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Trial registered on ANZCTR


Registration number
ACTRN12616001112459
Ethics application status
Approved
Date submitted
4/08/2016
Date registered
17/08/2016
Date last updated
28/07/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Study comparing the Efficacy and Safety of FOLFIRINOX ( Fluoropyrimidine, Oxaliplatin and Irinotecan) as Chemotherapy regimen For Resectable Gastric Or Gastroesophageal Junction Cancer to ECF (Cisplatin, Epirubicin and Fluoropyrimidine) as chemotherapy regimen which is the standard treatment
Scientific title
Efficacy and Safety of Folfirinox as Neoadjuvant Chemotherapy for Resectable Gastric or Gastroesophageal junction adenocarcinoma- a run- in pilot followed by Phase 2 comparison between ECF and FOLFIRINOX – FIG study
Secondary ID [1] 289827 0
NIL KNOWN
Universal Trial Number (UTN)
U1111-1185-9846
Trial acronym
FIG
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Resectable gastroesophageal junction adenocarcinoma 299753 0
Resectable gastric adenocarcinoma. 299900 0
Condition category
Condition code
Cancer 299687 299687 0 0
Oesophageal (gullet)
Cancer 299726 299726 0 0
Stomach

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This trial is conducted in 2 steps
In the pilot phase of the trial which is to test for feasability, first 10 patients will be treated with FOLFIRINOX. The feasibility will be defined as the ability of 6 out of 10 pilot patients to undergo curative gastric resection within 18 weeks of starting FOLFIRINOX.
Then we will proceed to phase II of trial where patients will be randomised in 1:1 ratio to standard ECF chemotherapy versus FOLFIRINOX.
Patients will be adequately staged using CT scan chest/ abdomen/ pelvis, Echo, lung functions and laparoscopy to rule out metastatic disease and assess fitness for curative gastric resection. The patients will be discussed at the Statewide Upper GI MDT.
Patients will be consented and have PICC or PORT inserted prior to start of treatment.
Folfirinox Chemotherapy will be administered for six cycles preoperatively (3 months).
A typical cycle will consist of oxaliplatin 85 mg/m2 ; irinotecan 150 mg/m2; leucovorin 50mg. These will be given as a bolus simultaneously followed by 5 FU 2400 mg/m2. 5FU will be a 46-hour continuous infusion, Each cycle is given once every 2 weeks. Patients will be provided with adequate anti emetics and supportive medications as per the institution preference. Growth factors and prophylactic antibiotics are not mandated.
Before each cycle of chemotherapy, a complete blood count, renal and liver function tests will be checked. Patients will be reviewed and assessed every two weeks in the FOLFIRINOX arm to monitor their treatment.
After completing all prescribed cycles of chemotherapy, patients will undergo restaging with CT scan and endoscopy prior to surgery. A minimum interval of 3 weeks will be mandated from last day of chemotherapy to surgery. Majority of the patients will have surgical resection within 3-6 weeks of completing chemotherapy. Post surgery, patients will be followed clinically every 3 months and will have surveillance CT scans at 3, 6, 12, 24 and 36 months or as clinically indicated.
Intervention code [1] 295502 0
Treatment: Drugs
Comparator / control treatment
ECF WILL BE THE CONTROL GROUP WHICH IS CURRENTLY THE STANDARD OF TREATMENT FOR RESECTABLE GASTRIC CANCER
ECF chemotherapy will be given as per the standard doses and schedule with 3 cycles pre-operatively followed by surgery after 4-6 weeks of last dose of chemotherapy. Once the patient recovers from surgery, chemotherapy will be restarted after 4-6 weeks of surgery. 3 cycles will be given post operatively. Each cycle consists of Epirubicin 50 mg/m2 and cisplatin 60mg/m2 on day 1 of each cycle 5FU will be given as an infusion of 1400 mg/m2 over 7 days (equivalent to 200 mg/m2/day) through PICC or port on day 1, 8 and 15 of each cycle. Each cycle will be given intravenously every 3 weeks. Before each cycle of chemotherapy, a complete blood count, renal and liver function tests will be checked. Patients will be reviewed and assessed every 3 weeks in the ECF arm prior to each chemotherapy cycle.
Control group
Active

