NCT01924819|Active Not RecruitingPhase 2DMC

Trial of Preoperative Therapy for Gastric and Esophagogastric Junction Adenocarcinoma

TOPGEAR

A Randomised Phase II/III Trial of Preoperative Chemoradiotherapy Versus Preoperative Chemotherapy for Resectable Gastric Cancer

Australasian Gastro-Intestinal Trials Group ClinicalTrials.gov

Compare

6 other identifiers

AG0407GRACTRN12609000035224U1111-1146-0762TROG 08.0822114-40111GA.1

Study Type

interventional

Target

574

Locations

10 countries

Sites

Timeline

RegisteredAug 2013

StartedSep 2009

CompletionDec 2026

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 Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

574

participants targeted

Target at P75+ for phase_2 gastric-cancer

Timeline

8mo left

Started Sep 2009

Longer than P75 for phase_2 gastric-cancer

Geographic Reach

10 countries

59 active sites

Status

active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

17.3 years study duration

Study Progress96%

Sep 2009Dec 2026

Study Start

First participant enrolled

September 1, 2009

Completed

4 years until next milestone

First Submitted

Initial submission to the registry

August 14, 2013

Completed

5 days until next milestone

First Posted

Study publicly available on registry

August 19, 2013

Completed

13.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2026

Expected

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2026

Last Updated

March 4, 2025

Status Verified

August 1, 2024

Enrollment Period

17.3 years

First QC Date

August 14, 2013

Last Update Submit

February 28, 2025

Conditions

Gastric Cancer

Keywords

Gastric cancerStomach cancerChemoradiotherapySurgeryChemotherapyNeoadjuvant

Outcome Measures

Primary Outcomes (1)

Overall survival
The interval from the date of randomisation to the date of death from any cause, or the date last known alive.
Up to 5 years

Secondary Outcomes (4)

Disease free survival
Up to 5 years
Pathological response rate
At time of surgery
Proportion of participants with given grades of toxicities
Up to 5 years
Surgical complete resection rate (R0)
At the time of surgery

Study Arms (2)

Preoperative chemoradiotherapy

EXPERIMENTAL

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 + docetaxelRadiation: Preoperative chemoradiotherapyProcedure: Gastric resection

Preoperative chemotherapy

ACTIVE COMPARATOR

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

Epirubicin + cisplatin + 5-fluorouracil OR epirubicin + cisplatin + capecitabine OR epirubicin + oxaliplatin + capecitabine OR 5-Fluorouracil + leucovorin + oxaliplatin + docetaxelDRUG

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)

Also known as: Epirubicin hydrochloride, Pharmorubicin, Ellence, Platinol, 5-FU, Adrucil, Carac, Efudex. Efudix, Xeloda, Eloxatin, Folinic acid, 5-formyl tetrahydrofolic acid, Citrovorum Factor, Taxotere, Docetere

Preoperative chemoradiotherapyPreoperative chemotherapy

Preoperative chemoradiotherapyRADIATION

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.

Preoperative chemoradiotherapy

Gastric resectionPROCEDURE

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.

Preoperative chemoradiotherapyPreoperative chemotherapy

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

Histologically proven adenocarcinoma of the stomach or gastroesophageal junction (GEJ) that is:
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.
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:
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
Hepatic: Serum bilirubin \<=1.5 x upper limit of normal (ULN), aspartate aminotransferase (AST) and/or alanine transaminase (ALT) \<=3.0 x ULN
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.

You may not qualify if:

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:
Clinically significant sensorineural hearing impairment (audiometric abnormalities without corresponding clinical deafness will not be regarded as a contraindication to cisplatin)
Severe tinnitus
Renal impairment (GFR \<=50ml/min)
Peripheral neuropathy \>=grade 2
Inability to tolerate intravenous hydration e.g due to cardiac disease
Co-morbidities (based on clinical judgement by the investigator) that in the view of the investigator would preclude the safe administration of cisplatin.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Australasian Gastro-Intestinal Trials Grouplead
National Health and Medical Research Council, Australiacollaborator
Trans Tasman Radiation Oncology Groupcollaborator
European Organisation for Research and Treatment of Cancer - EORTCcollaborator
NCIC Clinical Trials Groupcollaborator

Study Sites (59)

Calvary Mater Newcastle

Newcastle, New South Wales, Australia

Location

Chris O Brien Lifehouse