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

Neoplasms, Gastrointestinal Tract Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00680901
• Other study ID #: EGF110656
• Secondary ID: 2007-005725-29CL
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: June 4, 2008
• Est. completion date: January 22, 2025

Study information

• Verified date: May 2024
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 545
• Est. completion date: January 22, 2025
• Est. primary completion date: September 24, 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Digestive System Neoplasms
• Gastrointestinal Neoplasms
• Neoplasms, Gastrointestinal Tract

Intervention

Drug:
• Lapatinib
5 pills at 250mg each once daily
• Placebo
5 pills once daily
• Capecitabine
1700mg/m2/day in two daily doses
• Oxaliplatin
130mg/m2 on day 1

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Cipolletti	Río Negro
Argentina	Novartis Investigative Site	Ciudad Aut6noma de Buenos Aires	Buenos Aires
Argentina	Novartis Investigative Site	Ciudad Autonoma de Buenos Aires
Argentina	Novartis Investigative Site	La Rioja
Argentina	Novartis Investigative Site	Neuquen	Neuquén
Argentina	Novartis Investigative Site	Quilmes	Buenos Aires
Argentina	Novartis Investigative Site	Rosario	Santa Fe
Argentina	Novartis Investigative Site	Santa Fe
Argentina	Novartis Investigative Site	Tucuman
Brazil	Novartis Investigative Site	Barretos	São Paulo
Brazil	Novartis Investigative Site	Belo Horizonte	Minas Gerais
Brazil	Novartis Investigative Site	Belo Horizonte	Minas Gerais
Brazil	Novartis Investigative Site	Florianopolis	Santa Catarina
Brazil	Novartis Investigative Site	Jau	São Paulo
Brazil	Novartis Investigative Site	Porto Alegre	Rio Grande Do Sul
Brazil	Novartis Investigative Site	Porto Alegre	Rio Grande Do Sul
Brazil	Novartis Investigative Site	Rio de Janeiro
Brazil	Novartis Investigative Site	Santo Andre	São Paulo
Brazil	Novartis Investigative Site	Sao Paulo	São Paulo
Brazil	Novartis Investigative Site	Sao Paulo	São Paulo
Brazil	Novartis Investigative Site	Sao Paulo	São Paulo
Canada	Novartis Investigative Site	Edmonton	Alberta
Canada	Novartis Investigative Site	London	Ontario
Canada	Novartis Investigative Site	Montreal	Quebec
Canada	Novartis Investigative Site	Montreal	Quebec
Canada	Novartis Investigative Site	Saint John	New Brunswick
Canada	Novartis Investigative Site	Toronto	Ontario
Canada	Novartis Investigative Site	Toronto	Ontario
Canada	Novartis Investigative Site	Toronto	Ontario
Canada	Novartis Investigative Site	Vancouver	British Columbia
Chile	Novartis Investigative Site	Santiago	Región Metro De Santiago
Chile	Novartis Investigative Site	Santiago
Chile	Novartis Investigative Site	Temuco	Región De La Araucania
Chile	Novartis Investigative Site	Vina del Mar	Valparaíso
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Changchun	Jilin
China	Novartis Investigative Site	Chengdu	Sichuan
China	Novartis Investigative Site	Fuzhou
China	Novartis Investigative Site	Guangzhou	Guangdong
China	Novartis Investigative Site	Ha Er Bin	Heilongjiang
China	Novartis Investigative Site	Hangzhou
China	Novartis Investigative Site	Hefei	Anhui
China	Novartis Investigative Site	Nanjing	Jiangsu
China	Novartis Investigative Site	Qingdao
China	Novartis Investigative Site	Shanghai
China	Novartis Investigative Site	Shanghai
China	Novartis Investigative Site	Tianjin
Estonia	Novartis Investigative Site	Tallinn
Estonia	Novartis Investigative Site	Tartu
Hong Kong	Novartis Investigative Site	Pokfulam
Hong Kong	Novartis Investigative Site	Tuen Mun
Hungary	Novartis Investigative Site	Gyor
Hungary	Novartis Investigative Site	Kaposvar
Hungary	Novartis Investigative Site	Kecskemet
Hungary	Novartis Investigative Site	Miskolc
Hungary	Novartis Investigative Site	Pecs
Hungary	Novartis Investigative Site	Szeged
