S0528 Lapatinib and Everolimus in Treating Patients With Advanced Solid Tumors or Non-Hodgkin's Lymphoma

March 5, 2015 updated by: Southwest Oncology Group

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

66

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90089-9181
        • USC/Norris Comprehensive Cancer Center and Hospital
      • Sacramento, California, United States, 95817
        • University of California Davis Cancer Center
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado Cancer Center at UC Health Sciences Center
    • Kentucky
      • Lexington, Kentucky, United States, 40536-0093
        • Lucille P. Markey Cancer Center at University of Kentucky
    • Michigan
      • Ann Arbor, Michigan, United States, 48109-0942
        • University Of Michigan Comprehensive Cancer Center
    • Washington
      • Seattle, Washington, United States, 98195-6043
        • University Cancer Center at University of Washington Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: everolimus/lapatinib
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: everolimus
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)
Drug: lapatinib ditosylate
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Maximum tolerated dose of lapatinib and everolimus (Part I)
Time Frame: 1 month
1 month

Secondary Outcome Measures

Outcome Measure
Time Frame
Pharmacokinetics (Part II)
Time Frame: 1 month
1 month

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Southwest Oncology Group

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Patricia M. LoRusso, DO, Barbara Ann Karmanos Cancer Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2006

Primary Completion (Actual)

August 1, 2007

Study Completion (Actual)

September 1, 2013

Study Registration Dates

First Submitted

July 13, 2006

First Submitted That Met QC Criteria

July 13, 2006

First Posted (Estimate)

July 14, 2006

Study Record Updates

Last Update Posted (Estimate)

March 6, 2015

Last Update Submitted That Met QC Criteria

March 5, 2015

Last Verified

March 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • S0528 (Other Identifier: SWOG)
  • U10CA032102 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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