Efficacy and Safety of Trastuzumab, Capecitabine y Oxaliplatine as Treatment Gastric Cancer Metastatic (HER2)Positive

Stage IV Gastric Cancer With Metastasis Clinical Trial

— HerXO  

Official title:

Phase II Study to Assess the Efficacy and Safety of Trastuzumab in Combination With Xelox as First-line Treatment of Patients With Advanced or Metastatic Gastric Cancer or Gastro-esophageal Junction, (HER2)-Positive.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01503983
• Other study ID #: FUPOCAN-01-11
• Secondary ID: 2011-001231-23
• Status: Completed
• Phase: Phase 2
• First received: December 7, 2011
• Last updated: August 26, 2015
• Start date: August 2011
• Est. completion date: May 2015

Study information

• Verified date: April 2012
• Source: Fundación para el Progreso de la Oncología en Cantabria
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Spanish Agency of Medicines
• Study type: Interventional

Clinical Trial Summary

The objective of the study is assess the efficacy and safety of Trastuzumab in combination with Capecitabine+Oxaliplatin as first-line treatment of patients with advanced or metastatic gastric cancer or gastro-esophageal junction, (HER2)-positive.

Description:

Gastric cancer worldwide is the second tumor incidence (10%). There are significant geographical differences in Spain with an incidence of 15 cases/100,000 per year. Although the incidence and mortality of gastric cancer (GC) have experienced a marked reduction in the past 40 years, this disease remains a leading cause of cancer-related mortality, accounting for more than 870,000 deaths worldwide in the year 2000.

Gastric cancer has a high mortality rate because usually diagnosed when in advanced stage and in many cases has a high relapse rate. Advanced gastric cancer cases are considered to be diagnosed with unresectable disease, either by having locally advanced disease (30% of cases at diagnosis), or having metastatic disease (another 30%) and patients with relapses (60% of resected). Thus, overall around 84% of patients with gastric cancer will have advanced disease.

The only curative treatment so far is surgery. Thanks to early detection and implementation of appropriate surgical techniques, survival has improved in some countries such as Japan and Korea, being the rate of 5-year survival of 47%Over the years, a large number of studies with a single agent chemotherapy has been shown that gastric cancer is a relatively sensitive to chemotherapy. Based on these observations, the trend was the investigation of the combination of chemotherapy agents.

Based on these results FDA and EMEA has approved capecitabine in the treatment of advance gastric cancer combined with platinum.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: May 2015
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients be able to grant a written informed consent or oral consent

• Age =18 years old

• Patients diagnosed with metastatic gastric or gastro-esophageal junction adenocarcinoma (HER2-positive), unresectable and histologically confirmed Measurable disease, following the new RECIST criteria,

• HER2 positive tumors (primary or metastatic) with overexpression HER2 determinated by IHQ +++ (IHQ3+) o IHQ ++ confirmed by FISH/SISH positive (IHQ2+/FISH+)

• ECOG = 2

• Patients of childbearing potential (< 12 months from last menstruation), they have to use effective means of contraception

• Life expectancy more than 3 months

• Adequate renal function: calculated creatinine clearance > 50 mL/min

• Adequate liver function: AST and ALT =2.5 x LSN (5 x LSN with liver metastasis), bilirubin 1,5 x LSN. alkaline phosphatase < 2,5 x LSN (= 5 x LSN with liver metastasis o < 10 x LSN with bone metastases Adequate haematological function: Hb =9 g/dl, neutrophils = 1,5 x 109 /l and platelets 100 x 109 /l.

• Normal Left Ventricle Fraction Ejection , LVEF> 50%

• Every patient should be treated and followed in his / her study site

Exclusion Criteria:

• Prior chemotherapy treatment for advanced/metastatic disease

• Lack of physical integrity of the upper gastrointestinal tract or malabsorption

• Patients with active gastrointestinal bleeding

• Prior chemotherapeutic treatment for advanced / metastatic disease

• Toxicity as a result of prior therapy (except alopecia)., for example.

