Lapatinib in Combination With Weekly Paclitaxel in Patients With ErbB2 Amplified Advanced Gastric Cancer

NCT00486954 | Completed Phase 3 Results

• 1 other identifier: 104578
• Study Type: interventional
• Target: 273
• Locations: 4 countries
• Sites: 17

Brief Summary

EGF104578 is two-part study (Pilot part/Randomized part).Pilot part is designed to find the optimal (best) doses of lapatinib and paclitaxel when given together,Randomized part is designed to evaluate the overall survival in patients receiving lapatinib and paclitaxel compared to patients receiving only paclitaxel.

Conditions

Neoplasms, Gastrointestinal Tract

Keywords

lapatinib; paclitaxel; ErbB2; Gastric cancer; Advanced gastric cancer

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Dose Limiting Toxicities (DLTs) in the Pilot Part of the Study

  DLTs consisted of only drug-related toxicities (neurologic and non-neurologic DLTs). A neurologic DLT was defined as grade 3/4 clinically significant peripheral motor and/or sensitive neuropathy. Non-neurologic DLTs mainly included the following: grade 3/4 clinically significant non-hematological toxicity (except nausea), grade 4 neutropenia lasting \>=7 days, thrombocytopenia (\<=25000 cells per cubic millimeter), inability to begin next treatment within 2 weeks of scheduled dosing due to unresolved toxicity, treatment delay (due to toxicity) of \>5 days, for Days 8 or 15 of weekly paclitaxel.

  28 days

• Overall Survival (OS) in the Randomized Part of the Study

  OS was defined as the time from randomization until death due to any cause. For participants who did not die, time to death was censored at the time of last contact. For censored participants, time to death was defined as the time from randomization to the time of last contact.

  From randomization until death due to any cause (up to 42.58 months)

Secondary Outcomes (43)

• Maximum Plasma Concentration (Cmax) of Lapatinib in the Pilot Part of the Study

  Days 8 and 14

• Time to Cmax (Tmax) of Lapatinib in the Pilot Part of the Study

  Days 8 and 14

• Area Under the Concentration-time Curve From Time Zero to 24 Hours (AUC[0-24]) of Lapatinib in the Pilot Part of the Study

  Days 8 and 14

• Cmax of Paclitaxel in the Pilot Part of the Study

  Days 1 and 8

• Tmax of Paclitaxel in the Pilot Part of the Study

  Days 1 and 8

Study Arms (2)

Paclitaxel plus Lapatinib

EXPERIMENTAL

6 pills of lapatinib at 250 mg each once daily and infusion of paclitaxel at 80 mglm2 weekly

Drug: Lapatinib; Drug: Paclitaxel

Paclitaxel alone

ACTIVE COMPARATOR

Infusion of paclitaxel at 80 mglm2 weekly

Drug: Paclitaxel

Interventions

Lapatinib DRUG

6 pills at 250 mg each once daily

Also known as: Lapatinib: Tykerb, Tyverb

Paclitaxel plus Lapatinib

Paclitaxel DRUG

Infusion at 80 mg/m2 weekly

Paclitaxel alone; Paclitaxel plus Lapatinib

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Specific Information regarding warnings, precautions, contraindications, adverse events, and other pertinent information on the investigational product that may impact subject eligibility is provided in the Investigator's Brochure (IB) Pilot Part
• Subjects eligible for enrollment in the Pilot Part of the study must meet all of the following criteria:
• Signed informed consent
• Male or female; ≥ 20 years (at the time of giving consent)
• Any histologically or cytologically confirmed gastric carcinoma independent of tumor ErbB2 status
• Subjects who have received one prior regimen for gastric carcinoma and developed disease progression or recurrence. The regimen must have contained 5-fluoropyrimidine and/or cisplatin
• Left ventricular ejection fraction (LVEF) within institutional range of normal as measured by echocardiogram (ECHO). Multigated acquisition (MUGA) scans will be accepted in cases where an echocardiogram cannot be performed or is inconclusive (LVEF of ≥50% required if normal range of LVEF is not provided by institution)
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1
• Able to swallow and retain oral medication
• Women and men with potential to have children must be willing to practice acceptable methods of birth control during the study
• Washout period from the prior last therapy as follows; Chemotherapy (except for agents below) 4 weeks (I.V) Chemotherapy (except for agents below) 2 weeks (P.O) Trastuzumab, Bevacizumab 4 weeks Mitomycin-C, nitrosourea 6 weeks Radiotherapy, Immunotherapy, Biologic therapy and Surgery (except for minor surgical procedure) 2 weeks
• Willing to complete all screening assessments as outlined in the protocol
• Adequate organ function as defined in Table 2 Baseline Laboratory Values
• Able to be hospitalized for PK analysis during cycle 1
• Life expectancy of at least 12 weeks from the first dose of study treatment)

You may not qualify if:

• Subjects meeting any of the following criteria must not be enrolled in the study:
• Pregnant or lactating female at anytime during the study
• Planned concurrent anti-cancer therapy (chemotherapy, radiotherapy, immunotherapy, biologic therapy, hormonal therapy) while taking investigational treatment
• Unresolved or unstable, serious toxicity from prior cancer treatment (any toxicities greater than grade 2)
• Peripheral neuropathy of Grade 2 or greater
• Malabsorption syndrome, disease significantly affecting gastrointestinal function. Subjects with ulcerative colitis and Crohn's disease are also excluded
• History of other malignancy. However, 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
• Life threatening infection
• Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent
• Known history of uncontrolled or symptomatic angina, arrhythmias, or congestive heart failure
• Known history or clinical evidence of central nervous system (CNS) metastasis
• Concurrent treatment with prohibited medications, including herbal remedies and Chinese traditional medicines
• Concurrent treatment with an investigational agent within 28 days prior to the administration of paclitaxel and/or lapatinib
• Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to paclitaxel, including polyethoxylated castor oil, alcohol, or lapatinib or their excipients

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (17)

GSK Investigational Site

Guangzhou, Guangdong, 510060, China

Location

GSK Investigational Site

Beijing, 100021, China

Location

GSK Investigational Site

Beijing, 100071, China

Location

GSK Investigational Site

Shanghai, 200032, China

Location

GSK Investigational Site

Tokyo, 113-8677, Japan

Location

GSK Investigational Site

Hwasun, 519-809, South Korea

Location

GSK Investigational Site

Seongnam-si Gyeonggi-do, 463-707, South Korea

Location

GSK Investigational Site

Seoul, 110-744, South Korea

Location

GSK Investigational Site

Seoul, 120-752, South Korea

Location

GSK Investigational Site

Seoul, 135-710, South Korea

Location

GSK Investigational Site

Kaohsiung City, 807, Taiwan

Location

GSK Investigational Site

Niaosong Township, Kaohsiung, 833, Taiwan

Location

GSK Investigational Site

Tainan, 704, Taiwan

Location

GSK Investigational Site

Tainan County, 736, Taiwan

Location

GSK Investigational Site

Taipei, 100, Taiwan

Location

GSK Investigational Site

Taipei, 112, Taiwan

Location

GSK Investigational Site

Tau-Yuan County, 333, Taiwan

Location

MeSH Terms

Conditions

Neoplasms; Stomach Neoplasms

Interventions

Lapatinib; Paclitaxel

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

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 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 13, 2007
• First Posted: June 15, 2007
• Study Start: July 1, 2007
• Primary Completion: January 1, 2012
• Study Completion: October 1, 2012
• Last Updated: June 20, 2013
• Results First Posted: February 7, 2013

Record last verified: 2013-01

Locations

KR (5); JP (1); TW (7); CN (4)