T- XELOX in HER2-positive Stage III Gastric Cancer After D2 Gastrectomy

Gastric Cancer Clinical Trial

Official title:

Trastuzumab Plus XELOX for HER2-positive Stage III Gastric Cancer After D2 Gastrectomy：Prospective Observational Study.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02250209
• Other study ID #: CGOG20130101005
• Status: Recruiting
• Phase: Phase 2
• First received: September 24, 2014
• Last updated: September 24, 2014
• Start date: July 2014
• Est. completion date: December 2017

Study information

• Verified date: September 2014
• Source: Chinese PLA General Hospital
• Contact: Guanghai Dai, PHD
• Phone: 13801232381
• Email: daigh60[@]sohu.com
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The objective of this study is to assess the clinical efficacy and safety of trastuzumab plus XELOX for treatment of HER2-positive Stage III Gastric Cancer After D2 Gastrectomy.

Description:

Gastric cancer is the second leading cause of cancer death worldwide. Highest incidence rate is observed in Eastern Asia.

D2 gastrectomy has been established as a standard surgical procedure. While recurrence rate after resection is still high.

The CLASSIC study showed that Xelox regimen after D2 gastrectomy improves 3-year disease-free survival compared with surgery only. But patients with late stage still have poor prognosis according to subgroup analysis and our retrospective study.

HER2 is an important biomarker and key driver of tumorigenesis in 7-34% gastric cancers. The ToGA study showed that trastuzumab, a monoclonal antibody that targets HER2, plus chemotherapy improved overall survival(16.0m vs 11.8m) in patients with HER2-positive advanced gastric or gastro-oesophageal junction cancer.

Based on previous experiences of trastuzumab in adjunctive therapy of breast cancer and ACTS/CLASSIC/ToGA studies, we suppose that trastuzumab plus XELOX as adjunctive treatment may benefit patients with HER2-positive Stage III gastric cancer after D2 Gastrectomy.

According to the above, we do this single-arm research to assess the clinical efficacy and safety of trastuzumab plus XELOX for treatment of HER2-positive Stage III Gastric Cancer After D2 Gastrectomy.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: December 2017
• Est. primary completion date: June 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Signed informed-consent form.

2. Aged 18-80 years.

3. Had partial or total D2 gastrectomy and achieved R0 resection.

4. Histologically confirmed gastric or gastro-oesophageal junction adenocarcinoma,mucinous adenocarcinoma ,signet-ring cell carcinoma

5. Pathologic Stage III (IIIA-C).

6. HER2-positive: (IHC 3+ or IHC 2+ and FISH positive).

7. Patients must have received no preoperative chemotherapy or radiation therapy.

8. Eastern Cooperative Oncology Group (ECOG) performance status 0-2 .

9. Adequate liver/bone marrow function.Blood and biochemical parameters;

10. Compliant, and can be followed up regularly.

Exclusion Criteria:

1. Patients who do not meet the Inclusion Criteria.

2. Pregnant or breast-feeding female, or not willing to take contraception measures during study.

3. Serious infection requiring antibiotics intervention during recruitment.

4. Allergic to study drug or with metabolism disorder.

5. Histologically confirmed small cell carcinoma of the stomach?gastric neuroendocrine carcinoma or others.

6. Uncontrolled brain metastasis or mental illness.

7. Organ transplant recipients (Autologous transplantation of bone marrow and peripheral stem cell transplantation included).

8. Congestive heart failure, uncontrolled cardiac arrhythmia, etc.

9. With severe hepatic/kidney/respirator/disease,or chronic disease like uncontrolled diabetes,hypertension,etc.

10. with other malignant tumors.

11. Can be followed up or obey protocol.

12. Ineligible by the discretion of the investigator.

Study Design

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

Related Conditions & MeSH terms

• Gastric Cancer
• Stomach Neoplasms

Intervention

Drug:
• Trastuzumab
Trastuzumab is given by intravenous infusion at 440mg on day 0every 3 weeks. Number of cycles: 14~16 cycles.
• Capecitabine
Capecitabine 800~1000 mg/m² is given orally twice a day for 14 days followed by a 1-week rest. Number of cycles: 8 cycles.
• Oxaliplatin
Oxaliplatin is given by intravenous infusion at 130 mg/m2 on day 1 every 3 weeks. Number of cycles: 8 cycles.

