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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 : 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 (TROG)
European Organisation for Research and Treatment of Cancer - EORTC
NCIC Clinical Trials Group
Information provided by (Responsible Party):
Australasian Gastro-Intestinal Trials Group

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.

Condition or disease Intervention/treatment Phase
Gastric Cancer 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 Phase 2 Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 620 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomised Phase II/III Trial of Preoperative Chemoradiotherapy Versus Preoperative Chemotherapy for Resectable Gastric Cancer
Study Start Date : September 2009
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Stomach Cancer

Arm Intervention/treatment
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

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.

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

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)


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.




Primary Outcome Measures :
  1. Overall survival [ Time Frame: Up to 5 years ]

Secondary Outcome Measures :
  1. Disease free survival [ Time Frame: Up to 5 years ]
  2. Pathological response rate [ Time Frame: At time of surgery ]
  3. Proportion of participants with given grades of toxicities [ Time Frame: Up to 5 years ]
  4. Surgical complete resection rate (R0) [ Time Frame: At the time of surgery ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01924819


Contacts
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Contact: Christine Aiken topgear@ctc.usyd.edu.au

Locations
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Australia, New South Wales
Calvary Mater Newcastle Recruiting
Newcastle, New South Wales, Australia
Liverpool Hospital Recruiting
Sydney, New South Wales, Australia
Nepean Hospital Recruiting
Sydney, New South Wales, Australia
Prince of Wales Hospital Recruiting
Sydney, New South Wales, Australia
Royal North Shore Hospital Recruiting
Sydney, New South Wales, Australia
Royal Prince Alfred Hospital Recruiting
Sydney, New South Wales, Australia
St George Hospital Recruiting
Sydney, New South Wales, Australia
Westmead Hospital Recruiting
Sydney, New South Wales, Australia
The Tweed Hospital Recruiting
Tweed Heads, New South Wales, Australia
Wollongong Hospital Recruiting
Wollongong, New South Wales, Australia
Australia, Queensland
Princess Alexandra Hospital Recruiting
Brisbane, Queensland, Australia
Australia, South Australia
Flinders Medical Centre Recruiting
Adelaide, South Australia, Australia
Australia, Tasmania
Royal Hobart Hospital Recruiting
Hobart, Tasmania, Australia
Launceston General Hospital Recruiting
Launceston, Tasmania, Australia
Australia, Victoria
Geelong Hospital Recruiting
Geelong, Victoria, Australia
Austin Hospital Active, not recruiting
Melbourne, Victoria, Australia
Monash Medical Centre Recruiting
Melbourne, Victoria, Australia
Peter MacCallum Cancer Centre Recruiting
Melbourne, Victoria, Australia
St Vincent's Hospital Recruiting
Melbourne, Victoria, Australia
Australia, Western Australia
Sir Charles Gairdner Hospital Recruiting
Nedlands, Western Australia, Australia
Royal Perth Hospital Withdrawn
Perth, Western Australia, Australia
New Zealand
Auckland Hospital Recruiting
Auckland, New Zealand
Christchurch Hospital Withdrawn
Christchurch, New Zealand
Dunedin Hospital Completed
Dunedin, New Zealand
Waikato Hospital Completed
Hamilton, New Zealand
Sponsors and Collaborators
Australasian Gastro-Intestinal Trials Group
National Health and Medical Research Council, Australia
Trans-Tasman Radiation Oncology Group (TROG)
European Organisation for Research and Treatment of Cancer - EORTC
NCIC Clinical Trials Group
Investigators
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Study Chair: Trevor Leong, MBBS, MD Peter MacCallum Cancer Centre, Australia

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Responsible Party: Australasian Gastro-Intestinal Trials Group
ClinicalTrials.gov Identifier: NCT01924819     History of Changes
Other Study ID Numbers: 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 )
First Posted: August 19, 2013    Key Record Dates
Last Update Posted: January 17, 2019
Last Verified: January 2019
Keywords provided by Australasian Gastro-Intestinal Trials Group:
Gastric cancer
Stomach cancer
Chemoradiotherapy
Surgery
Chemotherapy
Neoadjuvant
Additional relevant MeSH terms:
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Stomach Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Cisplatin
Docetaxel
Capecitabine
Oxaliplatin
Fluorouracil
Epirubicin
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors