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Role of Deficient DNA Mismatch Repair Status In Coordinating Center, NCCTG: N0147 CTSU: N0147 CALGB: N0147 ECOG: N0147 NCIC CTG: CRC.2 SWOG: N0147 North Central Cancer Treatment Group A Randomized Phase III Trial of Oxaliplatin (OXAL) Plus 5-Fluorouracil (5-FU)/Leucovorin (CF) with or without Cetuximab (C225) after Curative Resection for Patients with Stage III Colon Cancer Intergroup Study Chairs Steven R. Alberts, M.D. (Research Base)* Mayo Foundation 200 First Street, SW Rochester, MN 55905 Phone: (507) 284-1328 Fax: (507) 284-5280 E-mail: [email protected] Statisticians Daniel J. Sargent, Ph.D. Mayo Foundation 200 First Street SW Rochester, MN 55905 E-mail: [email protected] Michelle R. Mahoney, M.S. Fax: (507) 266-2477 Phone: (507) 284-8803 * Investigator having NCI responsibility for this protocol. DCTD Supplied Agent via Clinical Supplies Agreement (CSA): Cetuximab (NSC #714692) (Discontinued as of November 25, 2009) Commercial Supplied for patients pre-randomized following the implementation of Addendum 10: Oxaliplatin Document History (Effective Date) Document History (Effective Date) Activation February 10, 2004 NCCTG Addendum 7 January 4, 2008 NCCTG Update 1 February 10, 2004 NCCTG Addendum 8 May 12, 2008 NCCTG Addendum 1 March 29, 2004 NCCTG Addendum 9 August 18, 2008 NCCTG Addendum 2 September 1, 2004 NCCTG Update 3 August 18, 2008 NCCTG Addendum 3 June 1, 2005 NCCTG Addendum 10 May 8, 2009 NCCTG Addendum 4 June 1, 2005 NCCTG Addendum 11 December 18, 2009 NCCTG Addendum 5 August 1, 2005 NCCTG Addendum 12 September 22, 2010 NCCTG Addendum 6 August 15, 2007 NCCTG Addendum 13 June 1, 2011 NCCTG Update 2 August 15, 2007 NCI Version date: April 21, 2011 N0147 2 Addendum 13 Add As of November 25, 2009, all patient enrollments are complete. 3,6,7,9,10,11,1 2,13 Study Co-Chairs NCCTG Suresh G. Nair, M.D. ECOG Emily Chan, M.D. CALGB Richard M. Goldberg, M.D. NCIC CTG Sharlene Gill, M.D. NSABP Morton Kahlenberg, M.D. SWOG Anthony F. Shields, M.D., Ph.D. Laboratory Co-Chair Frank A. Sinicrope, M.D. Mayo Foundation 200 First Street SW Rochester, MN 55905 Phone: (507) 284-4511 Fax: (507) 284-5486 E-mail: [email protected] Thomas C. Smyrk, M.D. (Pathology - Mayo)9 James T. Quesenberry, M.D. (Pathology – NCCTG)9 Thomas A. Webb, M.D. (Pathology – NCCTG)9 Gist Farr, M.D. (Pathology – NCCTG)9 Paul Mazzara, M.D. (Pathology – NCCTG)9 Stephen N. Thibodeau, Ph.D (Laboratory – Research Base)9 9 Study contributor not responsible for patient care. N0147 3 Addendum 13 Protocol Resources (Contact Information) Questions: NCCTG Contact: Add 13 The study protocol and all related forms and documents must be downloaded from the N0147 web page of the CTSU Member web site located at https://www.ctsu.org. Sites must use the current form version and adhere to the instructions and submission schedule outlined in the protocol. CTSU sites should follow procedures outlined in the protocol for Adverse Event Reporting and Data Submission. Submit study data directly to NCCTG NCCTG will manage all data collection processes for this study. Effective June 1, 2011, all NCCTG sites (until August 31, 2011) and all non-NCCTG sites all data and forms are to be mailed directly to: NCCTG Operations Office Attention: Quality Assurance Office (Study N0147) RO FF 03 24-CC/NW Clinic 200 First Street SW Rochester MN 55905 Beginning September 1, 2011, all NCCTG sites will submit all forms via the NCCTG Remote Data Entry System. Do not copy CTSU on any study data or forms submissions. Add Protocol Document, Regulatory Issues NCCTG Research Base Research Protocol Specialists: 3,5,6,8, Angela C. Patterson-LaBaw 10,13 Phone: (507) 538-7339 Fax: (507) 284-5280 E-mail: [email protected] Patricia A. Aggen Phone: (507) 538-6232 Fax: (507) 284-5280 E-mail: [email protected] Add Paraffin-embedded Tissue Pathology NCCTG Research Base Pathology Coordinators: 4,6,7,9, Jennifer Mentlick 11,13 Phone: (507) 293-3928 Fax: (507) 284-1902 E-mail: [email protected] Christine R. Maszk Phone: (507) 266-8919 Fax: (507) 284-1902 E-mail: [email protected] Non-paraffin Biospecimens Roxann Neumann, RN, BSN, CCRP NCCTG Research Base Biospecimen Resource Manager Add Phone: (507) 538-0602 6,9,11 Fax: (507) 266-0824 Email: [email protected] Patient Eligibility or Treatment-Related Questions Lisa Finstuen NCCTG Quality Assurance Specialist Add 2,3,4,5,6,1 Phone: (507) 284-1328 0,13 Fax: (507) 284-1902 E-mail: [email protected] Add Adverse Events Patricia McNamara 10 NCCTG Research Base AdEERS Coordinator Phone: 507/266-3028 Fax: 507/284-9628 E-mail: [email protected] N0147 4 Addendum 13 Protocol Advisors Translational Research Component Investigator: Epidemiology: Frank A. Sinicrope, M.D. Paul J. Limburg, M.D. Mayo Foundation Mayo Foundation 200 First Street SW 200 First Street SW Rochester, MN 55901 Rochester, MN 55901 Phone: (507) 284-8432 Phone: (507) 266-4338 Fax: (507) 284-1803 Fax: (507) 266-0350 E-mail: [email protected] E-mail: [email protected] N0147 5 Addendum 13 Index Schema 1.0 Background 2.0 Goals 3.0 Patient Eligibility 4.0 Test Schedule Add 3,11 5.0 Stratification Factors at the Time of Registration/Randomization Add 9 6.0 Registration/Randomization Procedures (all cooperative groups; also see Appendix XII) 7.0 Protocol Treatment 8.0 Dosage Modification Based on Adverse Events 9.0 Ancillary Treatment 10.0 Adverse Event (AE) Reporting and Monitoring Add 6 11.0 Treatment Evaluation Add 5,9 12.0 Descriptive Factors at the Time of Registration/Randomization 13.0 Treatment/Follow-up Decision at Evaluation of Patient 14.0 Translational/Pharmacologic Studies 15.0 Drug Information 16.0 Statistical Considerations and Methodology 17.0 Pathology Considerations for Quality Control 18.0 Records and Data Collection Procedures 19.0 Budget 20.0 References Add 5,6 Appendix I: Consent Form Appendix II: ECOG Performance Status Appendix III: New York Heart Association Classifications Appendix IV: Patient Instructions for Preventing and Treating Diarrhea Appendix V: Administering Questionnaires: Instructions for Clinical Research Associates (CRAs) – Add 9 Questionnaires are no longer required for patients enrolled following implementation of Addendum 9. Add 7 Appendix VI: Linear Analogue Self Assessment (LASA) Scale - As of Addendum 7, the LASA is no longer required for newly enrolled patients. Appendix VII: Brief Food Questionnaire– Questionnaires are no longer required for patients enrolled following Add 9 implementation of Addendum 9. Appendix VIII: Completion Questions– Questionnaires are no longer required for patients enrolled following Add 9 implementation of Addendum 9. Add 1,6,9 Appendix IX: Focused Health Assessment (Patient Questionnaire) – Questionnaires are no longer required for patients enrolled following implementation of Addendum 9. Add 11 Appendix X: Patient and Physician Fact Sheet – No longer used as of Addendum 11. Appendix XI: NCI/Sanofi-Aventis CRADA Add 13 Appendix XII: Additional N0147 Information Appendix XIII: Blood Specimen Logistics Appendix XIV: Translational Research (also see Sections 14.0 and 17.0) Add 2 Appendix XV: Request Letter for Immunohistochemistry (IHC) Test Results Add 5 Appendix XVI: Dear Participant Letter Add 9,10 Appendix XVII Instrumentation Guide for the DxS KRAS Kits – For use at NCCTG Research Base Only Add 10 Appendix XVIII Quick Reference Guide for Submitting Pathology Materials N0147 6 Addendum 13 Schema Add 9,12 Closed to enrollment, effective November 25, 2009. Arm A – (FOLFOX) Oxaliplatin + 5- fluorouracil/Leucovorin Regimen Oxaliplatin IV over 2 hours x Leucovorin IV over 2 hours x 5-FU IV push Observation Event x 5-FU continuous infusion over 46 hours every 6 months P Monitoring – If Wild Type Repeat for 12 cycles until 5 years Recurrence r until 8 years KRAS following e Randomization randomization from random- - ization R ARM D: FOLFOX + Cetuximab x Oxaliplatin IV over 2 hours a n x Leucovorin IV over 2 hours x 5-FU IV push d x 5-FU continuous infusion over 46 hours o x Cetuximab IV over 2 hours (loading dose) m then weekly IV i z Repeat for 12 cycles a t i If Mutated ARM G: Locally-Directed Therapy o KRAS or Registration x Report summary of therapy n KRAS Not x Annual status reports until 8 years from Evaluable registration Generic name: Oxaliplatin Cetuximab Fluorouracil, Calcium leucovorin, 5-fluorouracil Calcium folinate, Add 2 Citrovorum factor, Folinic acid Brand name: Eloxatin Erbitux Adrucil Leucovorin Mayo abbreviation: OXAL C225 5-FU CF *Blood draws for Section 14.2 must be collected following pre-randomization, prior to registration/randomization (all patients) Add 6,12 and at the time of the first Observation visit, or the next Observation visit for patients already in the Observation phase (Arm A or Arm D patients only). Site must provide NCCTG patient ID that is given at pre-randomization, with the submitted blood samples and on all applicable forms. N0147 7 Addendum 13 1.0 Background 1.1 Disease Incidence and Prognosis 1.11 Colorectal cancers are among the most common malignant tumors in North Americans. 147,300 new cases and 48,100 deaths are anticipated in the United States alone from this disease in 2002 (1). Most patients present with tumors that appear limited to the locoregional area. Those patients undergo resection with curative intent (2-4). Many previous studies have demonstrated that individuals with stage I and early stage II tumors (Modified Astler-Coller A and B1 [T1-2NoMo]) have a >90% 5-year survival. Chemotherapy postoperatively is unnecessary for this favorable prognostic group. However, 40-60% of all patients who undergo resection for potential cure have more advanced locoregional disease.
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