Advanced Solid TumorsPhase 1NCT01497626
Lapatinib and Bortezomib in Patients With Advanced Malignancies
A Phase 1 study testing Lapatinib and bortezomib in people with Advanced Solid Tumors, run by Georgetown University at 1 site in United States.
Trial summary
This study is for patients with an advanced type of cancer for which no curative treatment exists. The purpose of this study is to test the safety and efficacy of the combination of the study drugs, lapatinib and bortezomib. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumors
- What is being tested?
- Lapatinib and bortezomib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2011to Dec 2015
- 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
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically proven malignant solid tumor with measurable disease
- Progression on, or intolerance of, or ineligibility for all standard therapies
- Biopsy accessible tumor deposits
- LVEF >/= institutional normal
- Corrected QT interval less than 500 milliseconds by EKG
- ECOG performance status 0-2
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- Subjects with no brain metastases or a history of previously treated brain metastases who have been treated by surgery or stereotactic radiosurgery at least 4 weeks prior to enrollment and have a baseline MRI that shows no evidence of active intercranial disease and have not had treatment with steroids within 1 week of enrollment.
- Adequate hepatic, bone marrow, and renal function
- Partial thromboplastin time must be </= 1.5 x upper limit of institution's normal range and INR < 1.5. Subjects on anticoagulants will be permitted to enroll as long as the INR is in the acceptable therapeutic range.
- Life expectancy > 12 weeks
- Women of childbearing potential must have a negative serum pregnancy test within 14 days prior to initiation of treatment and/or postmenopausal women must be amenorrheic for at least 12 months.
- Subject is capable of understanding and complying with parameters as outlines in the protocol and able to sign and date the informed consent form.
Who cannot join
- Patients with lymphomas
- CNS metastases which do not meet the criteria outlines in the inclusion criteria
- Peripheral neuropathy >/= Grade 2 at baseline or peripheral neuropathy >/= Grade 1 with neuropathic pain
- Active severe infection or known chronic infection with HIV or hepatitis B virus
- Cardiovascular disease problems including unstable angina, therapy for life-threatening ventricular arrhythmia, or myocardial infarction, stroke, or congestive heart failure within the last 6 months
- Life-threatening visceral disease or other severe concurrent disease
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- Women who are pregnant or breastfeeding
- Anticipated patient survival under 3 months
- Concurrent use of known CYP 3A4 inhibiting or activating medications
Trial locations and contacts
1 site in 1 country.
United States1 site
Georgetown Lombardi Comprehensive Cancer Center
Washington D.C., District of Columbia, 20007
About this study
Official title: A Phase I Study of the HER1, HER2 Dual Kinase Inhibitor, Lapatinib Plus the Proteosomal Inhibitor Bortezomib in Patients With Advanced Malignancies
This study is for patients with an advanced type of cancer for which no curative treatment exists.
The purpose of this study is to test the safety and efficacy of the combination of the study drugs, lapatinib and bortezomib. Lapatinib is a drug that targets two proteins important for the growth of cancer cells known as HER1 (EGFR) and HER2. By inhibiting these proteins, lapatinib can inhibit cancer cell growth and even lead to their death. Lapatinib is an oral pill given by mouth once every day. Lapatinib is approved by the FDA for patients with breast cancer.
Read more
Bortezomib is a drug that targets a part of cancer cells known as the proteosome. By inhibiting the proteosome, bortezomib can inhibit cancer cell growth and even lead to their death. Bortezomib is given intravenously, once a week, 2 out of every 3 weeks. Bortezomib is approved by the FDA for patients with multiple myeloma and mantle cell lymphoma.
This research is being done because it is not known if the combination of lapatinib and bortezomib will work better than lapatinib or bortezomib alone, although in the lab and in animal studies the combination of the two drugs was much more effective than either drug alone.
As part of this study biopsies will be taken of patients' tumors before any treatment, after starting lapatinib alone, and after receiving both lapatinib and bortezomib. Investigators want to study what markers inside tumors may relate to how well these two medications work. These biopsies are required as part of the study.
