LymphomaPhase 1NCT00352443
S0528 Lapatinib and Everolimus in Treating Patients With Advanced Solid Tumors or Non-Hodgkin's Lymphoma
A Phase 1 study testing everolimus and lapatinib ditosylate in people with Lymphoma and Unspecified Adult Solid Tumor, Protocol Specific, run by SWOG Cancer Research Network at 6 sites in United States.
Trial summary
RATIONALE: Lapatinib and everolimus may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Everolimus may also stop the growth of cancer cells by blocking blood flow to the cancer. Giving lapatinib together with everolimus may kill more cancer cells. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lymphoma, Unspecified Adult Solid Tumor, Protocol Specific
- What is being tested?
- everolimus and lapatinib ditosylate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 66 participants
- Where
- 6 sitesUnited States
- Study dates
- Sep 2006to Sep 2013
- 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
DISEASE CHARACTERISTICS:
- Histologically or cytologically confirmed advanced solid tumor or non-Hodgkin's lymphoma for which no curative options exist
- Measurable or nonmeasurable disease
- Patients with brain metastases who require corticosteroids or anticonvulsants must be on a stable or decreasing dose of corticosteroids and seizure free for 30 days prior to study entry
- Patients with known brain metastases must have had brain irradiation (whole brain or gamma knife)
- No untreated (non-irradiated) brain metastases
PATIENT CHARACTERISTICS:
- Zubrod performance status 0-2
- Absolute neutrophil count ≥ 1,500/mm³
- Platelet count ≥ 100,000/mm³
- SGOT or SGPT ≤ 2.5 times upper limit of normal (ULN) (5 times ULN if liver metastases are present)
- Bilirubin normal
- Creatinine normal OR creatinine clearance > 60 mL/min
- Cardiac ejection fraction normal by echocardiogram or MUGA
- Able to swallow enteral medications
- No feeding tubes
- No intractable nausea or vomiting
- No gastrointestinal (GI) tract disease resulting in an inability to take oral medication
- No current active hepatic or biliary disease with the exception of Gilbert's syndrome or asymptomatic gallstones
- No malabsorption syndrome
- No requirement for IV alimentation
- No uncontrolled inflammatory GI disease (e.g., Crohn's disease, ulcerative colitis)
- No history of allergic reactions attributed to compounds of similar chemical or biologic composition to lapatinib or everolimus, including other quinazoline compounds, such as gefitinib and erlotinib, or other rapamycins, such as sirolimus and temsirolimus
- No known HIV positivity
- No concurrent uncontrolled illness, including, but not limited to, any of the following:
- Ongoing or active infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- Myocardial infarction or cerebrovascular accident within the past 3 months
- Uncontrolled diarrhea
- Psychiatric illness or social situation that would preclude compliance with study requirements
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- Willing to undergo pharmacokinetic (PK) sampling and blood collection for PK and correlative studies (for patients enrolled in part II)
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- Recovered from prior therapy
- No prior lapatinib or everolimus
- No prior surgical procedures affecting absorption
- More than 14 days since prior major surgery, chemotherapy (42 days for nitrosoureas or mitomycin C), or radiotherapy
- More than 28 days since prior investigational agents
- At least 7 days since prior and no concurrent CYP3A4 inhibitors
- At least 14 days since prior and no concurrent CYP3A4 inducers
- At least 14 days since prior and no concurrent herbal or dietary supplements
- No concurrent chemotherapy, hormone therapy, radiotherapy, immunotherapy, live vaccines or any other anticancer therapy
- Concurrent luteinizing hormone-releasing hormone agonists allowed
- Concurrent bisphosphonates or epoetin alfa or its analogue allowed
- No concurrent gastric H2 blockers (e.g., cimetidine, ranitidine, nizatidine, famotidine) or proton pump inhibitors (e.g., omeprazole, esomeprazole, rabeprazole, pantoprazole, or lansoprazole)
- Antacids allowed provided they are not administered within 1 hour before and after lapatinib
- No concurrent glucocorticoids or immunosuppressants
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, 48109-0942
University of Colorado Cancer Center at UC Health Sciences Center
Aurora, Colorado, 80045
Lucille P. Markey Cancer Center at University of Kentucky
Lexington, Kentucky, 40536-0093
USC/Norris Comprehensive Cancer Center and Hospital
Los Angeles, California, 90089-9181
University of California Davis Cancer Center
Sacramento, California, 95817
University Cancer Center at University of Washington Medical Center
Seattle, Washington, 98195-6043
About this study
Official title: Phase I Study Evaluating the Combination of Lapatinib (GW572016; NSC-727989) and Everolimus (RAD001) in Patients With Advanced Solid Tumors
RATIONALE: Lapatinib and everolimus may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Everolimus may also stop the growth of cancer cells by blocking blood flow to the cancer. Giving lapatinib together with everolimus may kill more cancer cells.
