Last updated: 11/04/2018 06:34:20
A Study Of Oral GW572016 In Advanced Or Metastatic Non-Small Cell Lung Cancer
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Terminated (halted prematurely)
Terminated (halted prematurely)
Trial overview
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
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Single Group Assignment
Masking:
None (Open Label)
Allocation:
Randomized
Primary outcomes:
Tumor response in the Targeted Population through the end of treatment
Timeframe: Baseline and then every 8 weeks through end of treatment
Secondary outcomes:
Progression-free survival (PFS) at four months in the Targeted Population
Timeframe: From randomization and then every 8 weeks up to four months
Progression-free survival (PFS) at four months in the Non-Targeted Population
Timeframe: From randomization and then every 8 weeks up to four months
The number of participants who showed certain biomarkers in their serum or tumor tissue
Timeframe: From randomization to disease progression (for serum biomarkers) or until analyses of tumor tissue samples
Pharmacokinetics (PK) of lapatinib
Timeframe: From randomization to time of PK period completed: Day 1 (first dose) and Days 2, 28, and 29 while participant was on study drug
Pharmacogenetics (PgX)
Timeframe: From randomization at every 4-week assessment through end of treatment
Quality of life
Timeframe: Baseline and then every 4 weeks through end of treatment
Time to response
Timeframe: From randomization and then every 8 weeks to time of response to study drug
Duration of response
Timeframe: Time from first documented evidence of response to study treatment and then every 8 weeks until disease progression or death
Time to tumor progression
Timeframe: From randomization and then every 8 weeks to disease progression or death
Overall survival
Timeframe: From randomization and then every 8 weeks while on study drug and then every 3 months as follow-up until death
Review of non-small cell lung cancer (NSCLC) histology (cell type) using an independent review
Timeframe: Anytime from Baseline through end of study
Interventions:
Drug: GW572016 (lapatinib)
Enrollment:
131
Observational study model:
Not applicable
Primary completion date:
2008-28-07
Time perspective:
Not applicable
Clinical 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;16(6):1938-1949.
Medical condition
Lung Cancer, Non-Small Cell
Product
lapatinib
Collaborators
Not applicable
Study date(s)
November 2003 to July 2008
Type
Interventional
Phase
2
Participation criteria
Sex
Female & Male
Age
18+ years
Accepts healthy volunteers
No
- 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,
- 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;
Inclusion and exclusion criteria
Inclusion criteria:
- 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;
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1;
- Life expectancy of ≥ 12 weeks;
- ≥ 18 years old;
- 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.
A female is eligible to enter and participate in this study if she is of:
Exclusion criteria:
- 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;
- 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 location(s)
Location
GSK Investigational Site
Gainsville, Florida, United States, 32610
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Elk Grove Village, Illinois, United States, 60007
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Durham, North Carolina, United States, 27707
Status
Study Complete
Location
GSK Investigational Site
Houma, Louisiana, United States, 70360
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Philadelphia, Pennsylvania, United States, 19140
Status
Study Complete
Location
GSK Investigational Site
Metairie, Louisiana, United States, 70006
Status
Study Complete
Location
GSK Investigational Site
Washington, District of Columbia, United States, 20007
Status
Study Complete
Location
GSK Investigational Site
Santa Fe, New Mexico, United States, 87505
Status
Study Complete
Location
GSK Investigational Site
Long Beach, California, United States, 90813
Status
Study Complete
Location
GSK Investigational Site
Greenfield Park, Québec, Canada, J4V 2H1
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Nyack, New York, United States, 10960
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Poway, California, United States, 92064
Status
Study Complete
Location
GSK Investigational Site
La Jolla, California, United States, 92037
Status
Study Complete
Location
GSK Investigational Site
Corpus Christi, Texas, United States, 78412
Status
Study Complete
Location
GSK Investigational Site
Greenbrae, California, United States, 94904-2007
Status
Study Complete
Location
GSK Investigational Site
New Brunswick, New Jersey, United States, 08901
Status
Study Complete
Location
GSK Investigational Site
Portland, Oregon, United States, 97213
Status
Study Complete
Location
GSK Investigational Site
Chapel Hill, North Carolina, United States, 27599-7600
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Rancho Mirage, California, United States, 92270
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Lebanon, New Hampshire, United States, 03756
Status
Study Complete
Location
GSK Investigational Site
Nashville, Tennessee, United States, 37203
Status
Study Complete
Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Terminated (halted prematurely)
Actual primary completion date
2008-28-07
Actual study completion date
2008-28-07
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
Additional information
Not applicable
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