Clinical trial NCT00073008: A Study Of Oral GW572016 In Advanced Or Metastatic Non-Small Cell Lung Cancer
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Lung Cancer, Non-Small Cell
Keywords: EGFR
ErbB1
ErbB2
metastatic
lapatinib
Her-2/neu
protein kinase inhibitor
BAC
GW572016
Advanced
NSCLC
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2003-11-17
Enrollment: 131
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.


Eligibility 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;
* 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.

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.

Primary outcomes:
measure: Tumor Response in the Targeted Population Through the End of Treatment
timeFrame: Baseline and then every 8 weeks through end of treatment
Secondary outcomes:
measure: Progression-free Survival (PFS) at Four Months in the Targeted Population
timeFrame: From randomization and then every 8 weeks up to four months
measure: Progression-free Survival (PFS) at Four Months in the Non-Targeted Population
timeFrame: From randomization and then every 8 weeks up to four months
measure: 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
measure: 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
measure: Pharmacogenetics (PgX)
timeFrame: From randomization at every 4-week assessment through end of treatment
measure: Quality of Life
timeFrame: Baseline and then every 4 weeks through end of treatment
measure: Time to Response
timeFrame: From randomization and then every 8 weeks to time of response to study drug
measure: Duration of Response
timeFrame: Time from first documented evidence of response to study treatment and then every 8 weeks until disease progression or death
measure: Time to Tumor Progression
timeFrame: From randomization and then every 8 weeks to disease progression or death
measure: Overall Survival
timeFrame: From randomization and then every 8 weeks while on study drug and then every 3 months as follow-up until death
measure: Review of Non-small Cell Lung Cancer (NSCLC) Histology (Cell Type) Using an Independent Review
timeFrame: Anytime from Baseline through end of study
Other outcomes:
measure: Tumor Response in the Non-Targeted Population Through the End of Treatment
timeFrame: Baseline and then every 8 weeks through end of treatment
Locations:
city: Jasper
country: United States
facility: GSK Investigational Site
state: Alabama
city: Greenbrae
country: United States
facility: GSK Investigational Site
state: California
city: La Jolla
country: United States
facility: GSK Investigational Site
state: California
city: Long Beach
country: United States
facility: GSK Investigational Site
state: California
city: Poway
country: United States
facility: GSK Investigational Site
state: California
city: Rancho Mirage
country: United States
facility: GSK Investigational Site
state: California
city: Washington
country: United States
facility: GSK Investigational Site
state: District of Columbia
city: Gainsville
country: United States
facility: GSK Investigational Site
state: Florida
city: Elk Grove Village
country: United States
facility: GSK Investigational Site
state: Illinois
city: Houma
country: United States
facility: GSK Investigational Site
state: Louisiana
city: Metairie
country: United States
facility: GSK Investigational Site
state: Louisiana
city: Lebanon
country: United States
facility: GSK Investigational Site
state: New Hampshire
city: New Brunswick
country: United States
facility: GSK Investigational Site
state: New Jersey
city: Santa Fe
country: United States
facility: GSK Investigational Site
state: New Mexico
city: Nyack
country: United States
facility: GSK Investigational Site
state: New York
city: Chapel Hill
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Durham
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Cleveland
country: United States
facility: GSK Investigational Site
state: Ohio
city: Portland
country: United States
facility: GSK Investigational Site
state: Oregon
city: Philadelphia
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Nashville
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Corpus Christi
country: United States
facility: GSK Investigational Site
state: Texas
city: Houston
country: United States
facility: GSK Investigational Site
state: Texas
city: Calgary
country: Canada
facility: GSK Investigational Site
state: Alberta
city: Edmonton
country: Canada
facility: GSK Investigational Site
state: Alberta
city: Kingston
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Kitchener
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Ottawa
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Greenfield Park
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Levis
country: Canada
facility: GSK Investigational Site
state: Quebec
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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;
citation: 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.