PURPOSE: This phase I trial is studying the side effects and best dose of lapatinib and everolimus in treating patients with advanced solid tumors or non-Hodgkin's lymphoma.
Read the detailed description
OBJECTIVES:
- Estimate the maximum tolerated dose (MTD) of lapatinib and everolimus in patients with advanced solid tumors or non-Hodgkin's lymphoma. (Part I)
- Investigate the pharmacokinetics of everolimus and lapatinib (when given alone and in combination) at the MTD determined in Part I. (Part II)
- Investigate the effects of everolimus and lapatinib (when given alone and in combination) on serum levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), matrix metalloproteinase (MMP)-2 and MMP-9, interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α). (Part II)
OUTLINE: This is a multicenter, dose-escalation study followed by a randomized study. Initial patients enrolled on the study are treated in part I. After the maximum tolerated dose (MTD) is determined in part I, subsequent patients are enrolled and treated in part II.
- Part I: Patients receive oral everolimus and oral lapatinib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of everolimus and lapatinib until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.
- Part II: Patients are randomized to 1 of 2 treatment arms. Everolimus and lapatinib are administered at the MTD determined in part I.
- Arm I: Patients receive oral everolimus once daily on days 1-28. Patients also receive oral lapatinib once daily on days 8-28 during the first course and on days 1-28 during all subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
- Arm II: Patients receive oral lapatinib once daily on days 1-28. Patients also receive oral everolimus once daily on days 8-28 during the first course and on days 1-28 during all subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients in part II undergo blood collection periodically for correlative biomarker and pharmacokinetic studies.
After finishing treatment, patients are followed periodically for 28 days.
PROJECTED ACCRUAL: A total of 48 patients will be accrued for this study.
- Being tested
- everolimus, lapatinib ditosylate
- Keywords
- adult grade III lymphomatoid granulomatosis, recurrent adult grade III lymphomatoid granulomatosis, Waldenstrom macroglobulinemia, recurrent adult Burkitt lymphoma, stage IV adult Burkitt lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult immunoblastic large cell lymphoma, recurrent adult lymphoblastic lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent mantle cell lymphoma, recurrent marginal zone lymphoma, recurrent small lymphocytic lymphoma, stage IV adult diffuse large cell lymphoma, stage IV adult diffuse mixed cell lymphoma, stage IV adult diffuse small cleaved cell lymphoma, stage IV adult immunoblastic large cell lymphoma
- Medical subject headings
- Lymphoma, Waldenstrom Macroglobulinemia, Burkitt Lymphoma, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Non-Hodgkin, Lymphoma, Large-Cell, Immunoblastic, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Lymphoma, Follicular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
everolimusDrug
part 1: dose assigned by ETx online system PO days 1-28 daily part 2: cohort a: 5 mg PO days 1-28 part 2: cohort a: 1250 mg PO days 8-28 (cycle 1) days 1-28 (subsequent cycles)
lapatinib ditosylateDrug
dose assigned by ETx online system PO days 1-28 daily part 2 cohort a: 1250 mg PO d 8-28 (cycle 1) days 1-28 (subsequent cycles) part 2 cohort b: 120 mg PO days 1-28 daily
| Study group | Role | What they receive |
|---|---|---|
| everolimus/lapatinib | Experimental | Part 1, dose finding: everolimus and lapatinib at assigned dose daily Part 2, cohort A: Everolimus MTD from Part I: 5 mg PO 1-28 Daily Lapatinib MTD from Part I: 1,250 mg PO Cycle 1, Daily Days 8-28 Subsequent Cycles, Days 1-28 Part 2, cohort B: Lapatinib MTD from Part I: 1,250 mg PO 1-28 Daily Everolimus MTD from Part I: 5 mg PO Cycle 1, Daily Days 8-28 Subsequent Cycles, Days 1-28 Receives: Drug: everolimus; Drug: lapatinib ditosylate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose of lapatinib and everolimus (Part I)
Measured: 1 month
Secondary outcomes (1)
Pharmacokinetics (Part II)
Measured: 1 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jul 2006 (estimated)
- Study startSep 2006
- Primary completionAug 2007
- Study completionSep 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for LymphomaStudies of the same condition, open and under way.
