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Lung Cancer, Non-Small CellPhase 2NCT00073008

A Study Of Oral GW572016 In Advanced Or Metastatic Non-Small Cell Lung Cancer

A Phase 2 study testing GW572016 (lapatinib) in people with Lung Cancer, Non-Small Cell, run by GlaxoSmithKline at 31 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This study was designed to evaluate and compare the efficacy of two dose schedules of an oral investigational drug for the treatment of advanced or metastatic non-small cell lung cancer. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Lung Cancer, Non-Small Cell
What is being tested?
GW572016 (lapatinib)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
131 participants
Where
31 sitesin 2 countries
Study dates
Nov 2003to Jul 2008
Phase
Phase 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

  • Signed informed consent;
  • Subjects must have histologically confirmed advanced (incurable stage IIIB or IV according to the International Staging System, [Mountain, 1997] Non-Small Cell Lung Cancer (NSCLC) at primary diagnosis or relapsed after curative-intent surgery. Only patients with either (1) the histological subtypes of adenocarcinoma with BAC (Bronchioloalveolar) features or pure BAC (as defined by the 1999 World Health Organization criteria) or, (2) never smokers (i.e. smoked <100 cigarettes in lifetime) with any histology of NSCLC (squamous, adenocarcinoma, lifetime) with any histology of NSCLC (squamous, adenocarcinoma,
  • Patients can have had a maximum of 1 prior systemic therapy (chemotherapy or biologic therapy) for NSCLC that ended at least 3 weeks prior to enrollment. Patients that have had adjuvant cytotoxic chemotherapy that ended at least 3 months prior to enrollment are eligible. Prior surgery and radiotherapy are permitted. Patients should recover from acute side effects of radiation before enrollment (3-4 weeks). Concurrent radiotherapy is prohibited;
  • Archived tumor tissue available for evaluation of genetic and intra-tumoral protein or mRNA expression levels of relevant biomarkers. A minimum of 10 slides of archived tumor tissue is required; however, 15 slides should be sent, if available. For patients diagnosed on the basis of pleural effusions, efforts should be made to provide as many slides as possible made with cells obtained from pleural aspirates. Results of biomarkers will not be used to determine subject eligibility for the study;
  • Measurable lesion(s) according to RECIST (e.g., ≥15 mm with conventional techniques (medical photograph [skin or oral lesion], palpation, plain X-ray, CT, MRI, or ≥10 mm with spiral CT scan);
  • At least 1 measurable lesion located outside of the prior radiation field or, if located within the prior field of irradiation, is increasing in size;
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  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1;
  • Life expectancy of ≥ 12 weeks;
  • ≥ 18 years old;
  • A female is eligible to enter and participate in this study if she is of: • Non-childbearing potential (i.e., women with functioning ovaries who have a current documented tubal ligation, women who had a hysterectomy, women who are post-menopausal, or women who have had both ovaries surgically removed); or • Childbearing potential (i.e., women with functioning ovaries and no documented impairment of oviductal or uterine function that would cause sterility). This category includes women with oligomenorrhea (even severe), women who are perimenopausal, and young women who have begun to menstruate. Women of childbearing potential must have a negative serum pregnancy test at screening, and agree to 1 of the following: a Complete abstinence from intercourse from 2 weeks prior to administration of the first dose of GW572016 until 28 days after the final dose of GW572016; or b Consistent and correct use of 1 of the following acceptable methods of birth control: 1. Male partner who is sterile prior to the female subject's entry into the study and is the sole sexual partner for that female subject; or 2. Implants of levonorgestrel 3. Injectable progestogen 4. Any intrauterine device (IUD) with a documented failure rate of less than 1% per year; or 5. Oral contraceptives (either combined or Progestogen only) 6. Barrier methods including diaphragm or condom with a spermicide
  • Able to swallow and retain oral medication;
  • Cardiac ejection fraction within the institutional range of normal as measured by echocardiogram. Subjects with known history of uncontrolled or symptomatic echocardiogram. Subjects with known history of uncontrolled or symptomatic angina, arrhythmias, or congestive heart failure are not eligible;
  • Have adequate organ function as defined in Table 1 Baseline Laboratory Values for Inclusion;
  • Subjects must complete all screening assessments as outlined in the protocol.

