Clinical trial NCT02931890: Multicentric Randomised Trial for Resectable Gastric Cancer
Official title: A Multicentre Randomised Phase II Trial of Neo-adjuvant Chemotherapy Followed by Surgery vs. Neo-adjuvant Chemotherapy and Subsequent Chemoradiotherapy Followed by Surgery vs. Neo-adjuvant Chemoradiotherapy Followed by Surgery in Resectable Gastric Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Gastric Cancer
Keywords: gastric cancer
radiotherapy
chemoradiotherapy
Lead sponsor: The Netherlands Cancer Institute
Sponsor class: OTHER
First posted: 2016-10-13
Enrollment: 207
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: The CRITICS-II trial aims to identify the optimal preoperative regimen in resectable gastric cancer by comparing three investigational treatment arms: chemotherapy vs. chemotherapy and subsequent chemoradiotherapy vs. chemoradiotherapy. The rationale behind this trial design is based on the following concepts:

* Preoperative treatment is associated with better patient compliance than postoperative regimens
* Preoperative treatment increases the likelihood of disease downsizing/downstaging and radical R0 resections
* Preoperative paclitaxel/carboplatin-based concurrent chemoradiotherapy and DOC chemotherapy are effective, feasible and safe regimens


Eligibility criteria: Inclusion Criteria:

* TNM 8th ed stage IB-IIIC gastric cancer (histologically proven); tumour bulk has to be in the stomach but may involve gastro-oesophageal junction
* WHO \< 2
* Age ≥ 18 yrs
* Resectable adenocarcinoma of the stomach or gastro-oesophageal junction
* No prior abdominal radiotherapy
* Haematology: Hb ≥5.0 mmol/l; leukocytes≥3.0x109/l, neutrophils ≥1.5x109/l, thrombocytes ≥100x109/l
* Renal function: serum creatinine ≤1.25x ULN, creatinine clearance ≥ 50 ml/min (calculated by Cockcroft and Gault formula) Liver function: total bilirubin ≤1.5x ULN, alkaline phosphatase and ASAT/ALAT ≤ 3x ULN
* At staging laparoscopy (mandatory) obtained biopsies of suspected peritoneal lesions and/or substantial free peritoneal fluid if any should be pathologically proven tumor negative
* Written informed consent
* Expected adequacy of follow-up
* Caloric intake≥1500 kcal/day, verified by a dietician before registration.
* if caloric intake is \< 1500 kcal/day or if bodyweight has decreased \> 10% over the last 6 months or \> 5% over the last month, dietary intervention such as oral nutritional support or enteral tube feeding is mandatory

Exclusion Criteria:

* T1N0 disease (assessed by endoscopic ultrasound)
* Distant metastases
* Inoperable patients; due to technical surgery-related factors or general condition
* Previous malignancy, except adequately treated non-melanoma skin cancer or in-situ cancer of the cervix uteri; in case of a previous other malignancy with a disease-free period≥5 years, inclusion can be accepted after consultation of the principal investigator
* Solitary functioning kidney that will be within the radiation field
* Major surgery within 4 weeks prior to study treatment start, or lack of complete recovery from the effects of major surgery
* Uncontrolled (bacterial) infections
* Significant concomitant diseases preventing the safe administration of study drugs or likely to interfere with study assessments
* Uncontrolled angina pectoris, cardiac failure or clinically significant arrhythmias
* Continuous use of immunosuppressive agents equivalent to \>10 mg daily prednison
* Concurrent use of the antiviral agent sorivudine or chemically related analogues, such as brivudine
* Neurotoxicity \> CTC grade 1
* Pregnancy or breast feeding
* Patients (M/F) with reproductive potential not implementing adequate contraceptive measures
* Gastric or gastro-esophageal stent within radiation field

