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A single injection of SIR-Spheres microspheres into the liver plus systemic chemotherapy consisting of Oxaliplatin + Leucovorin + 5-Fluorouracil (FOLFOX)

Systemic chemotherapy consisting of Oxaliplatin + Leucovorin + 5- Fluorouracil (FOLFOX).

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.

SIR-Spheres yttrium-90 microspheres

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.

Systemic chemotherapy (FOLFOX)

Peter Gibbs, MD

Guy van Hazel, MD

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.

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

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

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.

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.

Sirtex Medical

Adverse Events monitored for all participants who were randomized and received at least 1 cycle of study treatment.

Of the 267 in 'mFOLFOX6 Plus SIRT' arm, 18 switched study treatment arms and 3 did not get any treatment. Hence safety population in this arm comprises 246 participants.

The 'mFOLFOX6 alone' arm includes the initial 263 plus 18 that switched over. 11 did not receive any treatment. Hence safety population in this arm comprises 270 participants.

mFOLFOX6 Plus SIRT

systemic chemotherapy consisting of Oxaliplatin + Leucovorin + 5-Fluorouracil (FOLFOX)

mFOLFOX6 Alone

Systemic chemotherapy consisting of Oxaliplatin + Leucovorin + 5-Fluorouracil (FOLFOX)

Total

Age was unknown for 1 patient as patient withdrew consent and records

Age, Continuous

Sex was unknown for 1 patient as patient withdrew consent and records

Sex: Female, Male

Race (NIH/OMB)

Unknown

WHO performance status: (0) Able to carry out all normal activity without restriction

(1) Restricted in physically strenuous activity but ambulatory and able to carry out light work

WHO performance status

Primary tumor in situ

Extra-hepatic metastases at randomization

Tumor liver involvement %

Synchronous metastases

Janet Bell, M.B.A.

The null hypothesis tested for the primary efficacy endpoint is rate of progression (months) of SIRT/FOLFOX treatment versus FOLFOX is equal for both groups. The two-sided alternative hypothesis tested with 95% confidence is PFS rate for SIRT/FOLFOX treatment lower to that of FOLFOX.

Progression-Free Survival (PFS) at Any Site

A sample size of at least 450 patients for the SIRFLOX study was estimated to be needed to detect an increase in the median PFS at any site from 9.4 months to 12.5 months with 80% power and 95% confidence. Taking into account the number of patients who might receive the alternative treatment or lack of imaging data, the sample size was increased to 530. The Null hypothesis is no difference between the treatment arms with respect to PFS.

A single injection of SIR-Spheres microspheres into the liver plus systemic chemotherapy consisting of Oxaliplatin + Leucovorin + 5-Fluorouracil (FOLFOX)

SIR-Spheres yttrium-90 microspheres: SIR-Spheres microspheres implanted once on the 3rd or 4th day of the first week of the first chemotherapy cycle

Systemic chemotherapy (FOLFOX): Oxaliplatin 60 mg/m2,IV infusion, q two weeks for first 3 cycles

Oxaliplatin 85 mg/m2, IV infusion, q two weeks from cycle 4 onwards

Leucovorin 200 mg/m2, IV infusion, q two weeks

5-Fluorouracil 400 mg/m2, IV bolus, q two weeks

5-Fluorouracil 2.4 g/m2, IV infusion, q two weeks

B: FOLFOX + SIR-Spheres

Systemic chemotherapy consisting of Oxaliplatin + Leucovorin + 5- Fluorouracil (FOLFOX)

Systemic chemotherapy (FOLFOX): Oxaliplatin 85 mg/m2, IV infusion, q two weeks

Leucovorin 200 mg/m2, IV infusion, q two weeks

5-Fluorouracil 400 mg/m2, IV bolus, q two weeks

5-Fluorouracil 2.4 g/m2, IV infusion, q two weeks

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
FOLFOX Plus SIR-SPHERES MICROSPHERES Versus FOLFOX Alone in Patients With Liver Mets From Primary Colorectal Cancer	NCT00724503	Colorectal Canc... Colorectal Carc... Liver Metastase...	SIR-Spheres ytt... Systemic chemot...	18 Years -	Sirtex Medical
FOLFOX Plus SIR-SPHERES MICROSPHERES Versus FOLFOX Alone in Patients With Liver Mets From Primary Colorectal Cancer	NCT00724503	Colorectal Canc... Colorectal Carc... Liver Metastase...	SIR-Spheres ytt... Systemic chemot...	18 Years -	Sirtex Medical

Spots Global Cancer Trial Database for systemic chemotherapy (folfox)