Who cannot join

  • Malabsorption Syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel. Subjects with ulcerative colitis are also excluded;
  • History of other malignancy. Subjects who have been disease-free for 5 years, or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible;
  • Concurrent disease or condition that would make the subject inappropriate for study participation, or any serious medical disorder that would interfere with the subject's safety;
  • Unresolved or unstable, serious toxicity from prior administration of another investigational drug;
  • Active or uncontrolled infection;
  • Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent;
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  • Uncontrolled angina, arrhythmias, or congestive heart failure. Patients whose symptoms are under control are eligible.
  • Known history of or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis except for individuals who have previously treated CNS metastases, are asymptomatic, and have had no requirement for steroids or antiseizure medication for ≥ 3 months prior to study enrollment. Routine screening with CNS imaging studies (computed tomography [CT] or magnetic resonance imaging [MRI]) is required only if clinically indicated or if the subject has a history of CNS metastases;
  • Concurrent cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, biologic therapy, hormonal therapy, and tumor embolization).
  • Concurrent treatment with an investigational agent or participation in another clinical trial
  • Use of an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of GW572016;
  • Prior therapy with any ErbB1 and/or ErbB2 inhibitor;
  • The subject has a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to GW572016.
  • Has taken/received the following inhibitors of CYP3A4 within the specified number of days prior to the first dose of study medication: Seven (7) days: antibiotics (clarithromycin, erythromycin, troleandomycin), antiretrovirals (delavirdine), protease inhibitors (ritonavir, indinavir, saquinavir, nelfinavir, amprenavir, lopinavir), systemic antifungals (itraconazole, ketoconazole, voriconazole, fluconazole (doses of 200 mg/day and above)), antidepressants (nefazodone, fluovoxamine), calcium channel blockers (verapamil, diltiazem), gastrointestinal (cimetidine, aprepitant), and grapefruit or its juice. Six (6) months: amiodarone.
  • Has taken/received the following inducers of CYP3A4 within fourteen (14) days prior to the first dose of study medication: glucocorticoids (dexamethasone or dexamethasone equivalent dose > 1.5mg/day (see chart in Section 7.2 for conversion), anticonvulsants (phenytoin, carbamazepine, phenobarbital), efavirenz, nevirapine, antibiotics (rifampin (rifampicin), rifabutin, rifapentine), St. John's Wort and modafinil.

Trial locations and contacts

31 sites in 2 countries.