• Neurology toxicity grade =2NCI-CTCAE

• Patients who received radiotherapy within 4 weeks prior to study treatment.

• Major surgical procedures within 4 weeks prior to treatment without a total surgical recovery.

• Past or current history of other malignancies (within the last 5-2 years prior to treatment start), patients with curatively treated basal cell carcinoma of the skin or in situ carcinoma of the cervix are eligible

• Active and clinically significant cardiovascular disease,

• History or current clinical evidence of brain metastasis

• Patients undergoing transplantation allogenic requiring immunosuppressive treatment

• Moderate or severe renal failure, creatinine clearance < 50 mL/min, calculated by Cockcroft-Gault

• Adequate liver function: bilirubin =1.5 x UL, GOT ( ASAT )/ GPT ( ALAT ) =2,5 LSN. Liver metastasis = 5 x LSN, FA = de 2,5 feces el LSN.

• Adequate haematology function: neutrophils = 1,5 x 109 /l and platelets 100 x 109 /l

• Treatment with sorivudine and the analogous as brivudine.

• Dihydropyrimidine proven dehydrogenase deficiency (DPD).

• Patients who had received any drug, agent or investigational procedure, or who have participated in another research study within 30 days prior to initiation of treatment with study medication.

• Hypersensitivity to any of the study drugs

• Evidence of any other disease, metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or puts the patient at high risk for treatment-related complications

• Patients receiving chronic corticosteroid therapy or high dose (is allowed to use inhaled steroids and cycle short treatment with oral steroids for prevention of emesis or to stimulate appetite)

• Pregnancy and lactation

• Patients of childbearing potential not willing to use effective means of contraception.

• History of psychiatric disorders that the investigator considered clinically significant, causing the patient give informed consent or interfere with compliance with study procedures.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Stage IV Gastric Cancer With Metastasis
• Stomach Neoplasms

Intervention

Drug:
• Trastuzumab
Trastuzumab: 8 mg/kg day 1 followed by 6 mg/kg every 3 weeks (i.v.)
• Capecitabine
Capecitabine: 1000 mg/m2/12h/days 1 - 14 every 3 weeks (v.o.)
• Oxaliplatin
Oxaliplatin: 130 mg/m2 in 2 h, day 1 / (i.v.) /every 3 weeks

Locations

Country	Name	City	State
Spain	Centro Oncológico de Galicia	A Coruña
Spain	Hospital Juan Canalejo	A Coruña
Spain	Hospital de Basurto	Bilbao
Spain	Hospital Arnau de Vilanova de LLeida	Lleida
Spain	Hospital Lucus Augusti de Lugo	Lugo	A Coruña
Spain	Hospital Gregorio Marañon	Madrid
Spain	Hospital La Paz	Madrid
Spain	Hospital de Orense	Orense
Spain	Hospital Universitario Cnetral de Asturias	Oviedo
Spain	Hospital Provincial de Pontevedra	Pontevedra	Vigo
Spain	Hospital Universitario Marqués de Valdecilla	Santander
Spain	Hospital de POVISA	Vigo
Spain	Hospital Xeral Cies	Vigo

Sponsors (1)

Lead Sponsor	Collaborator
Fundación para el Progreso de la Oncología en Cantabria

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival	Overall survival defined as the time from start of treatment until the patient's death	up to 10 Months	No
Secondary	progression free survival	Progression free survival defined as time from start of treatment until date of progression were observed according to RECIST 1.1	5 months	No
Secondary	the time to progression	Time to progression defined as time elapsed since the beginning of treatment until disease progression	5 months	No
Secondary	duration of response	Duration of response defined as the time since the objective complete or partial response until there is disease progression	10 months	No
Secondary	time to response	Time to response, defined as the time from initiation of treatment until objective complete or partial response	10 months	No