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

NCT00073008 | Terminated Phase 2 Results DMC

• 1 other identifier: EGF20014
• Study Type: interventional
• Target: 131
• Locations: 2 countries
• Sites: 31

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.

Conditions

Lung Cancer, Non-Small Cell

Keywords

EGFR; ErbB1; ErbB2; metastatic; lapatinib; Her-2/neu; protein kinase inhibitor; BAC; GW572016; Advanced; NSCLC

Outcome Measures

Primary Outcomes (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.

  Baseline and then every 8 weeks through end of treatment

Secondary Outcomes (11)

• Progression-free Survival (PFS) at Four Months in the Targeted Population

  From randomization and then every 8 weeks up to four months

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

  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

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

• Pharmacokinetics (PK) of Lapatinib

  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)

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

Other Outcomes (1)

• Tumor Response in the Non-Targeted Population Through the End of Treatment

  Baseline and then every 8 weeks through end of treatment

Study Arms (1)

lapatinib

OTHER

Randomized, 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.

Drug: GW572016 (lapatinib)

Interventions

GW572016 (lapatinib) DRUG

tyrosine kinase inhibitor

lapatinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• Subjects must complete all screening assessments as outlined in the protocol.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (31)

GSK Investigational Site

Jasper, Alabama, 35501, United States

Location

GSK Investigational Site

Greenbrae, California, 94904-2007, United States

Location

GSK Investigational Site

La Jolla, California, 92037, United States

Location

GSK Investigational Site

Long Beach, California, 90813, United States

Location

GSK Investigational Site

Poway, California, 92064, United States

Location

GSK Investigational Site

Rancho Mirage, California, 92270, United States

Location

GSK Investigational Site

Washington D.C., District of Columbia, 20007, United States

Location

GSK Investigational Site

Gainsville, Florida, 32610, United States

Location

GSK Investigational Site

Elk Grove Village, Illinois, 60007, United States

Location

GSK Investigational Site

Houma, Louisiana, 70360, United States

Location

GSK Investigational Site

Metairie, Louisiana, 70006, United States

Location

GSK Investigational Site

Lebanon, New Hampshire, 03756, United States

Location

GSK Investigational Site

New Brunswick, New Jersey, 08901, United States

Location

GSK Investigational Site

Santa Fe, New Mexico, 87505, United States

Location

GSK Investigational Site

Nyack, New York, 10960, United States

Location

GSK Investigational Site

Chapel Hill, North Carolina, 27599-7600, United States

Location

GSK Investigational Site

Durham, North Carolina, 27707, United States

Location

GSK Investigational Site

Cleveland, Ohio, 44106, United States

Location

GSK Investigational Site

Portland, Oregon, 97213, United States

Location

GSK Investigational Site

Philadelphia, Pennsylvania, 19140, United States

Location

GSK Investigational Site

Nashville, Tennessee, 37203, United States

Location

GSK Investigational Site

Corpus Christi, Texas, 78412, United States

Location

GSK Investigational Site

Houston, Texas, 77030, United States

Location

GSK Investigational Site

Calgary, Alberta, T2N 4N2, Canada

Location

GSK Investigational Site

Edmonton, Alberta, T6G 1Z2, Canada

Location

GSK Investigational Site

Kingston, Ontario, K7L 5P9, Canada

Location

GSK Investigational Site

Kitchener, Ontario, N2G 1G3, Canada

Location

GSK Investigational Site

Ottawa, Ontario, K1H 1C4, Canada

Location

GSK Investigational Site

Toronto, Ontario, M5G 2M9, Canada

Location

GSK Investigational Site

Greenfield Park, Quebec, J4V 2H1, Canada

Location

GSK Investigational Site

Lévis, Quebec, G6V 3Z1, Canada

Location

Related Publications (2)

• 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;

  BACKGROUND

• 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.

  PMID: 20215545 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Neoplasm Metastasis

Interventions

Lapatinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

Based on interim analysis and predefined stopping rules for futility, the study was discontinued due to lack of efficacy. At that time, no additional participants were added; enrolled participants could continue on treatment, following the protocol.

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 13, 2003
• First Posted: November 17, 2003
• Study Start: November 1, 2003
• Primary Completion: July 1, 2008
• Study Completion: July 1, 2008
• Last Updated: February 28, 2017
• Results First Posted: January 6, 2010

Record last verified: 2017-01

Locations

CA (8); US (23)