Trastuzumab Plus Docetaxel and Capecitabine For First Line Treatment of Her2-Positive Advanced Gastric Cancer

NCT ID: NCT02004769

Last Updated: 2016-11-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

67 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-11-30

Study Completion Date

2016-06-30

Brief Summary

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Patients with inoperable, locally advanced or recurrent and/or HER2-positive metastatic gastric or gastro-esophageal junction cancer, with no prior treatment for metastatic disease are to be recruited in the study. In the current study, the efficacy and safety of Trastuzumab in combination with Capecitabine/Docetaxel will be evaluated in Chinese patients with HER2 positive advanced or recurrent gastric cancer.60 patients could provide adequate precision rather than controlling type I\&II error. Assuming the target PFS is 6.7m, 60 patients will give 90% CI of (5.5, 8.4). Considering the 5% drop out rate, 65 patients will be enrolled.

Detailed Description

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This is a phase II, multi-center, open label, single arm, interventional study. Patients with HER2-positive metastatic gastric or gastro-esophageal junction adenocarcinoma who have not received prior treatment for metastatic disease will be treated with trastuzumab(8 mg/kg loading dose followed by 6 mg/kg every 3 weeks ),Capecitabine(2000mg/m2d, d1-14,every 3 weeks) and Docetaxel (60mg/m2 every 3 weeks for 6 cycles).All patients will continue to receive trastuzumab and Capecitabine until either disease progression, occurrence of unacceptable toxicity or withdrawal from the study for another reason.Primary endpoints is PFS and secondary endpoints are ORR, OS and Safety.Recruitment period:24 months;PFS follow-up period: 80% PFS events;OS follow-up period: 18 months or 80% OS events, whichever occurs first.

Conditions

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Stomach Neoplasms Neoplasms Metastasis ERBB2 Gene Amplification

Keywords

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Metastatic gastric or gastro-esophageal junction cancer Trastuzumab HER2-positive Capecitabine Docetaxel First-line therapy

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Trastuzumab, Capecitabine, Docetaxel

Trastuzumab(8 mg/kg loading dose followed by 6 mg/kg every 3 weeks) Capecitabine(2000mg/m2d, d1-14,every 3 weeks) Docetaxel (60mg/m2 every 3 weeks for 6 cycles).All patients will continue to receive trastuzumab and Capecitabine until either disease progression, occurrence of unacceptable toxicity or withdrawal from the study for another reason.

Group Type EXPERIMENTAL

Trastuzumab

Intervention Type DRUG

Trastuzumab (Herceptin) will be administered at a loading dose of 8 mg/kg (on day 1) followed by 6mg/kg i.v. infusion every 3 weeks (q3w), until disease progress or intolerable toxicity.

Docetaxel

Intervention Type DRUG

Docetaxel 60mg/m2 (on day 1) every 3 weeks for 6 cycles.

Capecitabine

Intervention Type DRUG

Capecitabine (Xeloda) 2000mg/m2d, d1-14, every 3 weeks until disease progress or intolerable toxicity.

Interventions

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Trastuzumab

Trastuzumab (Herceptin) will be administered at a loading dose of 8 mg/kg (on day 1) followed by 6mg/kg i.v. infusion every 3 weeks (q3w), until disease progress or intolerable toxicity.

Intervention Type DRUG

Docetaxel

Docetaxel 60mg/m2 (on day 1) every 3 weeks for 6 cycles.

Intervention Type DRUG

Capecitabine

Capecitabine (Xeloda) 2000mg/m2d, d1-14, every 3 weeks until disease progress or intolerable toxicity.

Intervention Type DRUG

Other Intervention Names

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Herceptin Taxotere Xeloda

Eligibility Criteria

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Inclusion Criteria

1. Male or female. Age: 18-75 years.
2. Histologically confirmed adenocarcinoma of the stomach or gastro-esophageal junction with inoperable locally advanced or recurrent and/or metastatic disease, not amenable to curative therapy.
3. Measurable disease, according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, assessed using imaging techniques (CT or MRI).
4. HER2 positive tumor (primary tumor or metastasis, HER2 positive as defined by IHC2+ and a confirmatory FISH+ result (HER2:CEP17 ratio ≥2), or by an IHC 3+ result) as assessed by the central laboratory. Accurate and validated assay methods will be used.
5. ECOG Performance status 0-1.
6. Life expectancy of at least 3 months.
7. Signed informed consent.
8. Previous chemotherapy for advanced/metastatic disease (prior adjuvant/neoadjuvant therapy is allowed if at least 6 months has elapsed between completion of adjuvant/neoadjuvant therapy and enrollment into the study; adjuvant/neoadjuvant therapy with docetaxel is not allowed).

9 .Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome (e.g. patients with partial or total gastrectomy can enter the study, but not those with a jejunostomy probe).

10\. Patients with active (significant or uncontrolled) gastrointestinal bleeding.

11\. Residual relevant toxicity resulting from previous therapy (with the exception of alopecia), e.g. neurologic toxicity ≥ grade 2 NCI-CTCAE version 4.0.

12\. Other malignancy within the last 5 years, except for carcinoma in situ of the cervix, or basal cell carcinoma.

