Overview

This trial is active, not recruiting.

Condition neoplasms, gastrointestinal tract
Treatments lapatinib, placebo, capecitabine, oxaliplatin
Phase phase 3
Targets HER2, AKT, CDK, EGFR, ERK
Sponsor GlaxoSmithKline
Start date June 2008
End date September 2012
Trial size 545 participants
Trial identifier NCT00680901, EGF110656

Summary

This is an international multi-center trial that will enroll patients with locally advanced, unresectable, or metastatic gastric, esophageal, or gastro-esophageal junction cancer whose tumors have amplification of the ErbB2 (HER2) gene. The trial will investigate whether lapatinib, when added to the chemotherapy regimen, capecitabine plus oxaliplatin (CapeOx), extends the time to progression and overall survival. Tumor ErbB2 (HER2) status must be known before trial entry. CapeOx is administered to all patients, and patients will be randomly assigned to receive either lapatinib or placebo.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Experimental)
CapeOx plus Lapatinib
lapatinib Tykerb
5 pills at 250mg each once daily
capecitabine
1700mg/m2/day in two daily doses
oxaliplatin
130mg/m2 on day 1
(Placebo Comparator)
CapeOx plus Placebo
placebo
5 pills once daily
capecitabine
1700mg/m2/day in two daily doses
oxaliplatin
130mg/m2 on day 1

Primary Outcomes

Measure
Overall Survival
time frame: From randomization until death due to any cause (average of 51 weeks)
Overall Survival in All Randomized Participants
time frame: From randomization until death due to any cause (average of 51 weeks)

Secondary Outcomes

Measure
Progression Free Survival (PFS)
time frame: From randomization until the earliest date of disease progression or death due to any cause (average of 30 weeks)
Number of Participants With a Response of Confirmed Complete Response (CR) or Confirmed Partial Response (PR)
time frame: From randomization until the date of the first documented response of CR or PR (average of 9 weeks)
Number of Participants With Clinical Benefit (CB)
time frame: From randomization until disease progression (PD) or death due to any cause (average of 30 weeks)
Time to Response (TTR)
time frame: From Baseline (Day 1) until the first documented evidence of confirmed CR or PR (average of 9 weeks)
Duration of Response (DOR)
time frame: From the time of the first documented evidence of a confirmed CR or PR until the earliest date of disease progression or death due to any cause (average of 36 weeks)
Number of Participants With Any Non-serious Adverse Event (AE: Occurring in >=5% Participants in Any Treatment Arm) or Any Serious Adverse Event (SAE)
time frame: From the first dose of study medication until 30 days after the last dose (average of 229 days)
Number of Participants With Adverse Events of the Indicated Severity, Per the National Cancer Institute (NCI) Common Terminology Criteria in Adverse Events (CTCAE)
time frame: From the first dose of study medication until 30 days after the last dose (average of 229 days)
Mean Change in Scores on the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QOL) Questionnaire Core 30 (QLQ-C30) From Baseline to Week 36
time frame: From Baseline (Day1) to Week 36
Mean Change in Scores on the EORTC Quality of Life (QOL) Questionnaire of Stomach 22 (QLQ-STO22) From Baseline to Week 36
time frame: From Baseline (Day1) to Week 36
Mean Change in Scores on the Questionnaire EuroQoL-5 Dimensions (EQ-5D) From Baseline to Week 36
time frame: From Baseline (Day1) to Week 36
Number of Participants With a Worst-case on Therapy Grade 3 or Grade 4 for the Indicated Clinical Chemistry Parameters
time frame: From Baseline (Day 1) until 28 days after the last dose (average of 239 days)
Number of Participants With a Worst-case on Therapy Grade 3 or Grade 4 for the Indicated Hematology Parameters
time frame: From Baseline (Day 1) until 28 days after the last dose (average of 239 days)

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: Signed informed consent; Histologically confirmed gastric, esophageal, or gastro-esophageal junction adenocarcinoma; disease that is locally advanced (unresectable), metastatic, or locally recurrent disease; Measurable or non-measurable, but radiologically evaluable disease, according to RECIST; ErbB2 (HER2)positive; Age =18 years; ECOG Performance status = 2; Adequate organ function, including adequate hematologic, renal and liver function; Cardiac ejection fraction within institutional range of normal as measured by echocardiogram; Able to swallow and retain oral medications, and/or receive enteral medications via gastrectomy feeding tube; Women and men with potential to have children must be willing to practice acceptable methods of birth control during the study; Prior gastric surgery is permitted if > 3 weeks prior and recovered; Prior chemotherapy for non-gastric malignancy if > than 5 years; Prior neoadjuvant and/or adjuvant chemotherapy for early stage gastric cancer if > 6 months since completion; At least 4 weeks since prior radiotherapy; Prior biologic, hormonal, or immunologic cancer treatment if > 5 years since treatment. Exclusion Criteria: Pregnant or lactating females; Known history of active CNS disease; Uncontrolled ascites; Concurrent anti-cancer therapy; Gastric carcinoid, epidermoid, sarcomas, or squamous cell carcinoma; Prior palliative chemotherapy for the treatment of gastric cancer; Prior treatment with oxaliplatin < 12 months; Malabsorption syndrome or uncontrolled inflammatory gastrointestinal disease; Known history of uncontrolled or symptomatic angina, arrhythmias, or congestive heart failure; Pre-existing grade = 2 motor or sensory neuropathy; Uncontrolled infection; Concurrent disease or condition that would make the subject inappropriate for study participation or any serious medical condition that would interfere with the subject''s safety; Active hepatic or biliary disease; History of other malignancy except if disease-free for 5 years, a history of completely resected non-melanoma skin cancer, or a successfully treated in situ carcinoma; Unresolved or unstable serious toxicity from prior administration of another investigational drug and/or prior cancer treatment; Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent; Known history of DPD deficiency; Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to lapatinib, capecitabine, fluorouracil, platins or their excipients; Use of any investigational drug within 30 days prior randomization; Use of concurrent prohibited medications that would interact with study medications

Additional Information

Official title A Phase III Study for ErbB2 Positive Advanced or Metastatic Gastric, Esophageal, or Gastroesophageal Junction Adenocarcinoma Treated With Capecitabine Plus Oxaliplatin With or Without Lapatinib
Trial information was received from ClinicalTrials.gov and was last updated in April 2015.
Information provided to ClinicalTrials.gov by GlaxoSmithKline.
Location data was received from the National Cancer Institute and was last updated in July 2016.