31 sites in 2 countries

United States23 sites
  • GSK Investigational Site

    Chapel Hill, North Carolina, 27599-7600

  • GSK Investigational Site

    Cleveland, Ohio, 44106

  • GSK Investigational Site

    Corpus Christi, Texas, 78412

  • GSK Investigational Site

    Durham, North Carolina, 27707

  • GSK Investigational Site

    Elk Grove Village, Illinois, 60007

  • GSK Investigational Site

    Gainsville, Florida, 32610

  • GSK Investigational Site

    Greenbrae, California, 94904-2007

  • GSK Investigational Site

    Houma, Louisiana, 70360

  • GSK Investigational Site

    Houston, Texas, 77030

  • GSK Investigational Site

    Jasper, Alabama, 35501

  • GSK Investigational Site

    La Jolla, California, 92037

  • GSK Investigational Site

    Lebanon, New Hampshire, 03756

  • GSK Investigational Site

    Long Beach, California, 90813

  • GSK Investigational Site

    Metairie, Louisiana, 70006

  • GSK Investigational Site

    Nashville, Tennessee, 37203

  • GSK Investigational Site

    New Brunswick, New Jersey, 08901

  • GSK Investigational Site

    Nyack, New York, 10960

  • GSK Investigational Site

    Philadelphia, Pennsylvania, 19140

  • GSK Investigational Site

    Portland, Oregon, 97213

  • GSK Investigational Site

    Poway, California, 92064

  • GSK Investigational Site

    Rancho Mirage, California, 92270

  • GSK Investigational Site

    Santa Fe, New Mexico, 87505

  • GSK Investigational Site

    Washington D.C., District of Columbia, 20007

Other trials in United States

Canada8 sites
  • GSK Investigational Site

    Calgary, Alberta, T2N 4N2

  • GSK Investigational Site

    Edmonton, Alberta, T6G 1Z2

  • GSK Investigational Site

    Greenfield Park, Quebec, J4V 2H1

  • GSK Investigational Site

    Kingston, Ontario, K7L 5P9

  • GSK Investigational Site

    Kitchener, Ontario, N2G 1G3

  • GSK Investigational Site

    Lévis, Quebec, G6V 3Z1

  • GSK Investigational Site

    Ottawa, Ontario, K1H 1C4

  • GSK Investigational Site

    Toronto, Ontario, M5G 2M9

Other trials in Canada

About this study

Official title: A Phase 2 Multicenter Trial Comparing Two Schedules of GW572016 as First or Second Line Monotherapy in Subjects With Advanced or Metastatic Non-Small Cell Lung Cancer With Either Bronchioloalveolar Carcinoma or No Smoking History

This study was designed to evaluate and compare the efficacy of two dose schedules of an oral investigational drug for the treatment of advanced or metastatic non-small cell lung cancer.

Being tested
GW572016 (lapatinib)
Keywords
EGFR, ErbB1, ErbB2, metastatic, lapatinib, Her-2/neu, protein kinase inhibitor, BAC, GW572016, Advanced, NSCLC
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Neoplasm Metastasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GW572016 (lapatinib)Drug

    tyrosine kinase inhibitor

Study groups in NCT00073008
Study groupRoleWhat they receive
lapatinibOtherRandomized, open-label, parallel group, 2-stage study to evaluate and compare 2 dose schedules (1500 mg once daily and 500 mg twice daily) of oral lapatinib.
Receives: Drug: GW572016 (lapatinib)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Tumor Response in the Targeted Population Through the End of Treatment

    Disease progression and tumor response (number of participants achieving a complete response [CR] or partial response [PR]), using standardized criteria (Response evaluation criteria in solid tumors). CR, disappearance of all target lesions; PR, 30% decrease in the sum of the longest diameter of target lesions; progressive disease, 20% increase in the sum of the longest diameter of target lesions; stable disease, small changes that do not meet above criteria. Disease assessment was done at baseline and then every 8 weeks after starting treatment, until the participant discontinued treatment.

    Measured: Baseline and then every 8 weeks through end of treatment

Secondary outcomes (11)
  1. Progression-free Survival (PFS) at Four Months in the Targeted Population

    Percentage of participants in the Targeted Population, at 4 months after starting study drug, who were alive and without disease progression.

    Measured: From randomization and then every 8 weeks up to four months

  2. Progression-free Survival (PFS) at Four Months in the Non-Targeted Population

    Percentage of participants in the Non-Targeted Population, at 4 months after starting study drug, who were alive and without disease progression.

    Measured: From randomization and then every 8 weeks up to four months

  3. The Number of Participants Who Showed Certain Biomarkers in Their Serum or Tumor Tissue

    To further characterize the participant population, these biomarkers could be tested: serum levels of ErbB1 and ErbB2; intra-tumoral expression of ErbB1, ErbB2, etc.; mutations in ErbB1, ErbB2, and k-ras. Based on the interim analysis at the end of Stage 1, and predefined stopping rules for futility, further enrollment into the study was stopped due to lack of efficacy on both treatment arms; therefore, serum biomarkers were not analyzed.

    Measured: From randomization to disease progression (for serum biomarkers) or until analyses of tumor tissue samples

  4. Pharmacokinetics (PK) of Lapatinib

    To characterize the PK (absorption, distribution, metabolism, and excretion) of the study drug lapatinib in the participant population. PK is defined as the concentration of drug in a participant's blood at certain time points after the drug was taken by mouth. Based on the interim analysis at the end of Stage 1, and predefined stopping rules for futility, further enrollment into the study was stopped due to lack of efficacy on both treatment arms; therefore, pharmacokinetics were not analyzed.

    Measured: From randomization to time of PK period completed: Day 1 (first dose) and Days 2, 28, and 29 while participant was on study drug

  5. Pharmacogenetics (PgX)

    To (1) investigate the relationship between genetic variants in specific genes and the absorption, distribution, metabolism, and excretion (pharmacokinetics) of lapatinib, and to (2) investigate the relationship between genetic variants in select genes in DNA and the response (safety, efficacy, and tolerability) to lapatinib. Based on the interim analysis at the end of Stage 1, and predefined stopping rules for futility, further enrollment into the study was stopped due to lack of efficacy on both treatment arms; therefore, pharmacogenetics were not analyzed.