13\. Hematologic, Biochemical and Organ Function 14. Neutrophil count \< 1.5 × 109/L, or platelet count \< 100 × 109/L. 15. Serum bilirubin \> 1.5 × upper limit of normal (ULN); or, AST or ALT \> 2.5 × ULN (or \> 5 × ULN in patients with liver metastases); or, alkaline phosphatase \> 2.5 × ULN (or \> 5 × ULN in patients with liver metastases, or \> 10 × ULN in patients with bone but no liver metastases); or albumin \< 25 g/L.

16\. Creatinine clearance \< 60 mL/min.

Exclusion Criteria

1. History of documented congestive heart failure; angina pectoris requiring medication; evidence of transmural myocardial infarction on ECG; poorly controlled hypertension (systolic BP \> 180 mmHg or diastolic BP \> 100 mmHg); clinically significant valvular heart disease; or high risk uncontrollable arrhythmias.
2. Baseline LVEF \< 50% (measured by echocardiography or MUGA).
3. Patients with dyspnea at rest due to complications of advanced malignancy or other disease, or who require supportive oxygen therapy.
4. Patients receiving chronic or high dose corticosteroid therapy. (Inhaled steroids and short courses of oral steroids for anti-emesis or as an appetite stimulant are allowed).
5. Known dihydropyrimidine dehydrogenase (DPD) deficiency.
6. History or clinical evidence of brain metastases.
7. Serious uncontrolled systemic intercurrent illness, e.g. infections or poorly controlled diabetes.
8. Positive serum pregnancy test in women of childbearing potential.
9. Subjects with reproductive potential not willing to use an effective method of contraception.
10. Received any investigational drug treatment within 4 weeks of start of study treatment.
11. Radiotherapy within 4 weeks of start of study treatment (2 week interval allowed if palliative radiotherapy given to bone metastatic site peripherally and patient recovered from any acute toxicity).
12. Major surgery within 4 weeks of start of study treatment, without complete recovery.
13. Patients with known active infection with HIV, HBV, or HCV.
14. Known hypersensitivity to any of the study drugs.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Fudan University

OTHER

Sponsor Role collaborator

307 Hospital of PLA

OTHER

Sponsor Role collaborator

Shandong Tumor Hospital

OTHER

Sponsor Role collaborator

Tongji Hospital

OTHER

Sponsor Role collaborator

West China Hospital

OTHER

Sponsor Role collaborator

Shandong Provincial Hospital

OTHER_GOV

Sponsor Role collaborator

Second Affiliated Hospital of Suzhou University

OTHER

Sponsor Role collaborator

Tianjin Medical University General Hospital

OTHER

Sponsor Role collaborator

Second Affiliated Hospital, School of Medicine, Zhejiang University

OTHER

Sponsor Role collaborator

Sixth Affiliated Hospital, Sun Yat-sen University

OTHER

Sponsor Role collaborator

Nanfang Hospital, Southern Medical University

OTHER

Sponsor Role collaborator

Sun Yat-sen University

OTHER

Sponsor Role lead

Responsible Party

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Ruihua Xu

Vice-president and Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Ruihua Xu, M.D,Ph.D

Role: PRINCIPAL_INVESTIGATOR

Sun Yat-sen University

Locations

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Medical Oncology,Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, China

Site Status

Countries

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China

References

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Sawada N, Ishikawa T, Fukase Y, Nishida M, Yoshikubo T, Ishitsuka H. Induction of thymidine phosphorylase activity and enhancement of capecitabine efficacy by taxol/taxotere in human cancer xenografts. Clin Cancer Res. 1998 Apr;4(4):1013-9.

Reference Type BACKGROUND
PMID: 9563897 (View on PubMed)

Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Ruschoff J, Kang YK; ToGA Trial Investigators. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010 Aug 28;376(9742):687-97. doi: 10.1016/S0140-6736(10)61121-X. Epub 2010 Aug 19.

Reference Type BACKGROUND
PMID: 20728210 (View on PubMed)

Roth AD, Fazio N, Stupp R, Falk S, Bernhard J, Saletti P, Koberle D, Borner MM, Rufibach K, Maibach R, Wernli M, Leslie M, Glynne-Jones R, Widmer L, Seymour M, de Braud F; Swiss Group for Clinical Cancer Research. Docetaxel, cisplatin, and fluorouracil; docetaxel and cisplatin; and epirubicin, cisplatin, and fluorouracil as systemic treatment for advanced gastric carcinoma: a randomized phase II trial of the Swiss Group for Clinical Cancer Research. J Clin Oncol. 2007 Aug 1;25(22):3217-23. doi: 10.1200/JCO.2006.08.0135.

Reference Type BACKGROUND
PMID: 17664469 (View on PubMed)

Thuss-Patience PC, Kretzschmar A, Repp M, Kingreen D, Hennesser D, Micheel S, Pink D, Scholz C, Dorken B, Reichardt P. Docetaxel and continuous-infusion fluorouracil versus epirubicin, cisplatin, and fluorouracil for advanced gastric adenocarcinoma: a randomized phase II study. J Clin Oncol. 2005 Jan 20;23(3):494-501. doi: 10.1200/JCO.2005.02.163.

Reference Type BACKGROUND
PMID: 15659494 (View on PubMed)

Other Identifiers

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ML28670

Identifier Type: -

Identifier Source: org_study_id