- More trials run by SWOG Cancer Research NetworkThe 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
- 66 participants (actual)
Sponsor and investigators
- Lead sponsor
- SWOG Cancer Research Network
- Sponsor type
- Research network
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Shirish M. Gadgeel, MD, Study chair, Barbara Ann Karmanos Cancer InstitutePatricia M. LoRusso, DO, Principal investigator, Barbara Ann Karmanos Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00352443
- Sponsor's protocol ID
- S0528
- Other IDs
- U10CA032102, S0528
- Status last verified
- Mar 2015
- First submitted
- 13 Jul 2006
- Last updated
- 6 Mar 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Hoban CJ, Hoering A, Synold TW, et al.: Phase I evaluation of lapatinib and everolimus in patients with advanced malignancies: Southwest Oncology Group trial S0528. [Abstract] J Clin Oncol 27 (Suppl 15): A-3553, 2009.
Gadgeel SM, Lew DL, Synold TW, LoRusso P, Chung V, Christensen SD, Smith DC, Kingsbury L, Hoering A, Kurzrock R. Phase I study evaluating the combination of lapatinib (a Her2/Neu and EGFR inhibitor) and everolimus (an mTOR inhibitor) in patients with advanced cancers: South West Oncology Group (SWOG) Study S0528. Cancer Chemother Pharmacol. 2013 Nov;72(5):1089-96. doi: 10.1007/s00280-013-2297-4. Epub 2013 Sep 22.
PubMed 24057042
Study at a glance
From the registry record, last updated by the sponsor on 6 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study Evaluating the Combination of Lapatinib (GW572016; NSC-727989) and Everolimus (RAD001) in Patients With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT00352443
- Acronym / sponsor ID
- S0528
- Keywords
- adult grade III lymphomatoid granulomatosis, recurrent adult grade III lymphomatoid granulomatosis, Waldenstrom macroglobulinemia, recurrent adult Burkitt lymphoma, stage IV adult Burkitt lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse small cleaved cell lymphoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 66 participants (actual)
- Lead sponsor
- SWOG Cancer Research NetworkResearch network
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Sep 2006
- Primary completion
- Aug 2007 (actual)
- Study completion
- Sep 2013 (actual)
- First posted
- 14 Jul 2006 (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.
RATIONALE: Lapatinib and everolimus may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Everolimus may also stop the growth of cancer cells by blocking blood flow to the cancer. Giving lapatinib together with everolimus may kill more cancer cells.
PURPOSE: This phase I trial is studying the side effects and best dose of lapatinib and everolimus in treating patients with advanced solid tumors or non-Hodgkin's lymphoma.
Detailed description
OBJECTIVES:
- Estimate the maximum tolerated dose (MTD) of lapatinib and everolimus in patients with advanced solid tumors or non-Hodgkin's lymphoma. (Part I)
- Investigate the pharmacokinetics of everolimus and lapatinib (when given alone and in combination) at the MTD determined in Part I. (Part II)
- Investigate the effects of everolimus and lapatinib (when given alone and in combination) on serum levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), matrix metalloproteinase (MMP)-2 and MMP-9, interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α). (Part II)
OUTLINE: This is a multicenter, dose-escalation study followed by a randomized study. Initial patients enrolled on the study are treated in part I. After the maximum tolerated dose (MTD) is determined in part I, subsequent patients are enrolled and treated in part II.
