Clinical trial NCT00680901: LOGiC - Lapatinib Optimization Study in ErbB2 (HER2) Positive Gastric Cancer: A Phase III Global, Blinded Study Designed to Evaluate Clinical Endpoints and Safety of Chemotherapy Plus Lapatinib
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Neoplasms, Gastrointestinal Tract
Keywords: unresectable
HER2
ErbB2
TYKERB
capecitabine
CapeOx
gastric/esophageal cancer
GE junction
metastatic
lapatinib
oxaliplatin
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2008-05-20
Enrollment: 545
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Overall Survival
timeFrame: From randomization until death due to any cause (average of 51 weeks)
measure: Overall Survival in All Randomized Participants
timeFrame: From randomization until death due to any cause (average of 51 weeks)
Secondary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: From randomization until the earliest date of disease progression or death due to any cause (average of 30 weeks)
measure: Number of Participants With a Response of Confirmed Complete Response (CR) or Confirmed Partial Response (PR)
timeFrame: From randomization until the date of the first documented response of CR or PR (average of 9 weeks)
measure: Number of Participants With Clinical Benefit (CB)
timeFrame: From randomization until disease progression (PD) or death due to any cause (average of 30 weeks)
measure: Time to Response (TTR)
timeFrame: From Baseline (Day 1) until the first documented evidence of confirmed CR or PR (average of 9 weeks)
measure: Duration of Response (DOR)
timeFrame: 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)
measure: Number of Participants With Any Non-serious Adverse Event (AE: Occurring in >=5% Participants in Any Treatment Arm) or Any Serious Adverse Event (SAE)
timeFrame: From the first dose of study medication until 30 days after the last dose (average of 229 days)
measure: Number of Participants With Adverse Events of the Indicated Severity, Per the National Cancer Institute (NCI) Common Terminology Criteria in Adverse Events (CTCAE)
timeFrame: From the first dose of study medication until 30 days after the last dose (average of 229 days)
measure: 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
timeFrame: From Baseline (Day1) to Week 36
measure: Mean Change in Scores on the EORTC Quality of Life (QOL) Questionnaire of Stomach 22 (QLQ-STO22) From Baseline to Week 36
timeFrame: From Baseline (Day1) to Week 36
measure: Mean Change in Scores on the Questionnaire EuroQoL-5 Dimensions (EQ-5D) From Baseline to Week 36
timeFrame: From Baseline (Day1) to Week 36
measure: Number of Participants With a Worst-case on Therapy Grade 3 or Grade 4 for the Indicated Clinical Chemistry Parameters
timeFrame: From Baseline (Day 1) until 28 days after the last dose (average of 239 days)
measure: Number of Participants With a Worst-case on Therapy Grade 3 or Grade 4 for the Indicated Hematology Parameters
timeFrame: From Baseline (Day 1) until 28 days after the last dose (average of 239 days)
Other outcomes:
Locations:
city: Alhambra
country: United States
facility: Novartis Investigative Site
state: California
city: Fullerton
country: United States
facility: Novartis Investigative Site
state: California
city: La Verne
country: United States
facility: Novartis Investigative Site
state: California
city: Northridge
country: United States
facility: Novartis Investigative Site
state: California
city: Oxnard
country: United States
facility: Novartis Investigative Site
state: California
city: Redondo Beach
country: United States
facility: Novartis Investigative Site
state: California
city: Santa Maria
country: United States
facility: Novartis Investigative Site
state: California
city: Santa Monica
country: United States
facility: Novartis Investigative Site
state: California
city: Terre Haute
country: United States
facility: Novartis Investigative Site
state: Indiana
city: Henderson
country: United States
facility: Novartis Investigative Site
state: Nevada
city: Ciudad Aut6noma de Buenos Aires
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Quilmes
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Neuquen
country: Argentina
facility: Novartis Investigative Site
state: Neuquén
city: Cipolletti