Hungary	Novartis Investigative Site	Szolnok
India	Novartis Investigative Site	Calcutta
India	Novartis Investigative Site	Coimbatore
India	Novartis Investigative Site	Kochi
India	Novartis Investigative Site	Kochi
India	Novartis Investigative Site	Kolkata
India	Novartis Investigative Site	Nagpur
India	Novartis Investigative Site	New Delhi
India	Novartis Investigative Site	Parel
India	Novartis Investigative Site	Pune
India	Novartis Investigative Site	Trivandrum
Israel	Novartis Investigative Site	Beer-Sheva
Israel	Novartis Investigative Site	Haifa
Israel	Novartis Investigative Site	Jerusalem
Israel	Novartis Investigative Site	Petah-Tikva
Israel	Novartis Investigative Site	Ramat Gan
Israel	Novartis Investigative Site	Rehovot
Israel	Novartis Investigative Site	Tel Aviv
Israel	Novartis Investigative Site	Zrifin
Italy	Novartis Investigative Site	Bari	Puglia
Italy	Novartis Investigative Site	Bergamo	Lombardia
Italy	Novartis Investigative Site	Cesena	Emilia-Romagna
Italy	Novartis Investigative Site	Firenze	Toscana
Italy	Novartis Investigative Site	Genova	Liguria
Italy	Novartis Investigative Site	L'Aquila	Abruzzo
Italy	Novartis Investigative Site	Macerata
Italy	Novartis Investigative Site	Meldola (FC)	Emilia-Romagna
Italy	Novartis Investigative Site	Modena	Emilia-Romagna
Italy	Novartis Investigative Site	Parma	Emilia-Romagna
Italy	Novartis Investigative Site	Pesasro	Marche
Italy	Novartis Investigative Site	Piacenza	Emilia-Romagna
Italy	Novartis Investigative Site	Rimini	Emilia-Romagna
Italy	Novartis Investigative Site	Rionero In Vulture (PZ)	Basilicata
Italy	Novartis Investigative Site	Roma	Lazio
Italy	Novartis Investigative Site	Roma	Lazio
Italy	Novartis Investigative Site	Roma	Lazio
Italy	Novartis Investigative Site	Treviglio (BG)	Lombardia
Italy	Novartis Investigative Site	Udine	Friuli-Venezia-Giulia
Korea, Republic of	Novartis Investigative Site	Busan
Korea, Republic of	Novartis Investigative Site	Daegu
Korea, Republic of	Novartis Investigative Site	Hwasun
Korea, Republic of	Novartis Investigative Site	Seodaemun-gu, Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Suwon
Korea, Republic of	Novartis Investigative Site	Suwon, Kyonggi-do
Mexico	Novartis Investigative Site	Acapulco	Guerrero
Mexico	Novartis Investigative Site	Mexico City
Mexico	Novartis Investigative Site	Oaxaca
Netherlands	Novartis Investigative Site	Amsterdam
Netherlands	Novartis Investigative Site	Leeuwarden
Netherlands	Novartis Investigative Site	Nijmegen
Peru	Novartis Investigative Site	Callao
Peru	Novartis Investigative Site	Lima
Peru	Novartis Investigative Site	Lima
Poland	Novartis Investigative Site	Gdansk
Poland	Novartis Investigative Site	Krakow
Poland	Novartis Investigative Site	Olsztyn
Poland	Novartis Investigative Site	Olsztyn
Poland	Novartis Investigative Site	Plock
Poland	Novartis Investigative Site	Poznan
Poland	Novartis Investigative Site	Rybnik
Poland	Novartis Investigative Site	Slupsk
Poland	Novartis Investigative Site	Szczecin
Poland	Novartis Investigative Site	Torun
Poland	Novartis Investigative Site	Warszawa
Poland	Novartis Investigative Site	Warszawa
Puerto Rico	Novartis Investigative Site	San Juan
Russian Federation	Novartis Investigative Site	Chelyabinsk
Russian Federation	Novartis Investigative Site	Kirov
Russian Federation	Novartis Investigative Site	Kursk
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Omsk
Russian Federation	Novartis Investigative Site	Ryazan
Russian Federation	Novartis Investigative Site	Saratov
Russian Federation	Novartis Investigative Site	Sochi
Russian Federation	Novartis Investigative Site	St. Petersburg
Russian Federation	Novartis Investigative Site	St. Petersburg
Russian Federation	Novartis Investigative Site	Stavropol
Russian Federation	Novartis Investigative Site	Ufa,
Taiwan	Novartis Investigative Site	Tainan
Taiwan	Novartis Investigative Site	Taipei