    Measured: From randomization at every 4-week assessment through end of treatment

  6. Quality of Life

    Standard survey forms were completed by the participant at scheduled assessments to find out how the participant felt while on study. Based on the interim analysis at the end of Stage 1, and predefined stopping rules for futility, further enrollment into the study was stopped due to lack of efficacy on both treatment arms; therefore, quality of life was not analyzed.

    Measured: Baseline and then every 4 weeks through end of treatment

  7. Time to Response

    Time from randomization until first documented evidence of partial or complete tumor response, measured using standard criteria (RECIST). Based on the interim analysis at the end of Stage 1, and predefined stopping rules for futility, further enrollment into the study was stopped due to lack of efficacy on both treatment arms; therefore, time to response was not analyzed.

    Measured: From randomization and then every 8 weeks to time of response to study drug

  8. Duration of Response

    For those participants who show a complete or partial response, duration of response would be time from first documented evidence of response (complete or partial response by RECIST) until disease progression or death, if sooner. Based on the interim analysis at the end of Stage 1, and predefined stopping rules for futility, further enrollment into the study was stopped due to lack of efficacy on both treatment arms; therefore, duration of response was not analyzed.

    Measured: Time from first documented evidence of response to study treatment and then every 8 weeks until disease progression or death

  9. Time to Tumor Progression

    Time from randomization until the first documented sign of disease progression or death due to any cause, if sooner. Based on the interim analysis at the end of Stage 1, and predefined stopping rules for futility, further enrollment into the study was stopped due to lack of efficacy on both treatment arms; therefore, time to tumor progression was not analyzed.

    Measured: From randomization and then every 8 weeks to disease progression or death

  10. Overall Survival

    Overall survival is measured as the time from randomization until death due to any cause. Based on the interim analysis at the end of Stage 1, and predefined stopping rules for futility, further enrollment into the study was stopped due to lack of efficacy on both treatment arms; therefore, overall survival was not analyzed.

    Measured: From randomization and then every 8 weeks while on study drug and then every 3 months as follow-up until death

  11. Review of Non-small Cell Lung Cancer (NSCLC) Histology (Cell Type) Using an Independent Review

    Comparison of the specific cell type (histology) of non-small cell lung cancer from participant's tissue samples, as determined by local pathologist, to the type determined by an independent pathologist. Based on the interim analysis at the end of Stage 1, and predefined stopping rules for futility, further enrollment into the study was stopped due to lack of efficacy on both treatment arms; therefore, NSCLC histology was not analyzed.

    Measured: Anytime from Baseline through end of study

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Nov 2003 (estimated)
  2. Study startNov 2003
  3. Primary completionJul 2008
  4. Study completionJul 2008

Why it stopped: Based on interim analysis at the end of Stage 1, and predefined stopping rules for futility, further enrollment was stopped due to lack of efficacy

Resources

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
131 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00073008
Sponsor's protocol ID
EGF20014
Status last verified
Jan 2017
First submitted
13 Nov 2003
Last updated
28 Feb 2017
Data monitoring committee
Yes

Publications

  • Colin F Spraggs, Laura R Parham, Christine M. Hunt and Colin T Dollery. Characterisation of lapatinib-associated DILI cases by Class II HLA and UGT1A1*28 genotypes. [Clin Pharmacol Ther]. 2012;

  • Ross HJ, Blumenschein GR Jr, Aisner J, Damjanov N, Dowlati A, Garst J, Rigas JR, Smylie M, Hassani H, Allen KE, Leopold L, Zaks TZ, Shepherd FA. Randomized phase II multicenter trial of two schedules of lapatinib as first- or second-line monotherapy in patients with advanced or metastatic non-small cell lung cancer. Clin Cancer Res. 2010 Mar 15;16(6):1938-49. doi: 10.1158/1078-0432.CCR-08-3328. Epub 2010 Mar 9.

    PubMed 20215545

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing GW572016 (lapatinib) in people with Lung Cancer, Non-Small Cell, run by GlaxoSmithKline at 31 sites in 2 countries.

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 14 inclusion and 15 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 28 Feb 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 31 sites in United States, Canada. 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 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 6 Jan 2010). 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?

Tumor Response in the Targeted Population Through the End of Treatment (time frame: Baseline and then every 8 weeks through end of treatment). 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 NCT00073008, 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 28 Feb 2017.

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