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Study to Evaluate Safety and Efficacy of Perioperative Chemotherapy With Docetaxel, Cisplatin and Capecitabine (DCX) in Patients With Gastro-esophageal Cancer (DCXAIOCHARITE)

Primary Purpose

Gastric Cancer, Esophageal Cancer

Status
Unknown status
Phase
Phase 2
Locations
Germany
Study Type
Interventional
Intervention
Docetaxel, Cisplatin, Capecitabine
Sponsored by
Charite University, Berlin, Germany
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Gastric Cancer focused on measuring adenocarcinoma of the stomach, gastro-esophageal junction or distal esophagus, gastric cancer, esophageal cancer, gastro-esophageal junction, docetaxel, capecitabine, cisplatin, perioperative chemotherapy

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Signed and dated consent
  • Age between minimum 18 and maximum 75 years
  • Primary diagnosis of histologically proven adenocarcinoma of the stomach, the gastro-esophageal junction or an adenocarcinoma of the lower third of the esophagus
  • Stage II-III, which is in TNM-staging: T3-4, N0-3, M0 or T2, N1-3, M0 or T1, N2, M0. (equivalent to clinical staging uT3-4NXM0, uT1-2N+M0)
  • Intended curative resection according to evaluation of an experienced surgeon
  • Karnofsky-performance-index > 70%
  • Negative pregnancy blood test at screening but not earlier than 72 hours prior to start of chemotherapy for women with child bearing potential
  • Adequate haematologic function and liver and renal function: neutrophils > 1,5 x 109/L; thrombocytes > 100 x 109/L; haemoglobin > 10 g/dl, creatinine clearance > 60 ml/min (calculated according to Cockroft and Gault), total bilirubin < 1,0 x UNL; AST and ALT < 1,5 x UNL, AP < 2,5 x UNL
  • Complete staging within 3 weeks prior to start of treatment (CT-scan of thorax and abdomen, endosonography, gastroscopy)
  • Ability to keep appointments and follow the study protocol
  • By CT-scan, endoscopy or endosonography measurable or evaluable disease

Exclusion Criteria:

  • Former therapy of gastro-esophageal cancer (operation, chemo- or radiotherapy)
  • Diagnosis of another cancer in the last 5 years prior to study entry which has not been cured by operation only (exception in-situ-carcinoma of the cervix or cured non-melanomatose skin cancer)
  • Known dihydropyrimidine-dehydrogenase (DPD)-deficiency
  • Known contraindication to the planned chemotherapeutics
  • Presence of distant metastases

  • Anamnestic known serious disease or other concomitant diseases that affect participation in this study, such as:

    • Instable cardiac disease: symptomatic heart failure, symptomatic coronary artery disease, ventricular cardiac arrhythmia not well controlled with medication, myocardial infarction or resuscitation within 6 month before study
    • Active infection necessitating systemic therapy or uncontrolled infection
    • Interstitial lung diseases (for example: pneumonitis or fibrosis of the lung) and indication for interstitial lung disease in chest x-ray or CT-scan respectively
    • Active inflammatory bowel disease or other bowel diseases which provoke chronic diarrhea (defined as > 4 bowel movements per day)
    • Neurological or psychiatric disease including dementia, epilepsy or untreated, symptomatic brain metastases
    • Limited hearing ability
  • Presence of upper GI obstruction, leading to inability to swallow ground tablets
  • Presence of acute or chronic systemic infection
  • Presence of a bowel obstruction within the last 30 days
  • Pregnant or lactating women or women with child bearing potential and men without adequate contraception (high effective contraception, defined as Pearl Index < 1) like birth control pill, hormone spiral, hormone implant, transdermal patch, a combination of two barrier methods (condom and diaphragm), realized sterilization or sexual abstinence during the study and at least for 3 months after the last infusion
  • Any other situation which may lead to an unacceptable high risk for the patient, when he participates in the study
  • Parallel treatment in another clinical study or prior participation in this study
  • Treatment with any other therapy against the tumor or any parallel radiation
  • Parallel treatment with Sorivudine or an chemically related substance like for example Brivudin
  • Symptomatic peripheral neuropathy NCI-CTCAE degree > 2
  • Intolerance to the study medication or their galencic ingredients or against 5-FU
  • Detention in a psychiatric unit or imprisonment (AMG §40 Abs. 1 Nr. 4)

Sites / Locations

  • HELIOS-Klinik Bad Saarow
  • Klinik für Hämatologie, Onkologie und Tumorimmunologie, Charite Campus Buch
  • Medizinische Klinik mit Schwerpunkt Gastroenterologie, Infektiologie und Rheumatologie, Charite Campus Benjamin-Franklin
  • Medizinische Klinik mit Schwerpunkt Hämatologie und Onkologie, Charite Campus Virchow Klinikum
  • Klinik für Innere Medizin Abteilung Hämatologie/Onkologie, Städtisches Klinikum Dessau
  • Universitätsklinik und Poliklinik für Innere Medizin IV, Martin Luther Universität Halle-Wittenberg
  • II. Medizinische Klinik und Poliklinik, Universitätsklinikum Schleswig-Holstein Campus Kiel
  • Internistische Onkologie/ Hämatologie, Städtisches Krankenhaus St. Georg
  • 3. Medizinische Klinik, Onkologisches Zentrum, Universitätsklinikum Mannheim

Outcomes

Primary Outcome Measures

R0-resection rate

Secondary Outcome Measures

Remission rate according to diagnostic imaging techniques
Pathological remission rate
Operative and postoperative complication rate
Resectability rate
Rate of local recurrences and metastasis
Toxicity
30-day mortality
Overall survival
Overall survival rate
Event free survival rate

Full Information

First Posted
March 19, 2009
Last Updated
August 4, 2011
Sponsor
Charite University, Berlin, Germany
Collaborators
Roche Pharma AG, Sanofi
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1. Study Identification

Unique Protocol Identification Number
NCT00865982
Brief Title
Study to Evaluate Safety and Efficacy of Perioperative Chemotherapy With Docetaxel, Cisplatin and Capecitabine (DCX) in Patients With Gastro-esophageal Cancer
Acronym
DCXAIOCHARITE
Official Title
Multicenter, Open Lable Phase II Study to Evaluate the Safety and Efficacy of a Perioperative Chemotherapy With Docetaxel, Cisplatin and Capecitabine in Patients With Gastric Adenocarcinoma, Adenocarcinoma of the Gastro-esophageal Junction or the Distal Esophagus
Study Type
Interventional

2. Study Status

Record Verification Date
August 2011
Overall Recruitment Status
Unknown status
Study Start Date
September 2008 (undefined)
Primary Completion Date
September 2014 (Anticipated)
Study Completion Date
September 2015 (Anticipated)

3. Sponsor/Collaborators

Name of the Sponsor
Charite University, Berlin, Germany
Collaborators
Roche Pharma AG, Sanofi

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
In this study, patients with adenocarcinoma of the stomach, gastro-esophageal junction or the distal esophagus who seem operable with curative intent according to oncological and surgical assessment are treated with 3 preoperative cycles of DCX (Docetaxel, Cisplatin, Capecitabine) followed by surgical resection, followed by 3 postoperative cycles of DCX.
Detailed Description
Perioperative chemotherapy has been shown to significantly improve the R0 resection rate, the disease free survival and the overall survival in patients with adenocarcinoma of the distal esophagus, the gastro-esophageal junction and the stomach. Therefore perioperative chemotherapy is the new therapeutic standard (Cunningham NEJM 2006, MRC, Lancet 2002, Boige ASCO 2007). The best evaluated regime is the combination of Epirubicin, Cisplatin and 5-FU (ECF) (Cunningham, NEJM 2007). Cisplatin and 5-FU seem to be the most important components forming the backbone of this regime (Boige ASCO 2007). Docetaxel is a new and highly active agent in gastric cancer. In a randomized phase II study the dual combination of Docetaxel and 5-FU seemed to show similar activity as ECF, administered as first line palliative treatment (Thuss-Patience, JCO, 2005). The three drug combination Docetaxel, Cisplatin, 5-FU has significantly superior efficacy than a combination of Cisplatin und 5-FU, superior quality of life and significantly superior overall survival (Van Cutsem, JCO 2007). It has been shown that Capecitabine the oral prodrug of 5-FU is similarly active as 5-FU and can replace intravenous 5-FU in combination with Cisplatin in the treatment of gastric cancer. Capecitabine therefore is FDA approved for gastric cancer (Cunningham, ASCO 2006, Kang ASCO 2006). It seems reasonable to optimize perioperative chemotherapy by including modern chemotherapeutics. The old standard ECF may be improved by integrating Docetaxel und Capecitabine. By adding Docetaxel to the Cisplatin / flouropyrimidin backbone the efficacy of the regime may be improved. The replacement of 5-FU by Capecitabine may improve patients´ convenience and possibly effectiveness of the combination. Therefore the 3 drug combination of Docetaxel, Cisplatin, Capecitabin (DCX) seems to be a highly promising regime regarding effectiveness and convenience. In this study patients with adenocarcinoma of the stomach, gastro-esophageal junction or the distal esophagus who seem operable with curative intent according to oncological and surgical assessment are treated with 3 preoperative cycles of DCX followed by surgical resection, followed by 3 postoperative cycles of DCX. The first application of study medication has to be within 21 days of tumour assessment. There will be 3 preoperative cycles every 3 weeks. The experimental perioperative regime evaluated in this study will be Docetaxel/Cisplatin/Capecitabine DCX (75/ 60/ 1875 mg/m2).The operation will be performed 3 to 6 weeks after the end of the third preoperative chemotherapy cycle (counted from day 21 of cycle 3). Postoperative chemotherapy will start within 6 - 12 weeks after the operation. 3 weeks after the end of the last chemotherapy the final investigation (end of study visit) will be done.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gastric Cancer, Esophageal Cancer
Keywords
adenocarcinoma of the stomach, gastro-esophageal junction or distal esophagus, gastric cancer, esophageal cancer, gastro-esophageal junction, docetaxel, capecitabine, cisplatin, perioperative chemotherapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Docetaxel, Cisplatin, Capecitabine
Intervention Description
3 preoperative cycles with Docetaxel 75 mg/m² d1 Cisplatin 60 mg/m² d1 Capecitabine 1875 mg/m²/day d1-14 repeated every 3 weeks followed by resection and 3 postoperative cycles with Docetaxel 75 mg/m² d1 Cisplatin 60 mg/m² d1 Capecitabine 1875 mg/m²/day d1-14 repeated every 3 weeks.
Primary Outcome Measure Information:
Title
R0-resection rate
Time Frame
After 3 cycles of preoperative chemotherapy (3 month)
Secondary Outcome Measure Information:
Title
Remission rate according to diagnostic imaging techniques
Time Frame
After 3 cycles of preoperative chemotherapy (3 month)
Title
Pathological remission rate
Time Frame
After 3 cycles of preoperative chemotherapy (3 month)
Title
Operative and postoperative complication rate
Time Frame
Within 30 days after surgery
Title
Resectability rate
Time Frame
After 3 cycles of preoperative chemotherapy (3 month)
Title
Rate of local recurrences and metastasis
Title
Toxicity
Title
30-day mortality
Time Frame
After date of surgery
Title
Overall survival
Title
Overall survival rate
Time Frame
1,2,3 and 5 years
Title
Event free survival rate

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Signed and dated consent Age between minimum 18 and maximum 75 years Primary diagnosis of histologically proven adenocarcinoma of the stomach, the gastro-esophageal junction or an adenocarcinoma of the lower third of the esophagus Stage II-III, which is in TNM-staging: T3-4, N0-3, M0 or T2, N1-3, M0 or T1, N2, M0. (equivalent to clinical staging uT3-4NXM0, uT1-2N+M0) Intended curative resection according to evaluation of an experienced surgeon Karnofsky-performance-index > 70% Negative pregnancy blood test at screening but not earlier than 72 hours prior to start of chemotherapy for women with child bearing potential Adequate haematologic function and liver and renal function: neutrophils > 1,5 x 109/L; thrombocytes > 100 x 109/L; haemoglobin > 10 g/dl, creatinine clearance > 60 ml/min (calculated according to Cockroft and Gault), total bilirubin < 1,0 x UNL; AST and ALT < 1,5 x UNL, AP < 2,5 x UNL Complete staging within 3 weeks prior to start of treatment (CT-scan of thorax and abdomen, endosonography, gastroscopy) Ability to keep appointments and follow the study protocol By CT-scan, endoscopy or endosonography measurable or evaluable disease Exclusion Criteria: Former therapy of gastro-esophageal cancer (operation, chemo- or radiotherapy) Diagnosis of another cancer in the last 5 years prior to study entry which has not been cured by operation only (exception in-situ-carcinoma of the cervix or cured non-melanomatose skin cancer) Known dihydropyrimidine-dehydrogenase (DPD)-deficiency Known contraindication to the planned chemotherapeutics Presence of distant metastases Anamnestic known serious disease or other concomitant diseases that affect participation in this study, such as: Instable cardiac disease: symptomatic heart failure, symptomatic coronary artery disease, ventricular cardiac arrhythmia not well controlled with medication, myocardial infarction or resuscitation within 6 month before study Active infection necessitating systemic therapy or uncontrolled infection Interstitial lung diseases (for example: pneumonitis or fibrosis of the lung) and indication for interstitial lung disease in chest x-ray or CT-scan respectively Active inflammatory bowel disease or other bowel diseases which provoke chronic diarrhea (defined as > 4 bowel movements per day) Neurological or psychiatric disease including dementia, epilepsy or untreated, symptomatic brain metastases Limited hearing ability Presence of upper GI obstruction, leading to inability to swallow ground tablets Presence of acute or chronic systemic infection Presence of a bowel obstruction within the last 30 days Pregnant or lactating women or women with child bearing potential and men without adequate contraception (high effective contraception, defined as Pearl Index < 1) like birth control pill, hormone spiral, hormone implant, transdermal patch, a combination of two barrier methods (condom and diaphragm), realized sterilization or sexual abstinence during the study and at least for 3 months after the last infusion Any other situation which may lead to an unacceptable high risk for the patient, when he participates in the study Parallel treatment in another clinical study or prior participation in this study Treatment with any other therapy against the tumor or any parallel radiation Parallel treatment with Sorivudine or an chemically related substance like for example Brivudin Symptomatic peripheral neuropathy NCI-CTCAE degree > 2 Intolerance to the study medication or their galencic ingredients or against 5-FU Detention in a psychiatric unit or imprisonment (AMG §40 Abs. 1 Nr. 4)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Peter Thuss-Patience, Dr. med.
Organizational Affiliation
Charite University, Berlin, Germany
Official's Role
Study Chair
Facility Information:
Facility Name
HELIOS-Klinik Bad Saarow
City
Bad Saarow
Country
Germany
Facility Name
Klinik für Hämatologie, Onkologie und Tumorimmunologie, Charite Campus Buch
City
Berlin
Country
Germany
Facility Name
Medizinische Klinik mit Schwerpunkt Gastroenterologie, Infektiologie und Rheumatologie, Charite Campus Benjamin-Franklin
City
Berlin
Country
Germany
Facility Name
Medizinische Klinik mit Schwerpunkt Hämatologie und Onkologie, Charite Campus Virchow Klinikum
City
Berlin
Country
Germany
Facility Name
Klinik für Innere Medizin Abteilung Hämatologie/Onkologie, Städtisches Klinikum Dessau
City
Dessau
Country
Germany
Facility Name
Universitätsklinik und Poliklinik für Innere Medizin IV, Martin Luther Universität Halle-Wittenberg
City
Halle (Saale)
Country
Germany
Facility Name
II. Medizinische Klinik und Poliklinik, Universitätsklinikum Schleswig-Holstein Campus Kiel
City
Kiel
Country
Germany
Facility Name
Internistische Onkologie/ Hämatologie, Städtisches Krankenhaus St. Georg
City
Leipzig
Country
Germany
Facility Name
3. Medizinische Klinik, Onkologisches Zentrum, Universitätsklinikum Mannheim
City
Mannheim
Country
Germany

12. IPD Sharing Statement

Citations:
PubMed Identifier
22734012
Citation
Thuss-Patience PC, Hofheinz RD, Arnold D, Florschutz A, Daum S, Kretzschmar A, Mantovani-Loffler L, Bichev D, Breithaupt K, Kneba M, Schumacher G, Glanemann M, Schlattmann P, Reichardt P, Gahn B. Perioperative chemotherapy with docetaxel, cisplatin and capecitabine (DCX) in gastro-oesophageal adenocarcinoma: a phase II study of the Arbeitsgemeinschaft Internistische Onkologie (AIO)dagger. Ann Oncol. 2012 Nov;23(11):2827-2834. doi: 10.1093/annonc/mds129. Epub 2012 Jun 24.
Results Reference
derived

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Study to Evaluate Safety and Efficacy of Perioperative Chemotherapy With Docetaxel, Cisplatin and Capecitabine (DCX) in Patients With Gastro-esophageal Cancer

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