Taiwan	Novartis Investigative Site	Taipei
Taiwan	Novartis Investigative Site	Taoyuan County
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Hatyai, Songkhla
Turkey	Novartis Investigative Site	Ankara
Turkey	Novartis Investigative Site	Gaziantep
Turkey	Novartis Investigative Site	Trabzon
Ukraine	Novartis Investigative Site	Cherkasy
Ukraine	Novartis Investigative Site	Chernivtsi
Ukraine	Novartis Investigative Site	Dnepropetrovsk
Ukraine	Novartis Investigative Site	Dnipropetrovsk
Ukraine	Novartis Investigative Site	Donetsk
Ukraine	Novartis Investigative Site	Ivano-Frankivsk
Ukraine	Novartis Investigative Site	Kharkiv
Ukraine	Novartis Investigative Site	Kryvyi Rih
Ukraine	Novartis Investigative Site	Kyiv
Ukraine	Novartis Investigative Site	Kyiv
Ukraine	Novartis Investigative Site	Kyiv
Ukraine	Novartis Investigative Site	Lutsk,
Ukraine	Novartis Investigative Site	Lviv
Ukraine	Novartis Investigative Site	Odessa
Ukraine	Novartis Investigative Site	Plyuty
Ukraine	Novartis Investigative Site	Simferopil
Ukraine	Novartis Investigative Site	Simferopol
Ukraine	Novartis Investigative Site	Sumy
Ukraine	Novartis Investigative Site	Ternopil
Ukraine	Novartis Investigative Site	Uzhgorod
Ukraine	Novartis Investigative Site	Vinnitsia
Ukraine	Novartis Investigative Site	Zaporizhzhia
United States	Novartis Investigative Site	Alhambra	California
United States	Novartis Investigative Site	Fullerton	California
United States	Novartis Investigative Site	Henderson	Nevada
United States	Novartis Investigative Site	La Verne	California
United States	Novartis Investigative Site	Northridge	California
United States	Novartis Investigative Site	Oxnard	California
United States	Novartis Investigative Site	Redondo Beach	California
United States	Novartis Investigative Site	Santa Maria	California
United States	Novartis Investigative Site	Santa Monica	California
United States	Novartis Investigative Site	Terre Haute	Indiana

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Canada,  Chile,  China,  Estonia,  Hong Kong,  Hungary,  India,  Israel,  Italy,  Korea, Republic of,  Mexico,  Netherlands,  Peru,  Poland,  Puerto Rico,  Russian Federation,  Taiwan,  Thailand,  Turkey,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival	Overall Survival is defined as the time from randomization until death due to any cause. Participants who had not died were censored at the follow-up visit as either follow-up ended or follow-up ongoing.	From randomization until death due to any cause (average of 51 weeks)
Primary	Overall Survival in All Randomized Participants	Overall Survival is defined as the time from randomization until death due to any cause. Participants who had not died were censored at the follow-up visit as either follow-up ended or follow-up ongoing.	From randomization until death due to any cause (average of 51 weeks)
Secondary	Progression Free Survival (PFS)	PFS is defined as the interval between the date of randomization and the earliest date of disease progression (PD) or death due to any cause. Per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0, PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started or the appearance of >= 1 new lesion. Participants who did not have a radiological assessed PD but had symptomatic PD were also counted. Participants who had neither progressed nor died were censored at the follow-up visit as either follow-up ended or follow-up ongoing. Participants who received non-study anti-cancer therapies before disease progression were treated as censored.	From randomization until the earliest date of disease progression or death due to any cause (average of 30 weeks)
