Clinical trial NCT01924819: Trial of Preoperative Therapy for Gastric and Esophagogastric Junction Adenocarcinoma
Official title: A Randomised Phase II/III Trial of Preoperative Chemoradiotherapy Versus Preoperative Chemotherapy for Resectable Gastric Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Gastric Cancer
Keywords: Gastric cancer
Stomach cancer
Chemoradiotherapy
Surgery
Chemotherapy
Neoadjuvant
Lead sponsor: Australasian Gastro-Intestinal Trials Group
Sponsor class: NETWORK
Collaborators: name: National Health and Medical Research Council, Australia
name: Trans Tasman Radiation Oncology Group
name: European Organisation for Research and Treatment of Cancer - EORTC
name: NCIC Clinical Trials Group
First posted: 2013-08-19
Enrollment: 574
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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: Purpose:

The purpose of this phase II/III clinical trial is to determine if pre-operative chemoradiotherapy improves overall survival in participants with resectable gastric cancer.

Trial details:

Participants will be randomised to receive either pre-operative chemotherapy or pre-operative chemoradiotherapy. The will undergo surgery and then receive further post-operative chemotherapy. Participants will be followed up for 5 years after treatment.

Eligibility 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.

Primary outcomes:
measure: Overall survival
timeFrame: Up to 5 years
Secondary outcomes:
measure: Disease free survival
timeFrame: Up to 5 years
measure: Pathological response rate
timeFrame: At time of surgery
measure: Proportion of participants with given grades of toxicities
timeFrame: Up to 5 years
measure: Surgical complete resection rate (R0)
timeFrame: At the time of surgery
Other outcomes:
Locations:
city: Newcastle
country: Australia
facility: Calvary Mater Newcastle
state: New South Wales
city: Sydney
country: Australia
facility: Chris O Brien Lifehouse
state: New South Wales
city: Sydney
country: Australia
facility: Liverpool Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Nepean Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Prince of Wales Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Sydney
country: Australia
facility: St George Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Tweed Heads
country: Australia
facility: The Tweed Hospital
state: New South Wales
city: Wollongong
country: Australia
facility: Wollongong Hospital
state: New South Wales
city: Brisbane
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Flinders Medical Centre
state: South Australia
city: Hobart
country: Australia
facility: Royal Hobart Hospital
state: Tasmania
city: Launceston
country: Australia
facility: Launceston General Hospital
state: Tasmania
city: Geelong
country: Australia
facility: Geelong Hospital
state: Victoria
city: Melbourne
country: Australia
facility: Austin Hospital
state: Victoria
city: Melbourne
country: Australia
facility: Monash Medical Centre
state: Victoria
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Melbourne
country: Australia
facility: St Vincent's Hospital
state: Victoria
city: Melbourne
country: Australia
facility: Sunshine Hospital (Western Health)
state: Victoria
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital
state: Western Australia
city: Brasschaat
country: Belgium
facility: AZ Klina
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
city: La Louvière
country: Belgium
facility: Hospital De Jolimont
city: Leuven
country: Belgium
facility: U.Z Leuven Campus Gasthuisberg
city: Oostende
country: Belgium
facility: AZ Damiaan
city: Turnhout
country: Belgium
facility: AZ Turnhout- Campus Sint Elisabeth
city: Verviers
country: Belgium
facility: Centre Hospitalier Peltzer- La Tourelle
city: Vancouver
country: Canada
facility: BCCA - Vancouver Centre
state: British Columbia
city: Winnipeg
country: Canada
facility: Cancer Care Manitoba
state: Manitoba
city: Barrie
country: Canada
facility: Royal Victoria Regional Health Centre
state: Ontario
city: Kingston
country: Canada
facility: Cancer Centre of Southeastern Ontario at Kingston General Hospital
state: Ontario
city: Kitchener
country: Canada
facility: Grand River Regional Cancer Center, Kitchener
state: Ontario
city: London
country: Canada
facility: London Regional Cancer Program
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Health Research Institute
state: Ontario
city: Toronto
country: Canada
facility: Odette Cancer Centre, Sunnybrook Hospital
state: Ontario
city: Toronto
country: Canada
facility: UHN - Princess Margaret Hospital
state: Ontario
city: Montreal
country: Canada
facility: Hopital Maisonneuve-Rosemont
state: Quebec
city: Montreal
country: Canada
facility: Hospital Notre-Dame
state: Quebec
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Sherbrooke
country: Canada
facility: Centre hospitalier universitaire de Sherbrooke
state: Quebec
city: Regina
country: Canada
facility: Allan Blair Cancer Centre
state: Saskatchewan
city: Saskatoon
country: Canada
facility: Saskatoon Cancer Centre
state: Saskatchewan
city: Hradec Kralove
country: Czechia
facility: Charles University Hospital
city: Avignon
country: France
facility: Institut Sainte Catherine
city: Besancon
country: France
facility: CHRU de Besancon Hopital Jean Minjoz
city: Montbeliard
country: France
facility: Centre Hospitalier de Belfort Montbeliard site du Mittan
city: Strasbourg
country: France
facility: Centre Paul Strauss
city: München
country: Germany
facility: Klinikum der Universitaet Muenchen - Campus Grosshadern
state: Bavaria
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Auckland
country: New Zealand
facility: Auckland Hospital
city: Dunedin
country: New Zealand
facility: Dunedin Hospital
city: Hamilton
country: New Zealand
facility: Waikato Hospital
city: Ljubljana
country: Slovenia
facility: The Institute of Oncology
city: L'Hospitalet De Llobregat
country: Spain
facility: ICO L Hospitalet Hospital Duran i Reynals (Institut Catala D Oncologia)
state: Barcelona
city: Badalona
country: Spain
facility: Institut Catala d Oncologia - ICO Badalona - Hospital Germans Trias i Pujol
city: Barcelona
country: Spain
facility: Vall D Hebron University Hospital
city: Valencia
country: Spain
facility: Hospital Clinico Universitario De Valencia
Study officials:
affiliation: Peter MacCallum Cancer Centre, Australia
name: Trevor Leong, MBBS, MD
role: STUDY_CHAIR
References: