NCT00537823 — Pre- and Post-operative FOLFOX Based Therapy for Patients With Colorectal Cancer With Liver Involvement · CancerIndex
Clinical trial · Interventional
Pre- and Post-operative FOLFOX Based Therapy for Patients With Colorectal Cancer With Liver Involvement
Effect of Short-duration Preoperative Neoadjuvant Therapy With FOLFOX Based Therapy on Morbidity After Liver Resection for Colorectal Cancer Metastases
The purpose of this study is to determine the effect of short-duration pre-operative FOLFOX based therapy on postoperative problems after liver surgery for patients with metastatic colorectal cancer.
Conditions
Conditions (2)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
Neoadjuvant therapy
Week 1
* Leucovorin 400 mg/m\^2 IV
* Oxaliplatin 85 mg/m\^2 IV Cetuximab 400 mg/m2 IV
* 5FU bolus 400 mg/m\^2
* 5FU CIVI 1200 mg/m\^2/day over 46 hours
Weeks 2, 4, 6, 8 \*Cetuximab 250 mg/m\^2 IV weekly
Weeks 3, 5, 7
* Leucovorin 400 mg/m\^2 IV
* Oxaliplatin 85 mg/m\^2 IV Cetuximab 400 mg/m\^2 IV
* 5FU bolus 400 mg/m\^2
* 5FU CIVI 1200 mg/m\^2/day over 46 hours
Wait 3-8 weeks after completion of therapy
Liver resection
Wait 4 weeks or until clinical status allows
Adjuvant Therapy
Week 1, 3, 5, 7, 9, 11, 13, 15
* Leucovorin 400 mg/m\^2 IV
* Oxaliplatin 85 mg/m\^2 IV Cetuximab 400 mg/m\^2 IV
* 5FU bolus 400 mg/m\^2
* 5FU CIVI 1200 mg/m\^2/day over 46 hours
Weeks 2, 4, 6, 8, 10, 12, 16
\*Cetuximab 250 mg/m\^2 IV weekly
interventionNames
Drug: Cetuximab
Drug: Leucovorin
Drug: Oxaliplatin
Drug: Fluorouracil
type
EXPERIMENTAL
label
Arm 2 K-Ras 12/13 codon mutation
description
Neoadjuvant Therapy
Weeks 1, 3, 5
* Leucovorin 400 mg/m\^2 IV
* Oxaliplatin 85 mg/m\^2 IV
* Bevacizumab 5 mg/kg IV
* 5FU bolus 400 mg/m\^2
* 5FU CIVI 1200 mg/m\^2
Week 7
* Leucovorin 400 mg/m\^2 IV
* Oxaliplatin 85 mg/m\^2 IV
* 5FU bolus 400 mg/m\^2
* 5FU CIVI 1200 mg/m\^2
Wait 3-8 weeks after completion of therapy
Liver resection
Wait 4 weeks or until clinical status allows
Adjuvant Therapy
Weeks 1, 3, 5, 9, 11, 13
* Leucovorin 400 mg/m\^2 IV
* Oxaliplatin 85 mg/m\^2 IV
* Bevacizumab 5 mg/kg IV
* 5FU bolus 400 mg/m\^2
* 5FU CIVI 1200 mg/m\^2
Week 7, 15
* Leucovorin 400 mg/m\^2 IV
* Oxaliplatin 85 mg/m\^2 IV
* 5FU bolus 400 mg/m\^2
* 5FU CIVI 1200 mg/m\^2
Eligibility
Eligibility (as posted)
Sex
All
Minimum age
18 Years
Show eligibility criteria text
Inclusion Criteria:
* Synchronous or metachronous colorectal metastases
* Technically resectable liver metastases
* Four or fewer metastases
* No tumors in porta hepatis
* Resection of no more than 70% of liver needed
* Medically suitable candidate for major liver resection
* FDG-PET scan without metastatic disease outside the liver
Exclusion Criteria:
* Near-obstructing or obstructing colon lesions in patients in whom combined resection is planned (as delay for preoperative chemotherapy would be medially impossible)
* Treatment with FOLFOX or cetuximab within 12 months
* Treatment with irinotecan within 12 months
* Abnormal liver function (ALT or AST \> 5x ULN, bilirubin \> 3x ULN)
* Body mass index \>/= 35 kg/m² (as the risk for steatohepatitis is increased)
* Renal insufficiency (Cr \> 2.5mg/dL)
* Interstitial lung disease (because cetuximab has been rarely associated with development of interstitial lung disease)
* ECOG performance score \>/= 3
* Patients unable to give informed consent
* Pregnant patient (as cetuximab is a Class C drug)
* Peripheral neuropathy \>/= grade II (as oxaliplatin causes neuropathy to worsen)
References
Publications (42)
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interventionNames
Drug: Bevacizumab
Drug: Leucovorin
Drug: Oxaliplatin
Drug: Fluorouracil
Primary outcomes (3)
measure
Postoperative Complication Rate
timeFrame
30 days following surgery
description
Fraction of patients with any grade of complication I-V
measure
Major Postoperative Complication Rate
timeFrame
30 days following surgery
description
Fraction of patients with any complication grades IV and V
measure
All-cause Mortality
timeFrame
30 days following surgery
Secondary outcomes (6)
measure
Postoperative Recurrence Patterns
timeFrame
Up to 5 years
description
Liver only vs distant disease
measure
Histologic Hepatic Toxicity at Surgery
timeFrame
Time of surgery (approximately 11-16 weeks)
measure
Nonalcoholic Steatohepatitis Score (0-3)
timeFrame
Time of surgery (approximately 11-16 weeks)
description
* NASH Scoring
* Steatosis \*\*\<5% = 0
\*\*5-33%=1
\*\*\>33-66%=2
\*\*\>66%=3
* Lobular inflammation
\*\*No foci=0
\*\*\<2 foci per x 200 field=1
\*\*2-4 foci per x 200 field=2
\*\*\>4 foci per x 200 field=3
* Hepatocellular ballooning \*\*None=0 \*\*Few balloon cells = 1 \*\*Many cells/prominent ballooning=2
measure
Liver Injury Scale Score (0-27)
timeFrame
Time of surgery (approximately 11-16 weeks)
measure
Effect of Preoperative Chemotherapy on Tumor Size
timeFrame
Upon completion of neoadjuvant chemotherapy (approximately 2 months)
description
Number of participants whose tumor size decreased from baseline to completion of preoperative chemotherapy.
measure
Change in Tumor Size From Pretreatment to Preoperative CT Scan
timeFrame
Completion of neoadjuvant therapy (approximately 8 weeks)
description
-Compare total longest diameter from baseline to preoperative CT scan.
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