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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01924819




Registration number
NCT01924819
Ethics application status
Date submitted
14/08/2013
Date registered
19/08/2013
Date last updated
1/04/2022

Titles & IDs
Public title
Trial of Preoperative Therapy for Gastric and Esophagogastric Junction Adenocarcinoma
Scientific title
A Randomised Phase II/III Trial of Preoperative Chemoradiotherapy Versus Preoperative Chemotherapy for Resectable Gastric Cancer
Secondary ID [1] 0 0
ACTRN12609000035224
Secondary ID [2] 0 0
AG0407GR
Universal Trial Number (UTN)
Trial acronym
TOPGEAR
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Gastric Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Stomach

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Epirubicin + cisplatin + 5-fluorouracil OR epirubicin + cisplatin + capecitabine OR epirubicin + oxaliplatin + capecitabine OR 5-Fluorouracil + leucovorin + oxaliplatin + docetaxel
Treatment: Other - Preoperative chemoradiotherapy
Treatment: Surgery - Gastric resection

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

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


Treatment: Drugs: 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)

Treatment: Other: 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.

Treatment: Surgery: 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.
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Other
Intervention code [3] 0 0
Treatment: Surgery
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall survival
Timepoint [1] 0 0
Up to 5 years
Secondary outcome [1] 0 0
Disease free survival
Timepoint [1] 0 0
Up to 5 years
Secondary outcome [2] 0 0
Pathological response rate
Timepoint [2] 0 0
At time of surgery
Secondary outcome [3] 0 0
Proportion of participants with given grades of toxicities
Timepoint [3] 0 0
Up to 5 years
Secondary outcome [4] 0 0
Surgical complete resection rate (R0)
Timepoint [4] 0 0
At the time of surgery

Eligibility
Key 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 10?
/L, White blood cell count >=3 x 10? /L, Platelet count >=100 x 10? /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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2/Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/09/2009
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/12/2026
Actual
Sample size
Target
Accrual to date
Final
574
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,TAS,VIC,WA
Recruitment hospital [1] 0 0
Calvary Mater Newcastle - Newcastle
Recruitment hospital [2] 0 0
Liverpool Hospital - Sydney
Recruitment hospital [3] 0 0
Nepean Hospital - Sydney
Recruitment hospital [4] 0 0
Prince of Wales Hospital - Sydney
Recruitment hospital [5] 0 0
Royal North Shore Hospital - Sydney
Recruitment hospital [6] 0 0
Royal Prince Alfred Hospital - Sydney
Recruitment hospital [7] 0 0
St George Hospital - Sydney
Recruitment hospital [8] 0 0
Westmead Hospital - Sydney
Recruitment hospital [9] 0 0
The Tweed Hospital - Tweed Heads
Recruitment hospital [10] 0 0
Wollongong Hospital - Wollongong
Recruitment hospital [11] 0 0
Princess Alexandra Hospital - Brisbane
Recruitment hospital [12] 0 0
Flinders Medical Centre - Adelaide
Recruitment hospital [13] 0 0
Royal Hobart Hospital - Hobart
Recruitment hospital [14] 0 0
Launceston General Hospital - Launceston
Recruitment hospital [15] 0 0
Geelong Hospital - Geelong
Recruitment hospital [16] 0 0
Austin Hospital - Melbourne
Recruitment hospital [17] 0 0
Monash Medical Centre - Melbourne
Recruitment hospital [18] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [19] 0 0
St Vincent's Hospital - Melbourne
Recruitment hospital [20] 0 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment postcode(s) [1] 0 0
- Newcastle
Recruitment postcode(s) [2] 0 0
- Sydney
Recruitment postcode(s) [3] 0 0
- Tweed Heads
Recruitment postcode(s) [4] 0 0
- Wollongong
Recruitment postcode(s) [5] 0 0
- Brisbane
Recruitment postcode(s) [6] 0 0
- Adelaide
Recruitment postcode(s) [7] 0 0
- Hobart
Recruitment postcode(s) [8] 0 0
- Launceston
Recruitment postcode(s) [9] 0 0
- Geelong
Recruitment postcode(s) [10] 0 0
- Melbourne
Recruitment postcode(s) [11] 0 0
- Nedlands
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
Auckland
Country [2] 0 0
New Zealand
State/province [2] 0 0
Dunedin
Country [3] 0 0
New Zealand
State/province [3] 0 0
Hamilton

Funding & Sponsors
Primary sponsor type
Other
Name
Australasian Gastro-Intestinal Trials Group
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
National Health and Medical Research Council, Australia
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Trans Tasman Radiation Oncology Group
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
European Organisation for Research and Treatment of Cancer - EORTC
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
NCIC Clinical Trials Group
Address [4] 0 0
Country [4] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01924819
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Trevor Leong, MBBS, MD
Address 0 0
Peter MacCallum Cancer Centre, Australia
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01924819