Breast CancerPhase 1/2NCT01118975
GCC 0845:Vorinostat and Lapatinib in Advanced Solid Tumors and Advanced Breast Cancer to Evaluate Response and Biomarkers
A Phase 1/2 study testing Vorinostat and Lapatinib in people with Breast Cancer and Neoplasm Metastasis, run by University of Maryland, Baltimore at 1 site in United States.
Trial summary
This research is being done to find out how safe and how well the combination of lapatinib and vorinostat works against advanced cancers. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer, Neoplasm Metastasis
- What is being tested?
- Vorinostat and Lapatinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2010to Oct 2012
- Phase
- Phase 1/2
- 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
- Age greater than or equal to 18 years.
- Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2.
- Consent for peripheral blood sampling for analysis of circulating tumor cells.
- Patients must have adequate organ and marrow function as defined by the protocol.
- Female patients with histologically confirmed adenocarcinoma of the breast with recurrent local-regional disease, or metastatic disease that have progressed after treatment with regimens that include an anthracycline, a taxane, or trastuzumab.
- Human Epidermal growth factor Receptor 2 (HER2) positive in the primary or secondary tumor tissue as defined by:
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- Grade 3plus staining intensity (on a scale of 0 to 3) by means of Immunohistochemistry (IHC) analysis OR
- Gene amplification on fluorescence in situ hybridization (FISH) greater than or equal to 2.2.
- Patients must have measurable disease by the Response Evaluation Criteria In Solid Tumors (RECIST)criteria at the time of enrollment.
- Prior trastuzumab therapy is allowed. Trastuzumab should be stopped at least 4 weeks prior to enrollment.
Who cannot join
- Patients receiving any other investigational agents.
- Prior exposure to lapatinib, vorinostat, or other Histone deacetylase (HDAC) inhibitors. Prior valproic acid exposure is allowed providing this is a greater than or equal to 30 days wash-out period.
- History of allergic reactions or hypersensitivity to compounds of similar chemical or biologic composition to vorinostat or lapatinib.
- Patients with history of clinically significant or uncontrolled cardiac disease, as defined by the protocol, or any significant cardiac condition that in the judgment of the investigator is unsuitable.
- Significant chronic or recent (less than 30 days) acute gastrointestinal disorder with diarrhea as a major symptom (e.g. Crohn's disease, malabsorption, or Grade 2 or greater diarrhea of any etiology at baseline).
- Prior exposure to more than 360 mg/m2 doxorubicin or liposomal doxorubicin, more than 120 mg/m2 mitoxantrone, or more than 90 mg/m2 idarubicin, or elevated baseline cardiac troponin T (more than upper limit of normal).
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- Patients with active Central Nervous System (CNS) metastasis and/or carcinomatous meningitis are excluded. Patients with CNS metastasis who have completed a course of therapy would be eligible for the study provided they are clinically stable for 3 weeks prior to entry as defined as: (1) no evidence of new or enlarging CNS metastasis and (2) off steroids and/or anticonvulsants, for at least 4 weeks before an enrollment.
- Female patient that is pregnant or breastfeeding or expecting to conceive during the study. Women able to have children must have a negative pregnancy test prior to enrollment. All patients must use two effective methods of contraception (including a barrier method) during treatment and for 12 weeks after stopping treatment.
- The patient is known to be Human immunodeficiency virus (HIV), Hepatitis B, or Hepatitis C-positive (test results are not required in order to participate).
- Patients with current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)
- Uncontrolled 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 requirement.
- Previous or current systemic malignancy within the past 3 years other than the following: Female- breast cancer or adequately treated carcinoma in-situ of the cervix, or Female and Male- basal/squamous carcinoma of the skin.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Maryland Greenebaum Cancer Center
Baltimore, Maryland, 21201
About this study
Official title: GCC 0845: Pilot and Phase II- Vorinostat and Lapatinib in Patients With Advanced Solid Tumor Malignancies and Women With Recurrent Local-Regional or Metastatic Breast Cancer to Evaluate Response and Biomarkers of EMT and Breast Cancer Stem Cells
This research is being done to find out how safe and how well the combination of lapatinib and vorinostat works against advanced cancers.
Read the detailed description
Lapatinib is an anti-cancer drug that is approved by the Food and Drug Administration (FDA) for the treatment of metastatic HER2-positive breast cancer. HER2 is a protein involved in the growth of some cancer cells. In lab tests and small clinical studies, lapatinib is also found to kill other types of cancer that have another related protein called epidermal growth factor receptor (EGFR). For participants who have other cancers, the use of lapatinib in this study is investigational. This means the drug is not FDA approved for this use.
Vorinostat is only FDA approved for the treatment of cutaneous T cell lymphoma (a type of cancer). Vorinostat is not currently FDA approved for breast cancer or any other type of cancer. The use of vorinostat in this study is investigational.
Cancer cells can travel through the blood stream and spread to other organs. This process is called metastasis. Lab tests and small clinical trials have shown that vorinostat kills some cancer cells and prevents these cancer cells from traveling through the blood stream. These trials have shown that vorinostat improves how well lapatinib kills cancer cells.
Newer studies have also shown that a subset of cells, called "cancer stem cells," can come back, spread, and become resistant to the usual chemotherapy. In laboratory tests, we found that vorinostat and lapatinib can reduce the number of cancer stem cells. We are looking at combining vorinostat and lapatinib in the hope that we can reduce the number of cancer stem cells and cancer cells traveling through the blood stream.
There are two parts to this study.
First part- We want to learn more about the best dose of vorinostat to be given with lapatinib. We want to learn about how much vorinostat and lapatinib goes into the blood during treatment. We also want to learn the side effects (safety) of the combination of vorinostat and lapatinib. All patients will receive the FDA-approved dose of lapatinib. The first group of patients will get a slightly lower dose of vorinostat than is given normally. If the side effects are not too serious, the next group of patients will get the dose of vorinostat that is given normally.
Second part- We will find out how well the combination of vorinostat and lapatinib works in patients with HER2-positive metastatic breast cancer.
- Conditions
- Breast Cancer, Neoplasm Metastasis
- Being tested
- Vorinostat, Lapatinib
- Keywords
- lapatinib ditosylate, Zolinza (vorinostat), Cancer Stem Cells
- 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.
VorinostatDrug
Also called Zolinza
300 mg 4 days on then 3 days off
As defined in the protocol, the dose of vorinostat was increased to 400 mg 4 days on then 3 days off in the pilot phase because the adverse event threshold was not met. In the Phase II cohort, the dose of vorinistat was 400 mg 4 days on and 3 days off.
LapatinibDrug
Also called Tykerb
1,250 mg once daily
| Study group | Role | What they receive |
|---|---|---|
| Pilot Phase - Vornistat 200 to 400mg + Lapatinib | Experimental | lapatinib 1,250 mg continuous daily and escalating doses of vorinistat (200mg run-up, 300mg, and 400mg 4 days on 3 days off) Receives: Drug: Vorinostat; Drug: Lapatinib |
| Phase II - Vorinistat 400mg + Lapatinib | Experimental | lapatinib 1,250 mg continuous daily and vorinostat 400 mg 4 days on 3 days Receives: Drug: Vorinostat; Drug: Lapatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose Limiting Toxicities
Safety and tolerability were assessed. Adverse events and dose limiting toxicities were recorded during an escalting dose pilot phase.
Measured: 6 weeks
Clinical Benefit Rate
The Clinical Benefit Rate is the number of patients with either Complete Response (CR), Partial Response (PR), or Stable Disease (SD) for ≥ 6 months
Measured: Radiological evaluations are performed every 12 weeks to determine disease status
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 May 2010 (estimated)
- Study startMar 2010
- Primary completionOct 2012
- Study completionOct 2012
Why it stopped: Lost sponsorship for study drug
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 University of Maryland, BaltimoreThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Maryland, Baltimore
- Sponsor type
- University, hospital or other
- Collaborators
- University of Maryland Greenebaum Cancer Center
- Responsible party
- Sponsor
- Investigators
- Saranya Chumsri, MD, Principal investigator, University of Maryland, College Park
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01118975
- Sponsor's protocol ID
- HP-00040048
- Status last verified
- Oct 2019
- First submitted
- 5 May 2010
- Last updated
- 13 Nov 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 13 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- GCC 0845: Pilot and Phase II- Vorinostat and Lapatinib in Patients With Advanced Solid Tumor Malignancies and Women With Recurrent Local-Regional or Metastatic Breast Cancer to Evaluate Response and Biomarkers of EMT and Breast Cancer Stem Cells
- ClinicalTrials.gov ID
- NCT01118975
- Acronym / sponsor ID
- HP-00040048
- Conditions
- Breast Cancer, Neoplasm Metastasis
- Keywords
- lapatinib ditosylate, Zolinza (vorinostat), Cancer Stem Cells
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lost sponsorship for study drug
- Enrolment
- 12 participants (actual)
- Lead sponsor
- University of Maryland, BaltimoreUniversity, hospital or other
- Collaborators
- University of Maryland Greenebaum Cancer Center
- Study start
- Mar 2010
- Primary completion
- Oct 2012 (actual)
- Study completion
- Oct 2012 (actual)
- First posted
- 7 May 2010 (estimated)
- Results
- Posted 24 Apr 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This research is being done to find out how safe and how well the combination of lapatinib and vorinostat works against advanced cancers.
Detailed description
Lapatinib is an anti-cancer drug that is approved by the Food and Drug Administration (FDA) for the treatment of metastatic HER2-positive breast cancer. HER2 is a protein involved in the growth of some cancer cells. In lab tests and small clinical studies, lapatinib is also found to kill other types of cancer that have another related protein called epidermal growth factor receptor (EGFR). For participants who have other cancers, the use of lapatinib in this study is investigational. This means the drug is not FDA approved for this use.