Locations

Country	Name	City	State
China	Chinese PLA General Hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Chinese PLA General Hospital

Country where clinical trial is conducted

China, 

References & Publications (12)

Bang YJ, Kim YW, Yang HK, Chung HC, Park YK, Lee KH, Lee KW, Kim YH, Noh SI, Cho JY, Mok YJ, Kim YH, Ji J, Yeh TS, Button P, Sirzén F, Noh SH; CLASSIC trial investigators. Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLAS — View Citation

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, Rüschoff J, Kang YK; ToGA Trial Investigators. Trastuzumab in combination with chemotherapy versus chemotherapy — View Citation

Dai GH, Shi Y, Chen L, Lv YL, Zhong M. Trastuzumab combined with docetaxel-based regimens in previously treated metastatic gastric cancer patients with HER2 over-expression. Hepatogastroenterology. 2012 Nov-Dec;59(120):2439-44. — View Citation

Gravalos C, Jimeno A. HER2 in gastric cancer: a new prognostic factor and a novel therapeutic target. Ann Oncol. 2008 Sep;19(9):1523-9. doi: 10.1093/annonc/mdn169. Epub 2008 Apr 25. Review. — View Citation

Hofmann M, Stoss O, Shi D, Büttner R, van de Vijver M, Kim W, Ochiai A, Rüschoff J, Henkel T. Assessment of a HER2 scoring system for gastric cancer: results from a validation study. Histopathology. 2008 Jun;52(7):797-805. doi: 10.1111/j.1365-2559.2008.03 — View Citation

Okines AF, Thompson LC, Cunningham D, Wotherspoon A, Reis-Filho JS, Langley RE, Waddell TS, Noor D, Eltahir Z, Wong R, Stenning S. Effect of HER2 on prognosis and benefit from peri-operative chemotherapy in early oesophago-gastric adenocarcinoma in the MA — View Citation

Piccart-Gebhart MJ, Procter M, Leyland-Jones B, Goldhirsch A, Untch M, Smith I, Gianni L, Baselga J, Bell R, Jackisch C, Cameron D, Dowsett M, Barrios CH, Steger G, Huang CS, Andersson M, Inbar M, Lichinitser M, Láng I, Nitz U, Iwata H, Thomssen C, Lohris — View Citation

Sasako M, Sakuramoto S, Katai H, Kinoshita T, Furukawa H, Yamaguchi T, Nashimoto A, Fujii M, Nakajima T, Ohashi Y. Five-year outcomes of a randomized phase III trial comparing adjuvant chemotherapy with S-1 versus surgery alone in stage II or III gastric — View Citation

Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M, Baselga J, Norton L. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J M — View Citation

Smith I, Procter M, Gelber RD, Guillaume S, Feyereislova A, Dowsett M, Goldhirsch A, Untch M, Mariani G, Baselga J, Kaufmann M, Cameron D, Bell R, Bergh J, Coleman R, Wardley A, Harbeck N, Lopez RI, Mallmann P, Gelmon K, Wilcken N, Wist E, Sánchez Rovira — View Citation

Tanner M, Hollmén M, Junttila TT, Kapanen AI, Tommola S, Soini Y, Helin H, Salo J, Joensuu H, Sihvo E, Elenius K, Isola J. Amplification of HER-2 in gastric carcinoma: association with Topoisomerase IIalpha gene amplification, intestinal type, poor progno — View Citation

Terashima M, Kitada K, Ochiai A, Ichikawa W, Kurahashi I, Sakuramoto S, Katai H, Sano T, Imamura H, Sasako M; ACTS-GC Group. Impact of expression of human epidermal growth factor receptors EGFR and ERBB2 on survival in stage II/III gastric cancer. Clin Ca — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	3-year disease-free survival (DFS)	Defined as the time from study treatment to the time of recurrence of the original gastric cancer, development of a new gastric cancer, or death from any cause.	Measure at every 6 weeks (every 2 cycles)	No
Secondary	Overall survival	Measure of time from study treatment to patient's death or lost to follow-up.	up to 3 years	No
Secondary	Safety and tolerability	Percentage of patients who experience adverse events during this study.	up to 18 month	Yes
Secondary	Prognostic value of biomarkers	assessment of the relationship between biomarker status and prognosis	up to 3 years	No