country: Argentina
facility: Novartis Investigative Site
state: Río Negro
city: Rosario
country: Argentina
facility: Novartis Investigative Site
state: Santa Fe
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: Novartis Investigative Site
city: La Rioja
country: Argentina
facility: Novartis Investigative Site
city: Santa Fe
country: Argentina
facility: Novartis Investigative Site
city: Tucuman
country: Argentina
facility: Novartis Investigative Site
city: Belo Horizonte
country: Brazil
facility: Novartis Investigative Site
state: Minas Gerais
city: Belo Horizonte
country: Brazil
facility: Novartis Investigative Site
state: Minas Gerais
city: Porto Alegre
country: Brazil
facility: Novartis Investigative Site
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Novartis Investigative Site
state: Rio Grande Do Sul
city: Florianopolis
country: Brazil
facility: Novartis Investigative Site
state: Santa Catarina
city: Barretos
country: Brazil
facility: Novartis Investigative Site
state: São Paulo
city: Jau
country: Brazil
facility: Novartis Investigative Site
state: São Paulo
city: Santo Andre
country: Brazil
facility: Novartis Investigative Site
state: São Paulo
city: Sao Paulo
country: Brazil
facility: Novartis Investigative Site
state: São Paulo
city: Sao Paulo
country: Brazil
facility: Novartis Investigative Site
state: São Paulo
city: Sao Paulo
country: Brazil
facility: Novartis Investigative Site
state: São Paulo
city: Rio de Janeiro
country: Brazil
facility: Novartis Investigative Site
city: Edmonton
country: Canada
facility: Novartis Investigative Site
state: Alberta
city: Vancouver
country: Canada
facility: Novartis Investigative Site
state: British Columbia
city: Saint John
country: Canada
facility: Novartis Investigative Site
state: New Brunswick
city: London
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Temuco
country: Chile
facility: Novartis Investigative Site
state: Región De La Araucania
city: Santiago
country: Chile
facility: Novartis Investigative Site
state: Región Metro De Santiago
city: Vina del Mar
country: Chile
facility: Novartis Investigative Site
state: Valparaíso
city: Santiago
country: Chile
facility: Novartis Investigative Site
city: Hefei
country: China
facility: Novartis Investigative Site
state: Anhui
city: Guangzhou
country: China
facility: Novartis Investigative Site
state: Guangdong
city: Ha Er Bin
country: China
facility: Novartis Investigative Site
state: Heilongjiang
city: Nanjing
country: China
facility: Novartis Investigative Site
state: Jiangsu
city: Changchun
country: China
facility: Novartis Investigative Site
state: Jilin
city: Chengdu
country: China
facility: Novartis Investigative Site
state: Sichuan
city: Beijing
country: China
facility: Novartis Investigative Site
city: Beijing
country: China
facility: Novartis Investigative Site
city: Beijing
country: China
facility: Novartis Investigative Site
city: Fuzhou
country: China
facility: Novartis Investigative Site
city: Hangzhou
country: China
facility: Novartis Investigative Site
city: Qingdao
country: China
facility: Novartis Investigative Site
city: Shanghai
country: China
facility: Novartis Investigative Site
city: Shanghai
country: China
facility: Novartis Investigative Site
city: Tianjin
country: China
facility: Novartis Investigative Site
city: Tallinn
country: Estonia
facility: Novartis Investigative Site
city: Tartu
country: Estonia
facility: Novartis Investigative Site
city: Pokfulam
country: Hong Kong
facility: Novartis Investigative Site
city: Tuen Mun
country: Hong Kong
facility: Novartis Investigative Site
city: Gyor
country: Hungary
facility: Novartis Investigative Site
city: Kaposvar
country: Hungary
facility: Novartis Investigative Site
city: Kecskemet
country: Hungary
facility: Novartis Investigative Site
city: Miskolc
country: Hungary
facility: Novartis Investigative Site
city: Pecs
country: Hungary
facility: Novartis Investigative Site
city: Szeged
country: Hungary
facility: Novartis Investigative Site
city: Szolnok
country: Hungary
facility: Novartis Investigative Site
city: Calcutta
country: India
facility: Novartis Investigative Site
city: Coimbatore
country: India
facility: Novartis Investigative Site
city: Kochi
country: India