- Conditions
- Advanced Solid Tumors
- Being tested
- Lapatinib and bortezomib
- Keywords
- Advanced cancer, Solid tumor
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lapatinib and bortezomibDrug
Also called Velcade
Lapatinib will be taken orally continuously for 28 days of each 28-day cycle, including a run-in of lapatinib alone day -7 to day 1 of cycle 1.
Bortezomib will be administered IV on days 1, 8, and 15 of each cycle. The exact doses of both drugs will be dependent on which cohort the subject is in and adverse events observed in previous cohorts.
| Study group | Role | What they receive |
|---|---|---|
| Bortezomib plus lapatinib | Experimental | Combination treatment with lapatinib and bortezomib Receives: Drug: Lapatinib and bortezomib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose
The highest dose at which </= 1 out of 6 subjects has a dose-limiting toxicity
Measured: 18 months
Secondary outcomes (4)
toxicity
Adverse events seen during the trial graded using CTCAE version 4
Measured: 18 months
Response rate
complete response and partial response measured by RECIST 1.1
Measured: 18 months
Disease control rate
stable disease after two cycles+ partial response + complete response as determined by RECIST 1.1 criteria
Measured: 2 months
Pharmacodynamics
To assess changes in the following in serial tumor samples: EGFR, HER2, HER3, AKT, Actin, ERK, GSK3a-beta, IGF-1R, MEK 1/2, mTOR, p70S6, P13K, PTEN, SHC Y317, NFKB, IKB, CFK4, CDK2, cyclin D1, cyclin A, Cyclin E, p15, p16, p21, p27, beta-catenin, and ras gene mutation
Measured: pre-treatment, after 1 week of therapy and adter 3 weeks of therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Dec 2011 (estimated)
- Study startSep 2011
- Primary completionDec 2015
- Study completionDec 2015
Why it stopped: Drug support withdrawn
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 Advanced Solid TumorsStudies of the same condition, open and under way.
- More trials run by Georgetown UniversityThe 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
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Georgetown University
- Sponsor type
- University, hospital or other
- Collaborators
- GlaxoSmithKline, Millennium Pharmaceuticals, Inc.
- Responsible party
- Sponsor
- Investigators
- Michael Pishvaian, MD PhD, Principal investigator, Georgetown University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01497626
- Sponsor's protocol ID
- 2010-533
- Other IDs
- XO5371, 8LAP114999
- Status last verified
- Sep 2015
- First submitted
- 20 Dec 2011
- Last updated
- 17 Feb 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Lynce F, Wang H, Petricoin EF, Pohlmann PR, Smaglo B, Hwang J, He AR, Subramaniam DS, Deeken J, Marshall J, Pishvaian MJ. A phase I study of HER1, HER2 dual kinase inhibitor lapatinib plus the proteasome inhibitor bortezomib in patients with advanced malignancies. Cancer Chemother Pharmacol. 2019 Nov;84(5):1145-1151. doi: 10.1007/s00280-019-03947-7. Epub 2019 Sep 19.
PubMed 31538230
Study at a glance
From the registry record, last updated by the sponsor on 17 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of the HER1, HER2 Dual Kinase Inhibitor, Lapatinib Plus the Proteosomal Inhibitor Bortezomib in Patients With Advanced Malignancies
- ClinicalTrials.gov ID
- NCT01497626
- Acronym / sponsor ID
- 2010-533
- Conditions
- Advanced Solid Tumors
- Keywords
- Advanced cancer, Solid tumor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Drug support withdrawn
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Georgetown UniversityUniversity, hospital or other
- Collaborators
- GlaxoSmithKline, Millennium Pharmaceuticals, Inc.
- Study start
- Sep 2011
- Primary completion
- Dec 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 22 Dec 2011 (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.
This study is for patients with an advanced type of cancer for which no curative treatment exists.
