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Trial of Preoperative Therapy for Gastric and Esophagogastric Junction Adenocarcinoma (TOPGEAR)

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ClinicalTrials.gov Identifier: NCT01924819
Recruitment Status : Unknown
Verified January 2019 by Australasian Gastro-Intestinal Trials Group.
Recruitment status was:  Recruiting
First Posted : August 19, 2013
Last Update Posted : January 17, 2019
Sponsor:
Collaborators:
National Health and Medical Research Council, Australia
Trans Tasman Radiation Oncology Group
European Organisation for Research and Treatment of Cancer - EORTC
NCIC Clinical Trials Group
Information provided by (Responsible Party):
Australasian Gastro-Intestinal Trials Group

Tracking Information
First Submitted Date  ICMJE August 14, 2013
First Posted Date  ICMJE August 19, 2013
Last Update Posted Date January 17, 2019
Study Start Date  ICMJE September 2009
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 15, 2013)
Overall survival [ Time Frame: Up to 5 years ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 15, 2013)
  • Disease free survival [ Time Frame: Up to 5 years ]
  • Pathological response rate [ Time Frame: At time of surgery ]
  • Proportion of participants with given grades of toxicities [ Time Frame: Up to 5 years ]
  • Surgical complete resection rate (R0) [ Time Frame: At the time of surgery ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Trial of Preoperative Therapy for Gastric and Esophagogastric Junction Adenocarcinoma
Official Title  ICMJE A Randomised Phase II/III Trial of Preoperative Chemoradiotherapy Versus Preoperative Chemotherapy for Resectable Gastric Cancer
Brief Summary Gastric cancer remains a significant global public health problem. Although in developed countries its incidence has dramatically decreased, on a worldwide scale it is still a leading cause of cancer-related deaths. Surgery is the only potentially curative treatment for gastric cancer. Although the survival rates for patients with early stage disease (stage 1A and 1B) are good, this subgroup of patients constitutes only 20% of those undergoing resection. The majority of patients will have locally advanced or metastatic disease at presentation, which has an extremely poor prognosis. The current five-year survival rate for gastric cancer in Western countries is approximately 20-30%, a figure that has improved little over the past 30 years. The intervention arm in TOPGEAR consists of pre-operative chemotherapy, pre-operative chemoradiotherapy, surgery and post-operative chemotherapy. The control arm consists of pre-operative chemotherapy, surgery and post-operative chemotherapy. The primary objective of TOPGEAR is to investigate whether the addition of chemoradiotherapy to chemotherapy is superior to chemotherapy alone in the neoadjuvant setting by improving pathological complete response rates in the first instance, and subsequently overall survival, in patients undergoing adequate surgery (D1+ dissection) for resectable gastric cancer.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Gastric Cancer
Intervention  ICMJE
  • Drug: Epirubicin + cisplatin + 5-fluorouracil OR epirubicin + cisplatin + capecitabine OR epirubicin + oxaliplatin + capecitabine OR 5-Fluorouracil + leucovorin + oxaliplatin + docetaxel

    Epirubicin 50 mg/m2 IV day 1, cisplatin 60 mg/m2 IV day 1, 5-fluorouracil 200 mg/m2/d IV 21 day continuous infusion (ECF chemotherapy).

    Epirubicin 50 mg/m2 IV day 1, Cisplatin 60 mg/m2 IV day 1, Capecitabine (X = Xeloda) 625mg/m2, bid days 1-21 (ECX chemotherapy)

    Epirubicin 50mg/m2 IV day 1, Oxaliplatin (O) 130mg/m2 IV day 1, Capecitabine 625mg/m2, bid days 1-21 (EOX chemotherapy)

    5-Fluorouracil 2600 mg/m² IV 24 h infusion day 1, Leucovorin (L) 200 mg/m² IV day 1, Oxaliplatin 85 mg/m² IV day 1, Docetaxel (T) 50 mg/m² IV day 1 (FLOT chemotherapy)

  • Radiation: Preoperative chemoradiotherapy

    Chemotherapy: Continuous infusional 5-fluorouracil 200mg/m2/day, 7 days per week, throughout the entire period of radiotherapy or capecitabine 825 mg/m2, oral tablet twice daily, days 1-5 of each week of radiotherapy (without weekends).

    Radiotherapy: 45 Gy of radiation in 25 fractions, five days per week for five weeks.

  • Procedure: Gastric resection
    The acceptable resections are a total gastrectomy, a subtotal gastrectomy, and an esophagogastrectomy (Ivor-Lewis esophagogastrectomy for gastroesophageal junction cancers [Siewert Type II and Siewert Type III] invading up to but no more than 2cm of the lower esophagus). The minimum extent of the operation should be a D1+ lymph node dissection but it is recommended that a D2 dissection be performed or a D1+ for gastroesophageal junction cancers requiring an esophagogastrectomy.
Study Arms  ICMJE
  • Experimental: Preoperative chemoradiotherapy

    2 cycles preoperative chemotherapy with: epirubicin + cisplatin + 5-fluorouracil. (5-fluorouracil may be replaced with capecitabine).

    OR epirubicin + oxaliplatin + capecitabine OR 3 cycles of 5-fluorouracil +Leucovorin + oxaliplatin + docetaxel

    5 weeks preoperative chemoradiotherapy.

    Gastric resection.

    3 cycles adjuvant chemotherapy with: epirubicin + cisplatin + 5-fluorouracil. (5-fluorouracil may be replaced with capecitabine).

