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

Sponsor

Fundación para el Progreso de la Oncología en Cantabria (Other)

Overall Status

Completed

CT.gov ID

NCT01503983

Collaborator

(none)

Enrollment

Locations

Arm

Duration (Months)

3.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Stage IV Gastric Cancer With Metastasis	Drug: Trastuzumab Drug: Capecitabine Drug: Oxaliplatin	Phase 2

Detailed 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.

Study Design

Study Type:

Interventional

Actual Enrollment :

45 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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.

Study Start Date :

Aug 1, 2011

Actual Primary Completion Date :

Dec 1, 2013

Actual Study Completion Date :

May 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Trastuzumab+Oxaliplatine+capecitabine Patient takes Trastuzumab (initial dose 8 mg/kg and a maintenance dose 6 mg/kg) anda oxaliplatin (dose 130mg/m2) during the first day os cycle and them Capecitabine (dose 2000 mg/m2)during 14 days in cycle of 21 days.	Drug: Trastuzumab Trastuzumab: 8 mg/kg day 1 followed by 6 mg/kg every 3 weeks (i.v.) Other Names: Herceptin Drug: Capecitabine Capecitabine: 1000 mg/m2/12h/days 1 - 14 every 3 weeks (v.o.) Other Names: Xeloda Drug: Oxaliplatin Oxaliplatin: 130 mg/m2 in 2 h, day 1 / (i.v.) /every 3 weeks Other Names: Oxaliplatino

Arm

Intervention/Treatment

Experimental: Trastuzumab+Oxaliplatine+capecitabine

Patient takes Trastuzumab (initial dose 8 mg/kg and a maintenance dose 6 mg/kg) anda oxaliplatin (dose 130mg/m2) during the first day os cycle and them Capecitabine (dose 2000 mg/m2)during 14 days in cycle of 21 days.

Drug: Trastuzumab

Trastuzumab: 8 mg/kg day 1 followed by 6 mg/kg every 3 weeks (i.v.)

Other Names:

Herceptin

Drug: Capecitabine

Capecitabine: 1000 mg/m2/12h/days 1 - 14 every 3 weeks (v.o.)

Other Names:

Xeloda

Drug: Oxaliplatin

Oxaliplatin: 130 mg/m2 in 2 h, day 1 / (i.v.) /every 3 weeks

Other Names:

Oxaliplatino

Outcome Measures

Primary Outcome Measures

Overall Survival [up to 10 Months]
Overall survival defined as the time from start of treatment until the patient's death

Secondary Outcome Measures

progression free survival [5 months]
Progression free survival defined as time from start of treatment until date of progression were observed according to RECIST 1.1
the time to progression [5 months]
Time to progression defined as time elapsed since the beginning of treatment until disease progression
duration of response [10 months]
Duration of response defined as the time since the objective complete or partial response until there is disease progression
time to response [10 months]
Time to response, defined as the time from initiation of treatment until objective complete or partial response

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital Lucus Augusti de Lugo	Lugo	A Coruña	Spain	27003
2	Hospital Provincial de Pontevedra	Pontevedra	Vigo	Spain	36001
3	Hospital Juan Canalejo	A Coruña		Spain	15006
4	Centro Oncológico de Galicia	A Coruña		Spain	15009
5	Hospital de Basurto	Bilbao		Spain	48013
6	Hospital Arnau de Vilanova de LLeida	Lleida		Spain	25198
7	Hospital Gregorio Marañon	Madrid		Spain	28009
8	Hospital La Paz	Madrid		Spain	28046
9	Hospital de Orense	Orense		Spain	32005
10	Hospital Universitario Cnetral de Asturias	Oviedo		Spain	33006
11	Hospital Universitario Marqués de Valdecilla	Santander		Spain	39008
12	Hospital Xeral Cies	Vigo		Spain	36204
13	Hospital de POVISA	Vigo		Spain	36211