The purpose of this study is to test the safety and efficacy of the combination of the study drugs, lapatinib and bortezomib. Lapatinib is a drug that targets two proteins important for the growth of cancer cells known as HER1 (EGFR) and HER2. By inhibiting these proteins, lapatinib can inhibit cancer cell growth and even lead to their death. Lapatinib is an oral pill given by mouth once every day. Lapatinib is approved by the FDA for patients with breast cancer.
Bortezomib is a drug that targets a part of cancer cells known as the proteosome. By inhibiting the proteosome, bortezomib can inhibit cancer cell growth and even lead to their death. Bortezomib is given intravenously, once a week, 2 out of every 3 weeks. Bortezomib is approved by the FDA for patients with multiple myeloma and mantle cell lymphoma.
This research is being done because it is not known if the combination of lapatinib and bortezomib will work better than lapatinib or bortezomib alone, although in the lab and in animal studies the combination of the two drugs was much more effective than either drug alone.
As part of this study biopsies will be taken of patients' tumors before any treatment, after starting lapatinib alone, and after receiving both lapatinib and bortezomib. Investigators want to study what markers inside tumors may relate to how well these two medications work. These biopsies are required as part of the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Bortezomib plus lapatinib | Experimental | Drug: Lapatinib and bortezomibCombination treatment with lapatinib and bortezomib |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Histologically proven malignant solid tumor with measurable disease
- Progression on, or intolerance of, or ineligibility for all standard therapies
- Biopsy accessible tumor deposits
- LVEF >/= institutional normal
- Corrected QT interval less than 500 milliseconds by EKG
Key exclusion criteria (9 listed)
- Patients with lymphomas
- CNS metastases which do not meet the criteria outlines in the inclusion criteria
- Peripheral neuropathy >/= Grade 2 at baseline or peripheral neuropathy >/= Grade 1 with neuropathic pain
- Active severe infection or known chronic infection with HIV or hepatitis B virus
- Cardiovascular disease problems including unstable angina, therapy for life-threatening ventricular arrhythmia, or myocardial infarction, stroke, or congestive heart failure within the last 6 months
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 and bortezomibAlso: VelcadeLapatinib will be taken orally continuously for 28 days of each 28-day cycle, including a run-in of lapatinib alone day -7 to day 1 of cycle 1. Bortezomib will be administered IV on days 1, 8, and 15 of each cycle. The exact doses of both drugs will be dependent on which cohort the subject is in and adverse events observed in previous cohorts. | Drug | Bortezomib plus lapatinib |
Primary outcome
Maximum tolerated dose
Time frame: 18 months
The highest dose at which </= 1 out of 6 subjects has a dose-limiting toxicity
4 secondary outcomes
toxicity
Time frame: 18 months
Response rate
Time frame: 18 months
Disease control rate
Time frame: 2 months
Pharmacodynamics
Time frame: pre-treatment, after 1 week of therapy and adter 3 weeks of therapy
Results and safety
The study was stopped early (reason given: Drug support withdrawn). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Feb 2016.
- Derived from this study: PubMed 31538230Lynce F, Wang H, Petricoin EF, Pohlmann PR, Smaglo B, Hwang J, He AR, Subramaniam DS, Deeken J, Marshall J, Pishvaian MJ. A phase I study of HER1, HER2 dual kinase inhibitor lapatinib plus the proteasome inhibitor bortezomib in patients with advanced malignancies. Cancer Chemother Pharmacol. 2019 Nov;84(5):1145-1151. doi: 10.1007/s00280-019-03947-7. Epub 2019 Sep 19.
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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.
Michael Pishvaian, MD PhD principal investigator
Georgetown University
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 Lapatinib and bortezomib in people with Advanced Solid Tumors, run by Georgetown University 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 12 inclusion and 9 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 17 Feb 2016. 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?
The study was stopped early (reason given: Drug support withdrawn). Results are not available in the source record.
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 (time frame: 18 months). 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 NCT01497626, 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 17 Feb 2016.