    OR epirubicin + oxaliplatin + capecitabine OR 4 cycles of 5-fluorouracil +Leucovorin + oxaliplatin + docetaxel

    Interventions:
    • Drug: Epirubicin + cisplatin + 5-fluorouracil OR epirubicin + cisplatin + capecitabine OR epirubicin + oxaliplatin + capecitabine OR 5-Fluorouracil + leucovorin + oxaliplatin + docetaxel
    • Radiation: Preoperative chemoradiotherapy
    • Procedure: Gastric resection
  • Active Comparator: Preoperative chemotherapy

    3 cycles preoperative chemotherapy with: epirubicin + cisplatin + 5-fluorouracil. (5-fluorouracil may be replaced with capecitabine).

    OR epirubicin + oxaliplatin + capecitabine OR 4 cycles of 5-fluorouracil +Leucovorin + oxaliplatin + docetaxel

    Gastric resection.

    3 cycles adjuvant chemotherapy with: epirubicin + cisplatin + 5-fluorouracil. (5-fluorouracil may be replaced with capecitabine) OR epirubicin + oxaliplatin + capecitabine OR 4 cycles of 5-fluorouracil +Leucovorin + oxaliplatin + docetaxel

    Interventions:
    • Drug: Epirubicin + cisplatin + 5-fluorouracil OR epirubicin + cisplatin + capecitabine OR epirubicin + oxaliplatin + capecitabine OR 5-Fluorouracil + leucovorin + oxaliplatin + docetaxel
    • Procedure: Gastric resection
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: January 15, 2019)
620
Original Estimated Enrollment  ICMJE
 (submitted: August 15, 2013)
752
Estimated Study Completion Date  ICMJE December 2020
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically proven adenocarcinoma of the stomach or gastroesophageal junction (GEJ) that is:

    1. Stage IB (T1N1 only, T2N0 not eligible) - IIIC, i.e. T3 - T4 and/or node positive, according to American Joint Committee on Cancer (AJCC) 7th edition.
    2. Considered operable following initial staging investigations (surgeon believes that an R0 resection can be achieved) (GEJ tumours are defined as tumours that arise in the cardia or at the GEJ that do not involve more than 2cm of the lower esophagus, i.e. Siewert Type II and Siewert Type III)
  • Age >=18 years
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Adequate organ function defined as follows:

    1. Bone marrow: Haemoglobin >=90 g/L, Absolute neutrophil count (ANC) >=1.5 x 10⁹ /L, White blood cell count >=3 x 10⁹ /L, Platelet count >=100 x 10⁹ /L
    2. Hepatic: Serum bilirubin <=1.5 x upper limit of normal (ULN), aspartate aminotransferase (AST) and/or alanine transaminase (ALT) <=3.0 x ULN
    3. Renal: Serum creatinine <=0.150 mmol/L, Calculated creatinine clearance >=50 mL/min
  • Disease which can be radically treated with radiotherapy to 45 Gy with standard fractionation
  • Any patient with a history of ischaemic heart disease and abnormal ECG, or who is over 60 years of age should have a pre-treatment evaluation of cardiac function with a multigated acquisition (MUGA) scan or echocardiogram. Patients will only be included if the left ventricular ejection fraction is >=50%.
  • Written informed consent obtained before randomization
  • Negative pregnancy test for women of childbearing potential within 7 days of commencing study treatment. Males and females of reproductive potential must agree to practice adequate contraceptive measures.

Exclusion Criteria:

  • Evidence of metastatic disease
  • Prior chemotherapy or radiotherapy
  • Patients with a past history of cancer in the 5 years before randomization except for the following. Patients with squamous or basal cell carcinoma of the skin that has been effectively treated, and patients with carcinoma in situ of the cervix that has been treated by operation only are eligible, even if they were diagnosed and treated within the 5 years before randomization.
  • Patients with other significant underlying medical conditions that may be aggravated by the study treatment or are not controlled
  • Pregnant or lactating females or female patients of childbearing potential who have not been surgically sterilized or are without adequate contraceptive measures
  • Cardiac failure and other contraindications to epirubicin
  • Patients with impaired gastrointestinal absorption for whatever reason
  • Patients medically unfit for cisplatin chemotherapy due to one or more of the following reasons:

    1. Clinically significant sensorineural hearing impairment (audiometric abnormalities without corresponding clinical deafness will not be regarded as a contraindication to cisplatin)
    2. Severe tinnitus
    3. Renal impairment (GFR <=50ml/min)
    4. Peripheral neuropathy >=grade 2
    5. Inability to tolerate intravenous hydration e.g due to cardiac disease
    6. Co-morbidities (based on clinical judgement by the investigator) that in the view of the investigator would preclude the safe administration of cisplatin.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   New Zealand
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01924819
Other Study ID Numbers  ICMJE AG0407GR
ACTRN12609000035224 ( Registry Identifier: ANZCTR )
U1111-1146-0762 ( Other Identifier: Universal Trial Number )
TROG 08.08 ( Other Identifier: TROG )
22114-40111 ( Other Identifier: EORTC )
GA.1 ( Other Identifier: NCIC CTG )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Australasian Gastro-Intestinal Trials Group
Study Sponsor  ICMJE Australasian Gastro-Intestinal Trials Group
Collaborators  ICMJE
  • National Health and Medical Research Council, Australia
  • Trans Tasman Radiation Oncology Group
  • European Organisation for Research and Treatment of Cancer - EORTC
  • NCIC Clinical Trials Group
Investigators  ICMJE
Study Chair: Trevor Leong, MBBS, MD Peter MacCallum Cancer Centre, Australia
PRS Account Australasian Gastro-Intestinal Trials Group
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP