FOxTROT Trial Overview

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FOxTROT Trial Overview Powered By Docstoc
					                              FOxTROT - Fluoropyrimidine, Oxaliplatin and Targeted Receptor
                              pre-Operative Therapy for high risk colon cancer
                              Protocol Development Group: Dion Morton, Gina Brown, David Ferry, Richard Gray, Laura Magill, Phil Quirke,
                              Matt Seymour, Bryan Warren

FOXTROT trial objectives:                                                                  Panitumumab in FOxTROT                                                          Eligibility criteria
►FOxTROT is a Multi-centre RCT to determine:                                               • Data from the OPUS and CRYSTAL trials showed that anti-EGFR                   Exclusion criteria:
                                                                                           monoclonal antibodies are effective only in patients with wildtype K-Ras               • Rectal tumours
                                                                                           expression                                                                             • Distant metastases
   • Whether giving the 1st 6 weeks of chemotherapy pre-operatively compared
                                                                                                                                                                                  • Serious medical morbidity
   with the standard 24-weeks post-operatively reduces the risk of disease                 • ~ 60% colorectal cancers are WT for K-Ras expression
   recurrence at 2 years?
                                                                                           • All patients will be screened at trial entry for K-Ras expression

   • Whether adding panitumumab to preoperative chemotherapy of KRAS                       • Tumour analysis available within 1 week
   wildtype tumours produces a measurable increase in anti-tumour efficacy as              • K-Ras WT tumours randomised across all 4 arms of the trial
   measured by tumour shrinkage.
                                                                                                                                                                          Trial design                          A) OxMdG                       OxMdG
                                                                                                                                                                                                                                   S                      A
                                                                                           • K-Ras mutant tumours NOT eligible for p-mab, randomised between pre-                                                   x3                           x9
                                                                                           plus post-op vs post-op chemotherapy only.                                                                             (6wks  )
                                                                                                                                                                                                                                             (18 weeks)
                                                                                           • Centres can elect to not randomise into the panitumumab arms of                                                      B) OxMdG         G           OxMdG
Rationale behind the trial                                                                 FOxTROT                                                                        Operable                                    x3           E             x9       B
                                                                                                                                                                        Colon Cancer                                (6wks)         R         (18 weeks)
   • Neoadjuvant therapy has been shown to improve success rates in:                                                                                                                                                               Y
                                                                                                                                                                        T4 or high risk
      -   rectal cancer, stomach cancer, oesophageal cancer                                                                                                                T3 by CT                             Pan (6wks)
                                                                                                           FOxTROT Randomisation Pathway                                    criteria;
   • Improvements in chemotherapy for colorectal cancer:                                                                                                                Fit for surgery
                                                                                                                                                                                                               S                   C) OxMdG x12           C
       -    Fluoropyrimidine/Oxaliplatin chemotherapy achieves high                                Introduce FOxTROT idea                                                and chemo                                                  (24 weeks)
       (> 50%) response in advanced disease De Gramont                                            Obtain consent for K-RAS test
       -     Low risk of progression during chemotherapy (14% at 12                               Give patient FOxTROT P.I.S.                  Fax consent form to
                                                                                                                                                                                                               G                   D) OxMdG x12
   weeks in FOCUS)                               Seymour ASCO 2005                                                                               pathology dept                                                                                           D
                                                                                                                                                                                                               E                    (24 weeks)
                                                                                                      Min 24 hr
       -     Short (6-week) pre-operative course, toxicity acceptable &                                                                                                                                        R               Pan
   unlikely to delay surgery                     André NEJM 2004                                                                                                                                               Y             (6wks)
                                                                                                  Obtain consent for FOxTROT                  Send biopsy block to
      -   Panitumumab shown to be effective in patients with wildtype                             Optional consent for ± P-mab                FOxTROT Trial Lab
   KRAS tumours                             Van Cutsem ASCO 2008                               Randomise for pre vs post-op OxMdG
                                                                                                        Give main P.I.S   .

   • Improved CT scan staging                                                                                                               Send KRAS test result to    Primary Outcome
       -  Pilot cohort study of 102 scans, 2 independent, blinded                                                    Fax test result &       FOxTROT study office
                                                                                                                     allocation to key                                     • Disease free recurrence at 2 years
   observers                                                                                         Usually ≥7
       -  distinguished low risk from high risk                                                      days                worker &                                                 – pre+post-op vs post-op therapy (A+B vs C+D)
       -  only 1 (T2) over-staged                   G Brown, I Swift                                                     pharmacy              If KRAS wildtype &
                                                                                                                                              consent, randomise to
                                                                                                                                                    ± P-mab                • Impact of panitumumab on tumour down-staging
                                                                                                    Start FOxTROT treatment
                                                                                                         (chemotherapy ±                                                          - pathological depth of extramural invasion (A vs B)
                                                                                                    panitumumab or surgery)
FOxTROT – 2 stage trial
                                                                                                                                                                       Trial status
 Pilot stage – 150 patients will be randomised and will be used to:
                                                                                                                                                                         • FOXTROT has been funded by CRUK and approved by the West Glasgow MREC
      • Establish safety & tolerability of neoadjuvant therapy
                                                                                                                                                                         • 14 centres fully open to recruitment
      • Validate & fine-tune radiological staging criteria                             Eligibility criteria
      • Only OxMdG will be prescribed in the pilot phase                                                                                                                          - A further 61 centres signed up and awaiting approval
                                                                                       Inclusion criteria:
                                                                                                                                                                                  - 5 radiology and 2 pathology training days held so far
                                                                                             • Histologically proven colon cancer
 Phase III – Additional 900 patients will be randomised:                                     • CT scan indicating poor prognosis:                                                 - TRICC application funded
      • Panitumumab arm retention if safe and tolerated in pilot                                    - T4 or T3 ‘bad’ tumours                                                      - Radiology audit in place at selected centres
      • Implement standardised radiological staging and histology                                   (T3 bad = depth of invasion ≥5mm muscularis propria)                 Contact trial coordinator, Dr Laura Magill, to sign up:
reporting                                                                                           - NX, M0
                                                                                                                                                                                 Tel: 0121 415 9105
                                                                                             • Patients presenting with acute colonic obstruction if successfully

                                                                 FOxTROT was developed by the NCRI Colorectal Cancer Clinical Study Group and is funded by Cancer Research UK

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