facility: Novartis Investigative Site
city: Kochi
country: India
facility: Novartis Investigative Site
city: Kolkata
country: India
facility: Novartis Investigative Site
city: Nagpur
country: India
facility: Novartis Investigative Site
city: New Delhi
country: India
facility: Novartis Investigative Site
city: Parel
country: India
facility: Novartis Investigative Site
city: Pune
country: India
facility: Novartis Investigative Site
city: Trivandrum
country: India
facility: Novartis Investigative Site
city: Beer-Sheva
country: Israel
facility: Novartis Investigative Site
city: Haifa
country: Israel
facility: Novartis Investigative Site
city: Jerusalem
country: Israel
facility: Novartis Investigative Site
city: Petah-Tikva
country: Israel
facility: Novartis Investigative Site
city: Ramat Gan
country: Israel
facility: Novartis Investigative Site
city: Rehovot
country: Israel
facility: Novartis Investigative Site
city: Tel Aviv
country: Israel
facility: Novartis Investigative Site
city: Zrifin
country: Israel
facility: Novartis Investigative Site
city: L'Aquila
country: Italy
facility: Novartis Investigative Site
state: Abruzzo
city: Rionero In Vulture (PZ)
country: Italy
facility: Novartis Investigative Site
state: Basilicata
city: Cesena
country: Italy
facility: Novartis Investigative Site
state: Emilia-Romagna
city: Meldola (FC)
country: Italy
facility: Novartis Investigative Site
state: Emilia-Romagna
city: Modena
country: Italy
facility: Novartis Investigative Site
state: Emilia-Romagna
city: Parma
country: Italy
facility: Novartis Investigative Site
state: Emilia-Romagna
city: Piacenza
country: Italy
facility: Novartis Investigative Site
state: Emilia-Romagna
city: Rimini
country: Italy
facility: Novartis Investigative Site
state: Emilia-Romagna
city: Udine
country: Italy
facility: Novartis Investigative Site
state: Friuli-Venezia-Giulia
city: Roma
country: Italy
facility: Novartis Investigative Site
state: Lazio
city: Roma
country: Italy
facility: Novartis Investigative Site
state: Lazio
city: Roma
country: Italy
facility: Novartis Investigative Site
state: Lazio
city: Genova
country: Italy
facility: Novartis Investigative Site
state: Liguria
city: Bergamo
country: Italy
facility: Novartis Investigative Site
state: Lombardia
city: Treviglio (BG)
country: Italy
facility: Novartis Investigative Site
state: Lombardia
city: Pesasro
country: Italy
facility: Novartis Investigative Site
state: Marche
city: Bari
country: Italy
facility: Novartis Investigative Site
state: Puglia
city: Firenze
country: Italy
facility: Novartis Investigative Site
state: Toscana
city: Macerata
country: Italy
facility: Novartis Investigative Site
city: Busan
country: Korea, Republic of
facility: Novartis Investigative Site
city: Daegu
country: Korea, Republic of
facility: Novartis Investigative Site
city: Hwasun
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seodaemun-gu, Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Suwon, Kyonggi-do
country: Korea, Republic of
facility: Novartis Investigative Site
city: Suwon
country: Korea, Republic of
facility: Novartis Investigative Site
city: Acapulco
country: Mexico
facility: Novartis Investigative Site
state: Guerrero
city: Mexico City
country: Mexico
facility: Novartis Investigative Site
city: Oaxaca
country: Mexico
facility: Novartis Investigative Site
city: Amsterdam
country: Netherlands
facility: Novartis Investigative Site
city: Leeuwarden
country: Netherlands
facility: Novartis Investigative Site
city: Nijmegen
country: Netherlands
facility: Novartis Investigative Site
city: Callao
country: Peru
facility: Novartis Investigative Site
city: Lima
country: Peru
facility: Novartis Investigative Site
city: Lima
country: Peru
facility: Novartis Investigative Site
city: Gdansk
country: Poland
facility: Novartis Investigative Site
city: Krakow
country: Poland
facility: Novartis Investigative Site
city: Olsztyn
country: Poland
facility: Novartis Investigative Site
city: Olsztyn
country: Poland
facility: Novartis Investigative Site
city: Plock
country: Poland
facility: Novartis Investigative Site
city: Poznan
country: Poland
facility: Novartis Investigative Site
city: Rybnik
country: Poland
facility: Novartis Investigative Site
city: Slupsk
country: Poland
facility: Novartis Investigative Site
city: Szczecin
country: Poland
facility: Novartis Investigative Site
city: Torun
country: Poland
facility: Novartis Investigative Site
city: Warszawa
country: Poland
facility: Novartis Investigative Site
city: Warszawa
country: Poland
facility: Novartis Investigative Site
city: San Juan
country: Puerto Rico
facility: Novartis Investigative Site
city: Chelyabinsk
country: Russian Federation
facility: Novartis Investigative Site
city: Kirov
country: Russian Federation
facility: Novartis Investigative Site
city: Kursk
country: Russian Federation
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: Omsk
country: Russian Federation
facility: Novartis Investigative Site
city: Ryazan
country: Russian Federation
facility: Novartis Investigative Site
city: Saratov
country: Russian Federation
facility: Novartis Investigative Site
city: Sochi
country: Russian Federation
facility: Novartis Investigative Site
city: St. Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: St. Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: Stavropol
country: Russian Federation
facility: Novartis Investigative Site
city: Ufa,
country: Russian Federation
facility: Novartis Investigative Site
city: Tainan
country: Taiwan
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Taoyuan County
country: Taiwan
facility: Novartis Investigative Site
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Hatyai, Songkhla
country: Thailand
facility: Novartis Investigative Site
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Gaziantep
country: Turkey
facility: Novartis Investigative Site
city: Trabzon
country: Turkey
facility: Novartis Investigative Site
city: Cherkasy
country: Ukraine
facility: Novartis Investigative Site
city: Chernivtsi
country: Ukraine
facility: Novartis Investigative Site
city: Dnepropetrovsk
country: Ukraine
facility: Novartis Investigative Site
city: Dnipropetrovsk
country: Ukraine
facility: Novartis Investigative Site
city: Donetsk
country: Ukraine
facility: Novartis Investigative Site
city: Ivano-Frankivsk
country: Ukraine
facility: Novartis Investigative Site
city: Kharkiv
country: Ukraine
facility: Novartis Investigative Site
city: Kryvyi Rih
country: Ukraine
facility: Novartis Investigative Site
city: Kyiv
country: Ukraine
facility: Novartis Investigative Site
city: Kyiv
country: Ukraine
facility: Novartis Investigative Site
city: Kyiv
country: Ukraine
facility: Novartis Investigative Site
city: Lutsk,
country: Ukraine
facility: Novartis Investigative Site
city: Lviv
country: Ukraine
facility: Novartis Investigative Site
city: Odessa
country: Ukraine
facility: Novartis Investigative Site
city: Plyuty
country: Ukraine
facility: Novartis Investigative Site
city: Simferopil
country: Ukraine
facility: Novartis Investigative Site
city: Simferopol
country: Ukraine
facility: Novartis Investigative Site
city: Sumy
country: Ukraine
facility: Novartis Investigative Site
city: Ternopil
country: Ukraine
facility: Novartis Investigative Site
city: Uzhgorod
country: Ukraine
facility: Novartis Investigative Site
city: Vinnitsia
country: Ukraine
facility: Novartis Investigative Site
city: Zaporizhzhia
country: Ukraine
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Chu MP, Hecht JR, Slamon D, Wainberg ZA, Bang YJ, Hoff PM, Sobrero A, Qin S, Afenjar K, Houe V, King K, Koski S, Mulder K, Hiller JP, Scarfe A, Spratlin J, Huang YJ, Khan-Wasti S, Chua N, Sawyer MB. Association of Proton Pump Inhibitors and Capecitabine Efficacy in Advanced Gastroesophageal Cancer: Secondary Analysis of the TRIO-013/LOGiC Randomized Clinical Trial. JAMA Oncol. 2017 Jun 1;3(6):767-773. doi: 10.1001/jamaoncol.2016.3358.
citation: Hecht JR, Bang YJ, Qin SK, Chung HC, Xu JM, Park JO, Jeziorski K, Shparyk Y, Hoff PM, Sobrero A, Salman P, Li J, Protsenko SA, Wainberg ZA, Buyse M, Afenjar K, Houe V, Garcia A, Kaneko T, Huang Y, Khan-Wasti S, Santillana S, Press MF, Slamon D. Lapatinib in Combination With Capecitabine Plus Oxaliplatin in Human Epidermal Growth Factor Receptor 2-Positive Advanced or Metastatic Gastric, Esophageal, or Gastroesophageal Adenocarcinoma: TRIO-013/LOGiC--A Randomized Phase III Trial. J Clin Oncol. 2016 Feb 10;34(5):443-51. doi: 10.1200/JCO.2015.62.6598. Epub 2015 Nov 30.