NCT00352443

Brief 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. 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
66

participants targeted

Target at P75+ for phase_1 lymphoma

Timeline
Completed

Started Sep 2006

Longer than P75 for phase_1 lymphoma

Geographic Reach
1 country

6 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 13, 2006

Completed
1 day until next milestone

First Posted

Study publicly available on registry

July 14, 2006

Completed
2 months until next milestone

Study Start

First participant enrolled

September 1, 2006

Completed
11 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2007

Completed
6.1 years until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2013

Completed
Last Updated

March 6, 2015

Status Verified

March 1, 2015

Enrollment Period

11 months

First QC Date

July 13, 2006

Last Update Submit

March 5, 2015

Conditions

LymphomaUnspecified Adult Solid Tumor, Protocol Specific

Keywords

adult grade III lymphomatoid granulomatosisrecurrent adult grade III lymphomatoid granulomatosisWaldenstrom macroglobulinemiarecurrent adult Burkitt lymphomastage IV adult Burkitt lymphomarecurrent adult diffuse large cell lymphomarecurrent adult diffuse mixed cell lymphomarecurrent adult diffuse small cleaved cell lymphomarecurrent adult immunoblastic large cell lymphomarecurrent adult lymphoblastic lymphomarecurrent grade 1 follicular lymphomarecurrent grade 2 follicular lymphomarecurrent grade 3 follicular lymphomarecurrent mantle cell lymphomarecurrent marginal zone lymphomarecurrent small lymphocytic lymphomastage IV adult diffuse large cell lymphomastage IV adult diffuse mixed cell lymphomastage IV adult diffuse small cleaved cell lymphomastage IV adult immunoblastic large cell lymphomastage IV adult lymphoblastic lymphomastage IV grade 1 follicular lymphomastage IV grade 2 follicular lymphomastage IV grade 3 follicular lymphomastage IV mantle cell lymphomastage IV marginal zone lymphomastage IV small lymphocytic lymphomaextranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissuenodal marginal zone B-cell lymphomasplenic marginal zone lymphomaunspecified adult solid tumor, protocol specificanaplastic large cell lymphomaangioimmunoblastic T-cell lymphomaadult nasal type extranodal NK/T-cell lymphoma

Outcome Measures

Primary Outcomes (1)

  • Maximum tolerated dose of lapatinib and everolimus (Part I)

    1 month

Secondary Outcomes (1)

  • Pharmacokinetics (Part II)

    1 month

Study Arms (1)

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

Drug: everolimusDrug: lapatinib ditosylate

Interventions

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)

everolimus/lapatinib
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

everolimus/lapatinib

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

Study Sites (6)

USC/Norris Comprehensive Cancer Center and Hospital

Los Angeles, California, 90089-9181, United States

Location

University of California Davis Cancer Center

Sacramento, California, 95817, United States

Location

University of Colorado Cancer Center at UC Health Sciences Center

Aurora, Colorado, 80045, United States

Location

Lucille P. Markey Cancer Center at University of Kentucky

Lexington, Kentucky, 40536-0093, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109-0942, United States

Location

University Cancer Center at University of Washington Medical Center

Seattle, Washington, 98195-6043, United States

Location

Related Publications (2)

  • 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.

    RESULT

  • 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.

    PMID: 24057042DERIVED

MeSH Terms

Conditions

LymphomaWaldenstrom MacroglobulinemiaBurkitt LymphomaLymphoma, Large B-Cell, DiffuseLymphoma, Non-HodgkinLymphoma, Large-Cell, ImmunoblasticPrecursor Cell Lymphoblastic Leukemia-LymphomaLymphoma, FollicularLymphoma, Mantle-CellLymphoma, B-Cell, Marginal ZoneLeukemia, Lymphocytic, Chronic, B-CellLymphoma, Large-Cell, AnaplasticImmunoblastic LymphadenopathyLymphoma, Extranodal NK-T-Cell

Interventions

EverolimusLapatinib

Condition Hierarchy (Ancestors)

Neoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesNeoplasms, Plasma CellHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHematologic DiseasesHemorrhagic DisordersEpstein-Barr Virus InfectionsHerpesviridae InfectionsDNA Virus InfectionsVirus DiseasesInfectionsTumor Virus InfectionsLymphoma, B-CellLeukemia, LymphoidLeukemiaLeukemia, B-CellChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and SymptomsLymphoma, T-CellLymphadenopathy

Intervention Hierarchy (Ancestors)

SirolimusMacrolidesLactonesOrganic ChemicalsQuinazolinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic Compounds

Study Officials

  • Shirish M. Gadgeel, MD

    Barbara Ann Karmanos Cancer Institute

    STUDY CHAIR

  • Patricia M. LoRusso, DO

    Barbara Ann Karmanos Cancer Institute

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
NETWORK
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 13, 2006

First Posted

July 14, 2006

Study Start

September 1, 2006

Primary Completion

August 1, 2007

Study Completion

September 1, 2013

Last Updated

March 6, 2015

Record last verified: 2015-03

Locations

US(6)