Secondary	Number of Participants With a Response of Confirmed Complete Response (CR) or Confirmed Partial Response (PR)	A participant was defined as a responder if he/she achieved either a CR (the disappearance of all target and non-target lesions) or a PR (at least a 30% decrease in the sum of the longest diameters [LD] of target lesions, taking as a reference the Baseline sum LD) as assessed by the investigator (confirmed by radiographic imaging within 4 weeks from initial observations).	From randomization until the date of the first documented response of CR or PR (average of 9 weeks)
Secondary	Number of Participants With Clinical Benefit (CB)	CB is defined as evidence of a CR (disappearance of all target and non-target lesions) or PR (at least a 30% decrease in the sum of the LD of target lesions, taking as a reference the Baseline sum LD) at any time or stable disease (SD, neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started) as assessed by the investigator.	From randomization until disease progression (PD) or death due to any cause (average of 30 weeks)
Secondary	Time to Response (TTR)	TTR is defined as the time from randomization until the date of the first documented evidence of CR (the disappearance if all target and non-target lesions) or PR (at least a 30% decrease in the sum of the LD of target lesions, taking a reference the Baseline sum LD) as assessed by the investigator.	From Baseline (Day 1) until the first documented evidence of confirmed CR or PR (average of 9 weeks)
Secondary	Duration of Response (DOR)	DOR is defined as the time from the first documented evidence of a CR (the disappearance of all target and non-target lesions) or PR (at least a 30% decrease in the sum of the LD of target lesions, taking as a reference the Baseline sum LD) until the first documented sign of PD or death due to any cause. Per RECIST, PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started or the appearance of >=1 new lesion. Participants who had neither progressed nor died were censored at the follow-up visit as either follow-up ended or follow-up ongoing. Participants who received non-study anti-cancer therapies before disease progression were treated as censored.	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)
Secondary	Number of Participants With Any Non-serious Adverse Event (AE: Occurring in >=5% Participants in Any Treatment Arm) or Any Serious Adverse Event (SAE)	An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or is an event of possible drug-induced liver injury. Refer to the general Adverse AE/SAE module for a complete list of AEs and SAEs.	From the first dose of study medication until 30 days after the last dose (average of 229 days)
Secondary	Number of Participants With Adverse Events of the Indicated Severity, Per the National Cancer Institute (NCI) Common Terminology Criteria in Adverse Events (CTCAE)	An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or is an event of possible drug-induced liver injury. AE/SAE severity was graded according to NCI CTCAE, version 3.0: Grade (G) 1, mild; G2, moderate; G3, severe; G4, life threatening; G5, death related to toxicity.	From the first dose of study medication until 30 days after the last dose (average of 229 days)
Secondary	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	The QLQ-C30, a self administered tool used to assess HROL, consists of 30 items that assesses 15 domains consisting of 5 functional scales (s.) (physical, role, emotional, cognitive, social) and nine symptom s. or single items (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, financial difficulties) and a global health status or QOL s.. For the functional s. and symptom s. or single items, participants assessed using a 4-point s. (1=not at all; 2=a little; 3=quite a bit; 4=very much), whereas global health status or QOL was assessed using a 7-item Likert s., ranging from "poor" to "excellent." All s. and single-item scores ranged from 0 to 100. For the functional scores, a higher score indicated a better HRQOL, i.e. 0=worst HRQOL, 100=best HRQOL; for the symptom s. or single items , a higher score indicated a high level of symptoms and problems, i.e. 0=no symptoms, 100=most severe symptoms.	From Baseline (Day1) to Week 36
