Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

The Role of Postoperative Cycles in the Perioperative Chemotherapy for Gastric Cancer (STOPEROPCHEM)

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2013 by Medical University of Lublin
Sponsor:
Collaborator:
St Johns' Oncology Center in Lublin
Information provided by (Responsible Party):
Tomasz Skoczylas, Medical University of Lublin
ClinicalTrials.gov Identifier:
NCT01787539
First received: February 6, 2013
Last updated: NA
Last verified: February 2013
History: No changes posted
  Purpose

Taking into account the substantial doubts concerning the potential benefit of postoperative part in the perioperative chemotherapy regimen we designed a study assessing value of this approach in gastric cancer. To improve compliance with a protocol regimen of this aggressive combined therapy we replaced tested in the MAGIC trial ECF regimen with more effective and better tolerable EOX chemotherapy regimen. The value of postoperative three-cycle EOX regimen will be tested in patients with locoregionally advanced gastric cancer with positive pathological response to preoperative three-cycle EOX chemotherapy regimen. The patients will be randomized to the postoperative chemotherapy or to the follow-up arm.


Condition Intervention Phase
Gastric Cancer
Drug: Postoperative Chemotherapy
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: The Role of Postoperative Chemotherapy Cycles in the Combined Modality Therapy of Gastric Cancer With Perioperative Chemotherapy and Surgery in Pathological Responders

Resource links provided by NLM:


Further study details as provided by Medical University of Lublin:

Primary Outcome Measures:
  • cancer free and overall survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • overall and severe toxicity rate [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
  • chemotherapy related mortality [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
  • the rate of dose reduction for chemotherapeutics [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
  • the rate of chemotherapy cessation [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]

Other Outcome Measures:
  • quality of life [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment: 180
Study Start Date: February 2013
Estimated Study Completion Date: February 2022
Estimated Primary Completion Date: February 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Complete Perioperative Chemotherapy

Preoperative chemotherapy with EOX regimen: Epirubicin with intravenous bolus at a dose of 50 mg/m2 an on day 1; Oxaliplatin with intravenous infusion during a 2-hour period at a dose of 130 mg/m2; Capecitabine administrated orally at a twice daily dose of 625 mg /m2 during 21 days. Treatment cycles will be repeated every 3 weeks.

Surgery: total or subtotal gastrectomy with D2 lymph node dissection. The surgical resection will be conducted 4-6 weeks after preoperative chemotherapy.

Postoperative chemotherapy will be administrated in patients with tumor regression grade 0, 1, 2 randomized to perioperative chemotherapy and will be initiated 6 to 12 weeks after surgery with the same regimen as in the preoperative part.

Drug: Postoperative Chemotherapy

Postoperative chemotherapy with EOX regimen: Epirubicin with intravenous bolus at a dose of 50 mg/m2 an on day 1; Oxaliplatin with intravenous infusion during a 2-hour period at a dose of 130 mg/m2; Capecitabine administrated orally at a twice daily dose of 625 mg /m2 during 21 days. Treatment cycles will be repeated every 3 weeks.

Postoperative chemotherapy will be administrated in patients with tumor regression grade 0, 1, 2 randomized to perioperative chemotherapy and will be initiated 6 to 12 weeks after surgery.

No Intervention: Preoperative Chemotherapy

Preoperative chemotherapy with EOX regimen: Epirubicin with intravenous bolus at a dose of 50 mg/m2 an on day 1; Oxaliplatin with intravenous infusion during a 2-hour period at a dose of 130 mg/m2; Capecitabine administrated orally at a twice daily dose of 625 mg /m2 during 21 days. Treatment cycles will be repeated every 3 weeks.

Surgery: total or subtotal gastrectomy with D2 lymph node dissection. The surgical resection will be conducted 4-6 weeks after preoperative chemotherapy.

Patients with tumor regression grade 0, 1, 2 randomized to preoperative chemotherapy will not undergo postoperative chemotherapy and will be followed-up.


Detailed Description:

The MAGIC trial, also considered the "milestone" study, definitely proved that neoadjuvant chemotherapy improves the outcome of patients with locally advanced gastric cancer. Resection was considered curative in 79% under combination therapy versus in 69% of only operated patients (P = 0.02), 2-year survival rates were 50 and 41%, and 5-year-survival rates were 36 and 23% (P = 0.009), respectively. The substantial weak point of the MAGIC trial remains the fact that only about 40% of the patients received the full dosage of scheduled postoperative chemotherapy, mainly due to intolerance or toxicity reasons.

The noninferiority in relation to survival of capecitabine to 5-FU in triplet regimens for the treatment of patients with advanced esophagogastric cancer was demonstrated in the large multicenter randomized phase III, REAL-2 study, including 1002 patients. Capecitabine has overcome the doubts concerning the potential efficacy of oral drug administration in patients with gastric carcinoma, especially in relation to those patients who have undergone partial or total gastrectomy. The same study demonstrated the noninferiority of oxaliplatin versus cisplatin in advanced gastric cancer and confirmed the acceptable tolerability profile of this third-generation platinum analogue. It was anticipated that the use of these newer agents as components of triplet regimens would reduce toxicity and thereby render an alternative to the standard ECF combination easier to handle as a consequence of replacing the cisplatin component with oxaliplatin, replacing the infusional 5-fluorouracil component with oral capecitabine in EOX regimen. Furthermore, achieving a median overall survival time of 11.2 months, the EOX regimen appeared to be more active than ECF (median overall survival time, 9.9 months), with the higher 1-year survival rate 47% vs 38%, respectively. Compared with the ECF regimen, EOX was associated with significantly lower rates of grade 3 or 4 neutropenia and grade 2 alopecia, but significantly higher rates of grade 3 or 4 lethargy, diarrhea, and peripheral neuropathy. Based on the results of the REAL study, EOX is therefore tolerable, and at least as active as ECF. This modified regimen could therefore be considered to be a new standard treatment and may be an appropriate reference regimen for future studies in advanced gastric cancer.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • histopathologically confirmed gastric cancer
  • potentially resectable, local or locoregional cancer with clinical staging cT2-4aN0-3M0. A clinical assessment of location, resectability and staging will be performed based on endoscopy, barium swallow, endoscopic ultrasound, multidetector computed tomography and diagnostic laparoscopy with cytology washing.
  • medically fit to undergo a major abdominal surgery and in general condition allowing to tolerate long-lasting chemotherapy (Karnofsky Performance Status ≥70, ECOG 0-1)

Exclusion Criteria:

  • Pregnancy or breast feeding.
  • Diagnosed other malignancy and/or chemotherapy administrated within the last 5 years
  • Gastric remnant cancer;
  • Early Gastric Cancer;
  • Irresectable or disseminated cancer with distant organ metastases and/or peritoneal spreading and/or positive cytology washing
  • Poor performance status measured by Karnofsky index < 60 or ECOG < 1
  • Clinically important active systemic disease: unstable diabetes, circulatory failure of NYHA III or IV, unstable arterial hypertension, unstable coronary heart disease, recent heart infarct or brain insult within the last 6 months, severe COPD, peripheral neuropathy of grade 2-4;
  • Severe hematological abnormalities: HGB < 10.0 gm/dL and/or neutropenia < 1500 /mm3; PLT < 100 000 /mm3.
  • Severe renal dysfunction requiring peritoneal dialysis, hemodialysis or hemofiltration or oliguria <20ml/h.
  • Severe liver dysfunction: acute or chronic hepatitis, liver cirrhosis, liver failure, abnormal liver testing: ALAT or ASPAT or ALP >2.5 - 5.0 × upper limit; total bilirubin >2 x upper limit.
  • Concommitant infection
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01787539

Contacts
Contact: Tomasz Skoczylas, MD, PhD +48 81 5328810 tomskocz@yahoo.com

Locations
Poland
Second Department of General & Gastrointestinal Surgery & Surgical Oncology of the Alimentary Tract, Medical University of Lublin Recruiting
Lublin, Lubelskie, Poland, 20-081
Contact: Tomasz Skoczylas, MD, PhD    +48 81 5328810    tomskocz@yahoo.com   
Principal Investigator: Grzegorz Wallner, Professor         
Principal Investigator: Andrzej Dąbrowski, Professor         
Sub-Investigator: Witold Zgodziński, MD, PhD         
Sub-Investigator: Marek Majewski, MD, PhD         
Sub-Investigator: Krzysztof Zinkiewicz, MD, PhD         
Sub-Investigator: Witold Krupski, Professor         
Sub-Investigator: Justyna Szumiło, Professor         
Sub-Investigator: Jadwiga Sierocińska-Sawa, MD, PhD         
St. John's Cancer Center Recruiting
Lublin, Lubelskie, Poland, 20-090
Contact: Tomasz Kubiatowski, MD, PhD    +48 81 7477511 ext 129      
Principal Investigator: Elżbieta Starosławska, MD, PhD         
Principal Investigator: Tomasz Kubiatowski, MD, PhD         
Sub-Investigator: Bożena Kukiełka-Budny, MD, PhD         
Sponsors and Collaborators
Medical University of Lublin
St Johns' Oncology Center in Lublin
Investigators
Principal Investigator: Tomasz Skoczylas, MD, PhD Second Department of General & Gastrointestinal Surgery & Surgical Oncology of the Alimentary Tract, Medical University of Lublin
Principal Investigator: Grzegorz Wallner, Professor Second Department of General & Gastrointestinal Surgery & Surgical Oncology of the Alimentary Tract, Medical University of Lublin
Principal Investigator: Elżbieta Starosławska, MD, PhD St Johns' Oncology Center in Lublin
Principal Investigator: Tomasz Kubiatowski, MD, PhD St Johns' Oncology Center in Lublin
  More Information

No publications provided

Responsible Party: Tomasz Skoczylas, MD, PhD, Medical University of Lublin
ClinicalTrials.gov Identifier: NCT01787539     History of Changes
Other Study ID Numbers: GC-COMB-0254/275/2012-MUL, GC-0254/282/2011/275/2012-MUL
Study First Received: February 6, 2013
Last Updated: February 6, 2013
Health Authority: Poland: Ethics Committee

Keywords provided by Medical University of Lublin:
gastric cancer
perioperative chemotherapy
combined modality therapy
gastrectomy

Additional relevant MeSH terms:
Stomach Neoplasms
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Neoplasms
Neoplasms by Site
Stomach Diseases

ClinicalTrials.gov processed this record on November 25, 2014