Outcomes
Primary outcome [1] 299149 0
Progression-free survival (PFS). Progression-free survival (PFS) is the time from the date of randomization to the date of event defined as the first documented progression or death due to any cause. If a patient has not had an event, PFS is censored at the date of last adequate tumor assessment.
Timepoint [1] 299149 0
Post completion of all chemotherapy cycles after surgery, patients will be followed clinically every 3 months and will have surveillance CT scan at 3, 6, 12, 24 and 36 months or as clinically indicated to monitor for PFS.
Secondary outcome [1] 326344 0
1. Ability of patients to proceed to curative gastric resection. The first 10 patients treated will form part of the pilot phase. This refers to the pilot phase of the trial,
Timepoint [1] 326344 0
1.Ability of patients to undergo curative gastric resection within 18 weeks of starting FOLFIRINOX will allow the opening of the randomised phase II portion.
Secondary outcome [2] 326450 0
2. Feasibility of this regimen by assessing toxicities and side effects. Adverse drug reactions and serious adverse drug reactions will be assessed by CTCAE Version 4.0, changes in hematology and chemistry values, specifically those associated with hepatic and renal function; and assessment of physical examinations, vital signs and electrocardiograms
Timepoint [2] 326450 0
2.Before each cycle of chemotherapy, a complete blood count, renal and liver function tests will be checked. Patients will be reviewed and assessed every two weeks in the FOLFIRINOX arm in the clinic on the first day of each cycle and if well, they will proceed with chemotherapy.
Secondary outcome [3] 326451 0
3. Pathological complete response including surgical assessments of down-staging (i.e., tumor diameter, tumor stage, and nodal status). This will be assessed by CT scan and review of the surgical biopsy specimen
Timepoint [3] 326451 0
3. A minimum interval of 3 weeks will be mandated from last day of chemotherapy to assess patient for eligibility for surgery. Ct scan will also be done 3 weeks after last dose of chemotherapy to assess disease response. Majority of the patients will have surgical resection within 4-6 weeks of completing chemotherapy. Post surgery, the specimen will be evaluated for pathological complete response
Secondary outcome [4] 326452 0
4. Overall survival (OS). This is defined as the time from histological diagnosis to date of death.
Timepoint [4] 326452 0
4. patients will be followed clinically every 3 months post last dose of chemotherapy and will have surveillance CT scan at 3, 6, 12, 24 and 36 months or as clinically indicated. Minimum timepoint would be 5 years to see the overall survival rate at 5 years which will be calculated from the time they had their first cycle of chemotherapy.

Eligibility
Key inclusion criteria
1. Patients more than 18 years age and less than 80 years of age
2. Patients with cytological or histological confirmed gastric adenocarcinoma or gastroesophageal junction adenocarcinoma
3. Able to sign Informed Consent
4. World Health Organization (WHO) Performance Status of less than 1
5. Localised gastric cancer or gastroesophageal junction adenocarcinoma considered for curative radical gastrectomy. Eligible patients will have more than or equal to T2 gastric cancer and/ or Siewert III GOJ cancer (cancer of the cardia)
6. Patients must have the following laboratory values:
Hematologic:
“Absolute Neutrophil Count (ANC) more than or equal to 1.5x109/L
“Hemoglobin (Hgb) more than or equal to 9 g/dl
“Platelets (plt) more than or equal to 100x109/L

Biochemistry:
“Potassium within normal limits
“Total calcium (corrected for serum albumin) and Phosphorus within normal limits
“Adequate liver function defined as:
“AST/SGOT and ALT/SGPT less than or equal to 1.5 x Upper Limit of Normal (ULN) if AP more than 2.5 ULN
“Serum bilirubin less than or equal to 1.5 x ULN
“Adequate Kidney function test : Serum creatinine less than or equal to 1.5 x ULN or creatinine clearance more than or equal to 50 ml/min on standard Cockcroft-Gault Equation
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Patients who had previously received cytotoxic chemotherapy or radiotherapy for gastric cancer
2. Uncontrolled cardiac disease
3. Stage 4 disease including peritoneal metastases
4. A history of another major cancer, active infection, chronic diarrhoea, unacceptable blood tests either haematological or biochemistry
5. Patients who are pregnant or breast-feeding.

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)
allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
patients once eligible for the trial as mentioned before in the inclusion criteria, will be randomised in 1:1 ratio to standard ECF chemotherapy versus FOLFIRINOX.

"Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation)"
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1 / Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
The ability of 6 patients to undergo curative gastric resection within 18 weeks of starting FOLFIRINOX will allow opening of the randomised phase II portion of the trial.
The PFS in the ECF arm was 45% at 2 years. A clinically meaningful improvement would be increase to 65% in the experimental arm at 2 years.
Group sample sizes of 96 in Group 1 and 96 in Group 2 achieve 80% power to detect a difference between the group proportions of 0.200. The proportion in Group 1 (the treatment group) is assumed to be 0.4500 under the null hypothesis and 0.6500 under the alternative hypothesis. The proportion in Group 2 (the control group) is 0.4500. The test statistic used is the two-sided Z test with pooled variance. The significance level of the test was targeted at 0.0500. To compare two survival proportion at the end of 2 years, Z test if fine and the sample size calculation is actually based on Z test with pooled variance, not Person chi-square test.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/09/2016
Actual
1/09/2016
Date of last participant enrolment
Anticipated
1/09/2018
Actual
Date of last data collection
Anticipated
1/09/2023
Actual
Sample size
Target
202
Accrual to date
10
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 6368 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [2] 6369 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [3] 6370 0
The Queen Elizabeth Hospital - Woodville
Recruitment hospital [4] 6371 0
Lyell McEwin Hospital - Elizabeth Vale
Recruitment hospital [5] 6372 0
Calvary North Adelaide Hospital - North Adelaide
Recruitment postcode(s) [1] 13918 0
5000 - Adelaide
Recruitment postcode(s) [2] 13919 0
5042 - Bedford Park
Recruitment postcode(s) [3] 13920 0
5011 - Woodville
Recruitment postcode(s) [4] 13921 0
5112 - Elizabeth Vale
Recruitment postcode(s) [5] 13922 0
5006 - North Adelaide

Funding & Sponsors
Funding source category [1] 294212 0
Hospital
Name [1] 294212 0
Royal adelaide hospital
Country [1] 294212 0
Australia
Primary sponsor type
Hospital
Name
Royal Adelaide Hospital
Address
Royal Adelaide Hospital
North Terrace, Adelaide SA 5000
Country
Australia
Secondary sponsor category [1] 293046 0
None
Name [1] 293046 0
NA
Address [1] 293046 0
NA
Country [1] 293046 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295620 0
Central Adelaide Local Health Network
Ethics committee address [1] 295620 0
Level 4, Women’s Health Centre
North Terrace, Adelaide SA
Australia 5000
Ethics committee country [1] 295620 0
Australia
Date submitted for ethics approval [1] 295620 0
29/06/2016
Approval date [1] 295620 0
28/07/2016
Ethics approval number [1] 295620 0
HREC/16/RAH/177

Summary
Brief summary
The primary purpose of this trial is to evaluate the efficacy and safety of FOLFIRINOX chemotherapy for the treatment of gastric or gastroesophageal junction cancer prior to surgery.

Who is it for?
You may be eligible to participate in this trial if you are aged 18 to 80 years and have been diagnosed with gastric adenocarcinoma or gastroesophageal junction adenocarcinoma for which you are scheduled to undergo radical gastrectomy.

Study details
The first ten participants enrolled in this trial will all receive FOLFIRINOX chemotherapy prior to surgery. If six of these participants are able to undergo surgery as planned, then all remaining participants enrolled in this trial will then be randomly allocated computer generated software to receive either FOLFIRINOX chemotherapy prior to surgery, or to receive standard care ECF chemotherapy prior to surgery. Participants in the FOLFIRINOX group will receive a 46 hours continuous infusion of chemotherapy once every 2 weeks for 12 weeks. Participants in the ECF group will receive a 46 hours continuous infusion of chemotherapy every 3 weeks for 12 weeks before surgery and 3 cycles after surgery which will be also be every 3 weeks for 12 weeks . It is anticipated that all participants will then undergo surgery within 3-6 weeks.

Participants will be assessed for side effects and followed-up for up to five years to assess disease progression and survival.

It is hoped that the findings of this trial will establish whether FOLFIRINOX chemotherapy may be a safe and effective alternative to ECF chemotherapy for the pre-surgical treatment of gastric or gastroesophageal junction cancer.
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 987 987 0 0
/AnzctrAttachments/371225-160729 Full SSA Approval Letter.pdf
Attachments [2] 988 988 0 0
/AnzctrAttachments/371225-FIG Protocol V1 17 June 2016.docx

Contacts
Principal investigator
Name 67958 0
Dr Nimit Singhal
Address 67958 0
Royal Adelaide Hospital
Cancer Centre
Level 4, East Wing
North terrace, Adelaide, SA 5000
Country 67958 0
Australia
Phone 67958 0
+61432417954
Fax 67958 0
Email 67958 0
[email protected]
Contact person for public queries
Name 67959 0
Anne Milton
Address 67959 0
Royal Adelaide Hospital
Cancer Centre
Level 4, East Wing
North terrace, Adelaide, SA 5000
Country 67959 0
Australia
Phone 67959 0
+61 8 8222 4765
Fax 67959 0
Email 67959 0
[email protected]
Contact person for scientific queries
Name 67960 0
Nimit Singhal
Address 67960 0
Royal Adelaide Hospital
Cancer Centre
Level 4, East Wing
North Terrace, Adelaide, SA 5000
Country 67960 0
Australia
Phone 67960 0
+61432417954
Fax 67960 0
Email 67960 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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