FOLFOX Plus SIR-SPHERES MICROSPHERES Versus FOLFOX Alone in Patients With Liver Mets From Primary Colorectal Cancer (SIRFLOX)

• ClinicalTrials.gov Identifier: NCT00724503
• Recruitment Status: Completed
• First Posted: July 29, 2008
• Results First Posted: March 26, 2019
• Last Update Posted: March 26, 2019
• Sponsor: Sirtex Medical
• Information provided by (Responsible Party): Sirtex Medical

Tracking Information

• First Submitted Date: July 25, 2008
• First Posted Date: July 29, 2008
• Results First Submitted Date: November 7, 2018
• Results First Posted Date: March 26, 2019
• Last Update Posted Date: March 26, 2019
• Actual Study Start Date: August 2006
• Actual Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 1, 2019)

Progression-Free Survival (PFS) at Any Site [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months ]

PFS defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as an increase in the sum of the longest diameters of ≥ 20% and an absolute increase in the sum of the longest diameters of ≥ 5 mm, or the appearance of a new lesion.

• Original Primary Outcome Measures (submitted: July 28, 2008): progression free survival [ Time Frame: from randomisation until progressive disease is confirmed or upon patient death if disease progression has not been evident at that time ]

Current Secondary Outcome Measures (submitted: March 1, 2019)

Percentage of Participants With Overall Response [ Time Frame: Through study completion, up to 60 months ]

Tumour Response Rate per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT: Complete Response (CR) - Disappearance of all target lesions which is confirmed if determined by two observations not less than 4 weeks apart; Partial Response (PR) - >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: FOLFOX Plus SIR-SPHERES MICROSPHERES Versus FOLFOX Alone in Patients With Liver Mets From Primary Colorectal Cancer
• Official Title: Randomised Comparative Study Of Folfox6m Plus Sir-Spheres® Microspheres Versus Folfox6m Alone As First Line Treatment In Patients With Nonresectable Liver Metastases From Primary Colorectal Carcinoma

Brief Summary

This study is a randomized multi-center trial that will assess the effect of adding Selective Internal Radiation Therapy (SIRT), using SIR-Spheres microspheres®, to a standard chemotherapy regimen of FOLFOX as first line therapy in patients with non-resectable liver metastases from primary colorectal adenocarcinoma.

Treatment with the biologic agent bevacizumab, if part of the standard of care at participating institutions, is allowed within this study at the discretion of the treating Investigator.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Colorectal Cancer
• Colorectal Carcinoma
• Liver Metastases

Intervention

• Device: SIR-Spheres yttrium-90 microspheres

  SIR-Spheres microspheres (yttrium-90 [Y-90] labelled resin microspheres), hepatic artery injection administered on Day 3 or 4 of cycle 1.

  mFOLFOX6 administered on Day 1 and at the start of each cycle every 14 days: 85 or 60 mg/m2 oxaliplatin by 2-hour intravenous (IV) infusion + 200 mg/m2 leucovorin by 2-hour IV infusion + 400 mg/m2 5-fluorouracil (5-FU) by IV bolus + 2.4 g/m2 5-FU by 46-hour continuous IV infusion.

  Treatment with the biologic agent bevacizumab, if part of standard practice at the participating institution, was permitted at the discretion of the treating Investigator.

  In the event that leucovorin was not available, use of levofolinic acid (the active S enantiomer) was acceptable at half the dose of the racemic leucovorin i.e. 100 mg/m2.

  Other Names:

  • mFOLFOX6m + SIRT
  • SIR-Spheres Y-90 microspheres
• Drug: Systemic chemotherapy (FOLFOX)

  mFOLFOX6 administered on Day 1 and at the start of each cycle every 14 days: 85 or 60 mg/m2 oxaliplatin by 2-hour intravenous (IV) infusion + 200 mg/m2 leucovorin by 2-hour IV infusion + 400 mg/m2 5-fluorouracil (5-FU) by IV bolus + 2.4 g/m2 5-FU by 46-hour continuous IV infusion.

  Treatment with the biologic agent bevacizumab, if part of standard practice at the participating institution, was permitted at the discretion of the treating Investigator.

  In the event that leucovorin was not available, use of levofolinic acid (the active S enantiomer) was acceptable at half the dose of the racemic leucovorin i.e. 100 mg/m2.

  Other Name: mFOLFOX6

Study Arms

• Experimental: mFOLFOX6 + SIRT
  A single injection of SIR-Spheres microspheres into the liver plus systemic chemotherapy consisting of Oxaliplatin + Leucovorin + 5-Fluorouracil (FOLFOX)
  Intervention: Device: SIR-Spheres yttrium-90 microspheres
• Active Comparator: mFOLFOX6
  Systemic chemotherapy consisting of Oxaliplatin + Leucovorin + 5- Fluorouracil (FOLFOX).
  Intervention: Drug: Systemic chemotherapy (FOLFOX)

Publications *

• van Hazel GA, Heinemann V, Sharma NK, Findlay MP, Ricke J, Peeters M, Perez D, Robinson BA, Strickland AH, Ferguson T, Rodriguez J, Kroning H, Wolf I, Ganju V, Walpole E, Boucher E, Tichler T, Shacham-Shmueli E, Powell A, Eliadis P, Isaacs R, Price D, Moeslein F, Taieb J, Bower G, Gebski V, Van Buskirk M, Cade DN, Thurston K, Gibbs P. SIRFLOX: Randomized Phase III Trial Comparing First-Line mFOLFOX6 (Plus or Minus Bevacizumab) Versus mFOLFOX6 (Plus or Minus Bevacizumab) Plus Selective Internal Radiation Therapy in Patients With Metastatic Colorectal Cancer. J Clin Oncol. 2016 May 20;34(15):1723-31. doi: 10.1200/JCO.2015.66.1181. Epub 2016 Feb 22. Erratum In: J Clin Oncol. 2016 Nov 20;34(33):4059.
• Wolstenholme J, Fusco F, Gray AM, Moschandreas J, Virdee PS, Love S, Van Hazel G, Gibbs P, Wasan HS, Sharma RA. Quality of life in the FOXFIRE, SIRFLOX and FOXFIRE-global randomised trials of selective internal radiotherapy for metastatic colorectal cancer. Int J Cancer. 2020 Aug 15;147(4):1078-1085. doi: 10.1002/ijc.32828. Epub 2020 Jan 9.
• Wasan HS, Gibbs P, Sharma NK, Taieb J, Heinemann V, Ricke J, Peeters M, Findlay M, Weaver A, Mills J, Wilson C, Adams R, Francis A, Moschandreas J, Virdee PS, Dutton P, Love S, Gebski V, Gray A; FOXFIRE trial investigators; SIRFLOX trial investigators; FOXFIRE-Global trial investigators; van Hazel G, Sharma RA. First-line selective internal radiotherapy plus chemotherapy versus chemotherapy alone in patients with liver metastases from colorectal cancer (FOXFIRE, SIRFLOX, and FOXFIRE-Global): a combined analysis of three multicentre, randomised, phase 3 trials. Lancet Oncol. 2017 Sep;18(9):1159-1171. doi: 10.1016/S1470-2045(17)30457-6. Epub 2017 Aug 3.
• Virdee PS, Moschandreas J, Gebski V, Love SB, Francis EA, Wasan HS, van Hazel G, Gibbs P, Sharma RA. Protocol for Combined Analysis of FOXFIRE, SIRFLOX, and FOXFIRE-Global Randomized Phase III Trials of Chemotherapy +/- Selective Internal Radiation Therapy as First-Line Treatment for Patients With Metastatic Colorectal Cancer. JMIR Res Protoc. 2017 Mar 28;6(3):e43. doi: 10.2196/resprot.7201.
• Gibbs P, Gebski V, Van Buskirk M, Thurston K, Cade DN, Van Hazel GA; SIRFLOX Study Group. Selective Internal Radiation Therapy (SIRT) with yttrium-90 resin microspheres plus standard systemic chemotherapy regimen of FOLFOX versus FOLFOX alone as first-line treatment of non-resectable liver metastases from colorectal cancer: the SIRFLOX study. BMC Cancer. 2014 Dec 1;14:897. doi: 10.1186/1471-2407-14-897.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 1, 2019): 530
• Original Estimated Enrollment (submitted: July 28, 2008): 318
• Actual Study Completion Date: May 2015
• Actual Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Unequivocal and measurable CT evidence of liver metastases which are not treatable by surgical resection or local ablation.
• Limited extra-hepatic metastases in the lung and/or lymph nodes are permitted (Lung: 5 lesions total, < 1 cm, or 1 single lesion of up to 1.7 cm; Lymph nodules in one single anatomic area (pelvis, abdomen or chest): any number, < 2 cm).
• Suitable for either treatment regimen.
• Prior chemotherapy for metastatic colorectal cancer is not allowed.
• WHO performance status 0-1.
• Adequate hematological, renal and hepatic function.
• Age 18 years or older.
• Willing and able to provide written informed consent.
• Life expectancy of at least 3 months without any active treatment.

Exclusion Criteria

• Evidence of ascites, cirrhosis, portal hypertension, main portal or venous tumor involvement or thrombosis as determined by clinical or radiologic assessment.
• Previous radiotherapy delivered to the upper abdomen.
• Non-malignant disease that would render the patient unsuitable for treatment according to the protocol.
• Peripheral neuropathy > grade 1 (NCI-CTC).
• Dose limiting toxicity with previous adjuvant 5-FU or oxaliplatin chemotherapy.
• Prior non-adjuvant chemotherapy for any malignancy. Adjuvant chemotherapy for colorectal cancer is not an exclusion criteria provided that it was completed more than 6 months before entry into the study.
• Pregnant or breast-feeding.
• Other active malignancy.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Belgium, France, Germany, Israel, Italy, New Zealand, Poland, Spain, Switzerland, United States

Administrative Information

• NCT Number: NCT00724503
• Other Study ID Numbers: STX0206
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Sirtex Medical
• Original Responsible Party: David Cade, MD, Medical Director, Sirtex Technology Pty Ltd
• Current Study Sponsor: Sirtex Medical
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Peter Gibbs, MD; Melbourne Health
• Principal Investigator: Guy van Hazel, MD; Mount Medical Centre

• PRS Account: Sirtex Medical
• Verification Date: March 2019