Secondary	Mean Change in Scores on the EORTC Quality of Life (QOL) Questionnaire of Stomach 22 (QLQ-STO22) From Baseline to Week 36	The EORTC QLQ-STO22, the Gastric module of QLQ-C30, is a self administered tool use to assess HROOL of patients with gastric cancer. It consists of 22 items consisting of nine symptom scales or single items (dysphagia, pain, reflux, eating restrictions, anxiety, dry mouth, taste, body image, hair loss) that were developed for participants with gastric cancer. For the symptom scales or single items, participants assessed using a 4-point scale (1=not at all; 2=a little; 3=quite a bit; 4=very much). All scales and single-item scores ranged from 0 to 100. For the symptom scales or single items, a higher score indicated a high level of symptoms and problems, i.e. 0=no symptoms, 100=most severe symptoms.	From Baseline (Day1) to Week 36
Secondary	Mean Change in Scores on the Questionnaire EuroQoL-5 Dimensions (EQ-5D) From Baseline to Week 36	The EQ-5D is a generic preference-based HROOL self administered tool comprising of a 5-dimensional health status measure (5D utility measure) and a visual analog rating scale feeling thermometer (T.). 5D utility measures mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. T. assesses participant's current health state. Each 5D utility question was responded to on a 3-point scale, indicating the level of impairment (1=no problem; 2=some or moderate problem(s); 3=unable, or extreme problems). The index utility values corresponding to the 243 health states were defined by the EuroQol classification and calculated based on country-specific regression coefficients. In the UK-based value set, the possible EQ-5D index utility values range from -0.594 to 1. The T. value ranges from 0 to 100. EQ-5D utility index score 0=death, 1=perfect health, -0.594 = worse than death. The T. score: 100=best imaginable health state, 0=worse imaginable health state.	From Baseline (Day1) to Week 36
Secondary	Number of Participants With a Worst-case on Therapy Grade 3 or Grade 4 for the Indicated Clinical Chemistry Parameters	Data are summarized by NCI CTCAE, version 3.0 toxicity grades. Data are reported as the number of participants who had a Grade 3 (G3) or Grade 4 (G4) toxicity for the indicated clinical chemistry parameters: G3 indicates a severe toxicity, and G4 indicates a life-threatening toxicity. Clinical chemistry parameters included: Albumin, Alkaline Phosphatase (AP), Alanine Amino Transferase (ALT), Aspartate Amino Transeferase (AST), Total Bilirubin (TB), Calcium (Hypercalcemia and Hypocalcemia), Creatine Kinase (CK), Creatinine, Glucose (Hyperglycemia [high] and Hypoglycemia [low]), Potassium (Hyperkalemia [high] and Hypokalemia [low]), Magnesium (Hypermagnesemia [high] and Hypomagnesemia [low]), and Sodium (Hypernatremia [high] and Hyponatremia [low]).	From Baseline (Day 1) until 28 days after the last dose (average of 239 days)
Secondary	Number of Participants With a Worst-case on Therapy Grade 3 or Grade 4 for the Indicated Hematology Parameters	Data are summarized by NCI CTCAE, version 3.0 toxicity grades. Data are reported as the number of participants who had a Grade 3 (G3) or Grade 4 (G4) toxicity for indicated hematology parameters: G3 indicates a severe toxicity, and G4 indicates a life-threatening toxicity. Hematology parameter included: Hemoglobin (Hemo), Total Neutrophils (TN) Absolute, Platelet Count (PC), and White Blood Cell (WBC) Count.	From Baseline (Day 1) until 28 days after the last dose (average of 239 days)