Primary outcomes:
measure: Event-Free survival
timeFrame: 1 year
Secondary outcomes:
measure: Time to Event (events: local recurrence, regional recurrence, local-regional recurrence or progression, distant recurrence, or death from any cause)
timeFrame: 1 year
measure: Time to recurrence (events: local recurrence, regional recurrence, local-regional recurrence or progression, distant recurrence)
timeFrame: 1 year
measure: Toxicity
timeFrame: 1 year
Other outcomes:
Locations:
city: Leeuwarden
country: Netherlands
facility: Medisch Centrum Leeuwarden
state: Friesland
city: Leeuwarden
country: Netherlands
facility: Radiotherapeutisch Instituut Friesland
state: Friesland
city: Sittard-Geleen
country: Netherlands
facility: Zuyderland Medisch Centrum
state: Limburg
city: Venlo
country: Netherlands
facility: Viecuri Medisch Centrum
state: Limburg
city: Deurne
country: Netherlands
facility: Elkerliek
state: Noord Brabant
city: Eindhoven
country: Netherlands
facility: Catharina Ziekenhuis
state: Noord Brabant
city: Eindhoven
country: Netherlands
facility: Maxima Medisch Centrum
state: Noord Brabant
city: Geldrop
country: Netherlands
facility: St. Anna Zorggroep
state: Noord Brabant
city: Helmond
country: Netherlands
facility: Elkerliek
state: Noord Brabant
city: Tilburg
country: Netherlands
facility: Instituut Verbeeten
state: Noord Brabant
city: Uden
country: Netherlands
facility: Bernhoven
state: Noord Brabant
city: Veldhoven
country: Netherlands
facility: Maxima Medisch Centrum
state: Noord Brabant
city: Hoofddorp
country: Netherlands
facility: Spaarne Gasthuis
state: Noord-Holland
city: Almelo
country: Netherlands
facility: Ziekenhuisgroep Twente
state: Overijssel
city: Deventer
country: Netherlands
facility: Deventer Ziekenhuis
state: Overijssel
city: Enschede
country: Netherlands
facility: Medisch Spectrum Twente
state: Overijssel
city: Leiden
country: Netherlands
facility: Leids Universitair Medisch Centrum
state: Zuid Holland
city: Delft
country: Netherlands
facility: Reinier de Graaf Gasthuis
state: Zuid-Holland
city: 's-Hertogenbosch
country: Netherlands
facility: Jeroen Bosch Ziekenhuis
city: Amsterdam
country: Netherlands
facility: Netherlands Cancer Instituut
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum
city: Arnhem
country: Netherlands
facility: Rijnstate
city: Den Haag
country: Netherlands
facility: HAGA ziekenhuis
city: Ede
country: Netherlands
facility: Ziekenhuis Gelderse Vallei
city: Groningen
country: Netherlands
facility: Universitair Medisch Centrum Groningen
city: Nieuwegein
country: Netherlands
facility: Ziekenhuis St Antonius
city: Tilburg
country: Netherlands
facility: Elisabeth Tweesteden Ziekenhuis
city: Utrecht
country: Netherlands
facility: Universitair Medisch Centrum Utrecht
Study officials:
affiliation: The Netherlands Cancer Institute
name: Marcel Verheij, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Slagter AE, Jansen EPM, van Laarhoven HWM, van Sandick JW, van Grieken NCT, Sikorska K, Cats A, Muller-Timmermans P, Hulshof MCCM, Boot H, Los M, Beerepoot LV, Peters FPJ, Hospers GAP, van Etten B, Hartgrink HH, van Berge Henegouwen MI, Nieuwenhuijzen GAP, van Hillegersberg R, van der Peet DL, Grabsch HI, Verheij M. CRITICS-II: a multicentre randomised phase II trial of neo-adjuvant chemotherapy followed by surgery versus neo-adjuvant chemotherapy and subsequent chemoradiotherapy followed by surgery versus neo-adjuvant chemoradiotherapy followed by surgery in resectable gastric cancer. BMC Cancer. 2018 Sep 10;18(1):877. doi: 10.1186/s12885-018-4770-2.