Prior treatment with an anthracycline, taxane, and trastuzumab or not a candidate for such treatment. Patient may have received these drugs in combination or in sequence for the treatment of locally advanced or metastatic disease and/or adjuvant therapy.
Who cannot join
- Prior treatment with an HDAC inhibitor or current treatment with valproic acid.
- Previous treatment with capecitabine.
- Impaired cardiac function including any of the following:
- Screening ECG with a QTc > 450 msec.
- Congenital long QT syndrome.
- History of sustained ventricular tachycardia.
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- Any history of ventricular fibrillation or torsades de pointes.
- Bradycardia defined as heart rate < 50 beats per minute. Patients with a pacemaker and heart rate > 50 beats per minute are eligible.
- Myocardial infarction or unstable angina within 6 months of study entry.
- Congestive heart failure (NY Heart Association class III or IV).
- Right bundle branch block and left anterior hemiblock (bifascicular block).
- Atrial fibrillation or flutter.
- Ongoing therapy with antiarrhythmics or other medications associated with QTc prolongation.
- Uncorrected hypokalemia or hypomagnesaemia.
- Uncontrolled hypertension (systolic blood pressure [BP] 180 or diastolic BP > 100 mm Hg) or uncontrolled cardiac arrhythmias.
- Active CNS disease, including meningeal metastases.
- Known diagnosis of human immunodeficiency virus (HIV) infection.
- Unresolved diarrhea > CTCAE grade 1.
- Concomitant requirement for medication classified as CYP3A4 inducers or inhibitors.
- Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to lapatinib.
- Patients with known hypersensitivity to 5-fluorouracil chemotherapy, investigational drug therapy, major surgery < 4 weeks prior to starting study drug or patients that have not recovered from side effects of previous therapy.
- Patient is < 5 years free of another primary malignancy except if the other primary malignancy is not currently clinically significant or requiring active intervention, or if other primary malignancy is a basal cell skin cancer or a cervical carcinoma in situ. Existence of any other malignant disease is not allowed.
- Concomitant use of any anti-cancer therapy or radiation therapy.
- Pregnant or breast feeding or female of reproductive potential not using two effective methods of birth control.
- Male patients whose sexual partners are women of childbearing potential not using effective birth control.
- Patients with gastrointestinal (GI) tract disease, causing the inability to take oral medication, malabsorption syndrome, a requirement for intravenous (IV) alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease (e.g., Crohn's disease, ulcerative colitis).
- Other concurrent severe, uncontrolled infection or intercurrent illness, including but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Patients taking any medications listed in "Prohibited Medications" for both capecitabine and lapatinib .
- Patients with uncontrolled coagulopathy (PT and/or PTT > 1.2 x ULN; patient must also be on stable dose of anticoagulant for a defined medical indication).
- Abnormal thyroid function (TSH or free T4) detected at screening. Patients with known hypothyroidism who are stable on thyroid replacement are eligible.
- Additional Breast Cancer Patient Subset (Part 2 and Part 3) Exclusion Criteria:
- 1. Prior treatment with lapatinib
Trial locations and contacts
1 site in 1 country.
United States1 site
Tennessee Oncology, PLLC
Nashville, Tennessee, 37023
About this study
Official title: A Phase I Study of LBH589 in Combination With Capecitabine ± Lapatinib
This single center Phase I dose escalation trial will evaluate the safety, tolerability and efficacy of LBH589 when combined with capecitabine and lapatinib in three parts. Part 1 will determine the maximum tolerated doses (MTD) of LBH589 when combined with capecitabine. Parts 2 and 3 will be limited to locally recurrent or metastatic breast cancer patients, ICH 3+ overexpression or FISH amplification documented locally. Part 2 will evaluate the safety of the MTD of LBH589 determined in Part 1 when paired with lapatinib 1000 mg by mouth (PO) daily. Parts 2 and 3 will be limited to locally recurrent or metastatic breast cancer patients, ICH 3+ overexpression or FISH amplification documented locally. Part 3 will evaluate the tolerability and effectiveness of the triplet combination, LBH589, capecitabine and lapatinib in breast cancer patients.
Read the detailed description
LBH589 will be evaluated when administered twice weekly at the following possible dose levels: 20 mg, 30 mg, 45 mg, and 60 mg. Capecitabine will be paired with LBH589 and will range in dose from 825 mg/m2 to 1250 mg/m2 orally BID 14 of every 21 days. Treatment cycles will be 21 days in length. Once determined safe, 10 additional patients will be treated at the determined MTD to further assess safety.
The second portion of this study will assess QTc prolongation with the LBH589 and lapatinib combination. A subset of 6 patients will be treated with the LBH589 one dose below the MTD determined during Part I. If tolerated, 6 additional patients will receive LBH589 at the MTD established in Part I with lapatinib (capecitabine will not be administered in this subset of patients).
If there are no clinically significant findings in the LBH589 and lapatinib subset, the study will advance to a third portion which combines the three drugs LBH589, capecitabine, and lapatinib.
The triple combination will initially administer lapatinib 1000 mg orally daily with LBH589 and capecitabine at one dose level below the established MTD. If tolerated, LBH589 and capecitabine doses will be escalated to the MTD.
Toxicity assessments will be ongoing and disease assessments will be repeated every 2 treatment cycles. If all dose level combinations are explored, a total of 45-55 patients will be required to accommodate for the additional patients enrolled in the QTc subset and to establish the recommended phase II dose of the combination regimen.
- Conditions
- Breast Cancer
- Being tested
- LBH589, Capecitabine, Lapatinib
- Keywords
- Refractory Malignancy, Breast Cancer, LBH589, Capecitabine, Lapatinib
- Medical subject headings
- Breast Neoplasms, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LBH589Drug
Also called Panobinostat
LBH589 will be evaluated when administered twice weekly at the following possible dose levels: 20 mg, 30 mg, 45 mg, and 60 mg. Capecitabine will be paired with LBH589 and will range in dose from 825 mg/m2 to 1250 mg/m2 orally BID 14 of every 21 days. Treatment cycles will be 21 days in length. Once determined safe, 10 additional patients will be treated at the determined MTD to further assess safety.
CapecitabineDrug
Also called Xeloda
Capecitabine will be administered orally twice daily for 14 days out of every 21 days.
LapatinibDrug
Also called Tykerb, Tyverb
Lapatinib, 1000 mg PO daily will be added to this combination.
| Study group | Role | What they receive |
|---|---|---|
| LBH589 with Capecitabine | Experimental | MTD, LBH589 with Capecitabine Receives: Drug: LBH589; Drug: Capecitabine |
| LBH589 and Lapatinib | Experimental | LBH589 and Lapatinib Receives: Drug: LBH589; Drug: Lapatinib |
| LBH589, Capecitabine and Lapatinib | Experimental | LBH589, Capecitabine and Lapatinib (Breast Cancer Patients) Receives: Drug: LBH589; Drug: Capecitabine; Drug: Lapatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
To Determine the Maximum Tolerated Doses (MTD) and Dose-limiting Toxicities (DLT) of LBH589 in Combination With Capecitabine When Administered to Patients With Refractory and Advanced Tumor Types That Are Sensitive to 5-fluorouracil
MTD for Capecitabine, BID
Measured: 18 months
To Determine the Maximum Tolerated Doses (MTD) and Dose-limiting Toxicities (DLT) of LBH589 in Combination With Capecitabine When Administered to Patients With Refractory and Advanced Tumor Types That Are Sensitive to 5-fluorouracil
MTD for Panobinostat, twice weekly
Measured: 18 months
Secondary outcomes (2)
To Evaluate the Antitumor Activity of LBH589 in Combination With Capecitabine in Patients With Refractory and Advanced Tumors
Measured: 18 months
To Evaluate the Tolerability and Preliminary Efficacy of Established Doses of LBH589 and Capecitabine With Lapatinib in a Limited Number of Patients With HER2+ Breast Cancer
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Mar 2008 (estimated)
- Study startMay 2008
- Primary completionJan 2009
- Study completionJul 2011
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.
- 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
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- SCRI Development Innovations, LLC
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis
- Responsible party
- Sponsor
- Investigators
- Howard A Burris, III, M.D., Study chair, SCRI Development Innovations, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00632489
- Sponsor's protocol ID
- SCRI REFMAL 119
- Status last verified
- Jun 2015
- First submitted
- 3 Mar 2008
- Last updated
- 8 Jun 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Jun 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of LBH589 in Combination With Capecitabine ± Lapatinib
- ClinicalTrials.gov ID
- NCT00632489
- Acronym / sponsor ID
- SCRI REFMAL 119
- Conditions
- Breast Cancer
- Keywords
- Refractory Malignancy, Breast Cancer, LBH589, Capecitabine, Lapatinib
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- SCRI Development Innovations, LLCUniversity, hospital or other
- Collaborators
- Novartis
- Study start
- May 2008
- Primary completion
- Jan 2009 (actual)
- Study completion
- Jul 2011 (actual)
- First posted
- 10 Mar 2008 (estimated)
- Results
- Posted 8 Jun 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This single center Phase I dose escalation trial will evaluate the safety, tolerability and efficacy of LBH589 when combined with capecitabine and lapatinib in three parts. Part 1 will determine the maximum tolerated doses (MTD) of LBH589 when combined with capecitabine. Parts 2 and 3 will be limited to locally recurrent or metastatic breast cancer patients, ICH 3+ overexpression or FISH amplification documented locally. Part 2 will evaluate the safety of the MTD of LBH589 determined in Part 1 when paired with lapatinib 1000 mg by mouth (PO) daily. Parts 2 and 3 will be limited to locally recurrent or metastatic breast cancer patients, ICH 3+ overexpression or FISH amplification documented locally. Part 3 will evaluate the tolerability and effectiveness of the triplet combination, LBH589, capecitabine and lapatinib in breast cancer patients.
Detailed description
LBH589 will be evaluated when administered twice weekly at the following possible dose levels: 20 mg, 30 mg, 45 mg, and 60 mg. Capecitabine will be paired with LBH589 and will range in dose from 825 mg/m2 to 1250 mg/m2 orally BID 14 of every 21 days. Treatment cycles will be 21 days in length. Once determined safe, 10 additional patients will be treated at the determined MTD to further assess safety.
The second portion of this study will assess QTc prolongation with the LBH589 and lapatinib combination. A subset of 6 patients will be treated with the LBH589 one dose below the MTD determined during Part I. If tolerated, 6 additional patients will receive LBH589 at the MTD established in Part I with lapatinib (capecitabine will not be administered in this subset of patients).
If there are no clinically significant findings in the LBH589 and lapatinib subset, the study will advance to a third portion which combines the three drugs LBH589, capecitabine, and lapatinib.
The triple combination will initially administer lapatinib 1000 mg orally daily with LBH589 and capecitabine at one dose level below the established MTD. If tolerated, LBH589 and capecitabine doses will be escalated to the MTD.
Toxicity assessments will be ongoing and disease assessments will be repeated every 2 treatment cycles. If all dose level combinations are explored, a total of 45-55 patients will be required to accommodate for the additional patients enrolled in the QTc subset and to establish the recommended phase II dose of the combination regimen.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| LBH589 with Capecitabine | Experimental | Drug: LBH589, Drug: CapecitabineMTD, LBH589 with Capecitabine |
| LBH589 and Lapatinib | Experimental | Drug: LBH589, Drug: LapatinibLBH589 and Lapatinib |
| LBH589, Capecitabine and Lapatinib | Experimental | Drug: LBH589, Drug: Capecitabine, Drug: LapatinibLBH589, Capecitabine and Lapatinib (Breast Cancer Patients) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (26 listed)
- Histologically documented metastatic or locally unresectable, incurable malignancy for which capecitabine is clinically appropriate.
- Male or female patients aged ≥ 18 years old.
- Maximum of 3 prior regimens in a metastatic setting allowed and may include other targeted agents, immunotherapy and chemotherapy.
- Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
- Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1.
Key exclusion criteria (32 listed)
- Prior treatment with an HDAC inhibitor or current treatment with valproic acid.
- Previous treatment with capecitabine.
- Impaired cardiac function including any of the following:
- Uncorrected hypokalemia or hypomagnesaemia.
- Uncontrolled hypertension (systolic blood pressure [BP] 180 or diastolic BP > 100 mm Hg) or uncontrolled cardiac arrhythmias.
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 |
|---|---|---|
| LBH589Also: PanobinostatLBH589 will be evaluated when administered twice weekly at the following possible dose levels: 20 mg, 30 mg, 45 mg, and 60 mg. Capecitabine will be paired with LBH589 and will range in dose from 825 mg/m2 to 1250 mg/m2 orally BID 14 of every 21 days. Treatment cycles will be 21 days in length. Once determined safe, 10 additional patients will be treated at the determined MTD to further assess safety. | Drug | LBH589 and Lapatinib, LBH589 with Capecitabine, LBH589, Capecitabine and Lapatinib |
| CapecitabineAlso: XelodaCapecitabine will be administered orally twice daily for 14 days out of every 21 days. | Drug | LBH589 with Capecitabine, LBH589, Capecitabine and Lapatinib |
| LapatinibAlso: Tykerb, TyverbLapatinib, 1000 mg PO daily will be added to this combination. | Drug | LBH589 and Lapatinib, LBH589, Capecitabine and Lapatinib |
Primary outcome
To Determine the Maximum Tolerated Doses (MTD) and Dose-limiting Toxicities (DLT) of LBH589 in Combination With Capecitabine When Administered to Patients With Refractory and Advanced Tumor Types That Are Sensitive to 5-fluorouracil
Time frame: 18 months
MTD for Capecitabine, BID
To Determine the Maximum Tolerated Doses (MTD) and Dose-limiting Toxicities (DLT) of LBH589 in Combination With Capecitabine When Administered to Patients With Refractory and Advanced Tumor Types That Are Sensitive to 5-fluorouracil
Time frame: 18 months
MTD for Panobinostat, twice weekly
2 secondary outcomes
To Evaluate the Antitumor Activity of LBH589 in Combination With Capecitabine in Patients With Refractory and Advanced Tumors
Time frame: 18 months
To Evaluate the Tolerability and Preliminary Efficacy of Established Doses of LBH589 and Capecitabine With Lapatinib in a Limited Number of Patients With HER2+ Breast Cancer
Time frame: 18 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jun 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Howard A Burris, III, M.D. study chair
SCRI Development Innovations, LLC
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 LBH589, Capecitabine and Lapatinib in people with Breast Cancer, run by SCRI Development Innovations, LLC 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 26 inclusion and 32 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 8 Jun 2015. 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?
Yes. Results are posted in the registry (first posted 8 Jun 2015). 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?
To Determine the Maximum Tolerated Doses (MTD) and Dose-limiting Toxicities (DLT) of LBH589 in Combination With Capecitabine When Administered to Patients With Refractory and Advanced Tumor Types That Are Sensitive to 5-fluorouracil (time frame: 18 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?
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 8 Jun 2015.