- Part I: Patients receive oral everolimus and oral lapatinib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of everolimus and lapatinib until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.
- Part II: Patients are randomized to 1 of 2 treatment arms. Everolimus and lapatinib are administered at the MTD determined in part I.
- Arm I: Patients receive oral everolimus once daily on days 1-28. Patients also receive oral lapatinib once daily on days 8-28 during the first course and on days 1-28 during all subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
- Arm II: Patients receive oral lapatinib once daily on days 1-28. Patients also receive oral everolimus once daily on days 8-28 during the first course and on days 1-28 during all subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients in part II undergo blood collection periodically for correlative biomarker and pharmacokinetic studies.
After finishing treatment, patients are followed periodically for 28 days.
PROJECTED ACCRUAL: A total of 48 patients will be accrued for this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| everolimus/lapatinib | Experimental | Drug: everolimus, Drug: lapatinib ditosylatePart 1, dose finding: everolimus and lapatinib at assigned dose daily Part 2, cohort A: Everolimus MTD from Part I: 5 mg PO 1-28 Daily Lapatinib MTD from Part I: 1,250 mg PO Cycle 1, Daily Days 8-28 Subsequent Cycles, Days 1-28 Part 2, cohort B: Lapatinib MTD from Part I: 1,250 mg PO 1-28 Daily Everolimus MTD from Part I: 5 mg PO Cycle 1, Daily Days 8-28 Subsequent Cycles, Days 1-28 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| everolimuspart 1: dose assigned by ETx online system PO days 1-28 daily part 2: cohort a: 5 mg PO days 1-28 part 2: cohort a: 1250 mg PO days 8-28 (cycle 1) days 1-28 (subsequent cycles) | Drug | everolimus/lapatinib |
| lapatinib ditosylatedose assigned by ETx online system PO days 1-28 daily part 2 cohort a: 1250 mg PO d 8-28 (cycle 1) days 1-28 (subsequent cycles) part 2 cohort b: 120 mg PO days 1-28 daily | Drug | everolimus/lapatinib |
Primary outcome
Maximum tolerated dose of lapatinib and everolimus (Part I)
Time frame: 1 month
1 secondary outcome
Pharmacokinetics (Part II)
Time frame: 1 month
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 6 Mar 2015.
- Results publicationHoban CJ, Hoering A, Synold TW, et al.: Phase I evaluation of lapatinib and everolimus in patients with advanced malignancies: Southwest Oncology Group trial S0528. [Abstract] J Clin Oncol 27 (Suppl 15): A-3553, 2009.
- Derived from this study: PubMed 24057042Gadgeel SM, Lew DL, Synold TW, LoRusso P, Chung V, Christensen SD, Smith DC, Kingsbury L, Hoering A, Kurzrock R. Phase I study evaluating the combination of lapatinib (a Her2/Neu and EGFR inhibitor) and everolimus (an mTOR inhibitor) in patients with advanced cancers: South West Oncology Group (SWOG) Study S0528. Cancer Chemother Pharmacol. 2013 Nov;72(5):1089-96. doi: 10.1007/s00280-013-2297-4. Epub 2013 Sep 22.
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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.
Shirish M. Gadgeel, MD study chair
Barbara Ann Karmanos Cancer Institute
Patricia M. LoRusso, DO principal investigator
Barbara Ann Karmanos Cancer Institute
6 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 everolimus and lapatinib ditosylate in people with Lymphoma and Unspecified Adult Solid Tumor, Protocol Specific, run by SWOG Cancer Research Network at 6 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?
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 6 Mar 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 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 of lapatinib and everolimus (Part I) (time frame: 1 month). 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 NCT00352443, which also lists 2 linked publications.
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 6 Mar 2015; AzTrials last refreshed its copy on 7 Nov 2026.