FOLFOX6m Plus SIR-Spheres Microspheres vs FOLFOX6m Alone in Patients With Liver Mets From Primary Colorectal Cancer (FOXFIREGlobal)

• ClinicalTrials.gov Identifier: NCT01721954
• Recruitment Status: Completed
• First Posted: November 6, 2012
• Results First Posted: October 22, 2019
• Last Update Posted: November 5, 2019
• Sponsor: Sirtex Medical
• Information provided by (Responsible Party): Sirtex Medical

Tracking Information

• First Submitted Date: October 26, 2012
• First Posted Date: November 6, 2012
• Results First Submitted Date: August 12, 2019
• Results First Posted Date: October 22, 2019
• Last Update Posted Date: November 5, 2019
• Actual Study Start Date: May 1, 2013
• Actual Primary Completion Date: December 23, 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 23, 2019)

Overall Survival (OS) [ Time Frame: From date of randomization until the date of death from any cause assessed up 3 yrs 8 months ]

OS defined as the time interval between the date of randomization and the date of death from any cause.

• Original Primary Outcome Measures: Not Provided

Current Secondary Outcome Measures (submitted: October 23, 2019)

Progression-free Survival [ 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 3 years 8 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 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: FOLFOX6m Plus SIR-Spheres Microspheres vs FOLFOX6m Alone in Patients With Liver Mets From Primary Colorectal Cancer
• Official Title: Assessment of Overall Survival of FOLFOX6m Plus SIR-Spheres Microspheres Versus FOLFOX6m Alone as First-line Treatment in Patients With Non-resectable Liver Metastases From Primary Colorectal Carcinoma in a Randomised Clinical Study

Brief Summary

This study is a randomized, multi-center study that will compare the efficacy and safety of selective internal radiation therapy (SIRT) using SIR-Spheres microspheres plus a standard chemotherapy regimen of FOLFOX6m versus FOLFOX6m alone as first-line therapy in patients with non-resectable liver metastases from primary colorectal carcinoma.

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 Investigator.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Colorectal Cancer Metastatic

Intervention

• Drug: FOLFOX6m
• Device: SIR-Spheres microspheres

Study Arms

• Active Comparator: Control Arm
  Systemic chemotherapy with FOLFOX6m plus or minus bevacizumab repeated every two weeks until evidence of treatment failure.
  Intervention: Drug: FOLFOX6m
• Experimental: Experimental Arm
  Systemic chemotherapy with FOLFOX6m plus or minus bevacizumab plus SIR-Spheres microspheres.
  Interventions:

  • Drug: FOLFOX6m
  • Device: SIR-Spheres microspheres

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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 2, 2019): 209
• Original Enrollment: Not Provided
• Actual Study Completion Date: February 28, 2017
• Actual Primary Completion Date: December 23, 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Age 18 years or older
• Willing and able to provide written informed consent
• 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)
• All imaging evidence used as part of the screening process must be within 28 days
• Suitable for either treatment regimen
• WHO performance status 0-1
• Adequate hematological, renal and hepatic function
• Life expectancy of at least 3 months without any active treatment

Exclusion Criteria:

• Evidence of ascites, cirrhosis, portal hypertension, main portal or venous involvement or thrombosis as determined by clinical or radiologic assessment
• Previous radiotherapy delivered to the liver
• Non-malignant disease that would render the patient unsuitable for treatment according to the protocol
• Peripheral neuropathy > grade 2 (NCI-CTC)
• Dose-limiting toxicity associated with previous adjuvant 5-FU or oxaliplatin chemotherapy
• Prior non-adjuvant chemotherapy for any malignancy. Adjuvant chemotherapy for colorectal cancer is permitted provided that it was completed more than 6 months before entry into the study
• Pregnant or breast feeding
• Concurrent or prior history of cancer other than adequately treated non-melanoma skin cancer or carcinoma in situ of the cervix
• Allergy to contrast media that would preclude angiography of the hepatic arteries

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, Korea, Republic of, New Zealand, Portugal, Singapore, Spain, Taiwan, United States

Administrative Information

• NCT Number: NCT01721954
• Other Study ID Numbers: STX0112
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Sirtex Medical
• Original Responsible Party: [Redacted]
• Current Study Sponsor: Sirtex Medical
• Original Study Sponsor: [Redacted]
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Sirtex Medical
• Verification Date: October 2019