Vorinostat is only FDA approved for the treatment of cutaneous T cell lymphoma (a type of cancer). Vorinostat is not currently FDA approved for breast cancer or any other type of cancer. The use of vorinostat in this study is investigational.
Cancer cells can travel through the blood stream and spread to other organs. This process is called metastasis. Lab tests and small clinical trials have shown that vorinostat kills some cancer cells and prevents these cancer cells from traveling through the blood stream. These trials have shown that vorinostat improves how well lapatinib kills cancer cells.
Newer studies have also shown that a subset of cells, called "cancer stem cells," can come back, spread, and become resistant to the usual chemotherapy. In laboratory tests, we found that vorinostat and lapatinib can reduce the number of cancer stem cells. We are looking at combining vorinostat and lapatinib in the hope that we can reduce the number of cancer stem cells and cancer cells traveling through the blood stream.
There are two parts to this study.
First part- We want to learn more about the best dose of vorinostat to be given with lapatinib. We want to learn about how much vorinostat and lapatinib goes into the blood during treatment. We also want to learn the side effects (safety) of the combination of vorinostat and lapatinib. All patients will receive the FDA-approved dose of lapatinib. The first group of patients will get a slightly lower dose of vorinostat than is given normally. If the side effects are not too serious, the next group of patients will get the dose of vorinostat that is given normally.
Second part- We will find out how well the combination of vorinostat and lapatinib works in patients with HER2-positive metastatic breast cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pilot Phase - Vornistat 200 to 400mg + Lapatinib | Experimental | Drug: Vorinostat, Drug: Lapatiniblapatinib 1,250 mg continuous daily and escalating doses of vorinistat (200mg run-up, 300mg, and 400mg 4 days on 3 days off) |
| Phase II - Vorinistat 400mg + Lapatinib | Experimental | Drug: Vorinostat, Drug: Lapatiniblapatinib 1,250 mg continuous daily and vorinostat 400 mg 4 days on 3 days |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Age greater than or equal to 18 years.
- Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2.
- Consent for peripheral blood sampling for analysis of circulating tumor cells.
- Patients must have adequate organ and marrow function as defined by the protocol.
- Female patients with histologically confirmed adenocarcinoma of the breast with recurrent local-regional disease, or metastatic disease that have progressed after treatment with regimens that include an anthracycline, a taxane, or trastuzumab.
Key exclusion criteria (12 listed)
- Patients receiving any other investigational agents.
- Prior exposure to lapatinib, vorinostat, or other Histone deacetylase (HDAC) inhibitors. Prior valproic acid exposure is allowed providing this is a greater than or equal to 30 days wash-out period.
- History of allergic reactions or hypersensitivity to compounds of similar chemical or biologic composition to vorinostat or lapatinib.
- Patients with history of clinically significant or uncontrolled cardiac disease, as defined by the protocol, or any significant cardiac condition that in the judgment of the investigator is unsuitable.
- Significant chronic or recent (less than 30 days) acute gastrointestinal disorder with diarrhea as a major symptom (e.g. Crohn's disease, malabsorption, or Grade 2 or greater diarrhea of any etiology at baseline).
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 |
|---|---|---|
| VorinostatAlso: Zolinza300 mg 4 days on then 3 days off As defined in the protocol, the dose of vorinostat was increased to 400 mg 4 days on then 3 days off in the pilot phase because the adverse event threshold was not met. In the Phase II cohort, the dose of vorinistat was 400 mg 4 days on and 3 days off. | Drug | Phase II - Vorinistat 400mg + Lapatinib, Pilot Phase - Vornistat 200 to 400mg + Lapatinib |
| LapatinibAlso: Tykerb1,250 mg once daily | Drug | Phase II - Vorinistat 400mg + Lapatinib, Pilot Phase - Vornistat 200 to 400mg + Lapatinib |
Primary outcome
Dose Limiting Toxicities
Time frame: 6 weeks
Safety and tolerability were assessed. Adverse events and dose limiting toxicities were recorded during an escalting dose pilot phase.
Clinical Benefit Rate
Time frame: Radiological evaluations are performed every 12 weeks to determine disease status
The Clinical Benefit Rate is the number of patients with either Complete Response (CR), Partial Response (PR), or Stable Disease (SD) for ≥ 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Nov 2019.
- 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.
Saranya Chumsri, MD principal investigator
University of Maryland, College Park
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Vorinostat and Lapatinib in people with Breast Cancer and Neoplasm Metastasis, run by University of Maryland, Baltimore 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 10 inclusion and 12 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 13 Nov 2019. 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 combined 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.
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 24 Apr 2014). 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?
Dose Limiting Toxicities (time frame: 6 weeks). 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 13 Nov 2019.