Pre- and Post-operative FOLFOX Based Therapy for Patients... | NCT00537823

Pre- and Post-operative FOLFOX Based Therapy for Patients... | NCT00537823 | Trialant

Description Module

Detailed Description

Although early stage, localized colon and rectal cancers are associated with 5 year survival rates of nearly 90%, only a minority of patients present with localized disease. Unfortunately, at the time of their initial presentation, approximately 35% of patients with colon or rectal cancer have metastatic disease. Nearly two thirds of these patients with stage IV disease have evidence of extrahepatic spread and have a median overall survival rate of 8-10 months in the absence of further treatment. Even with the most intensive chemotherapeutic regimens, the median overall survival for these patients ranges from 12 months to 20 months. However, a small subset of patients with stage IV disease has isolated hepatic metastatic disease and can undergo resection. The patients with completely resected liver metastases enjoy a significantly higher overall five-year survival, which is as high as 58% in carefully selected patients. Ten-year overall survival has been reported in 22% of patients. Despite this improvement, the five-year disease-free survival for these patients is at best 35%, with hepatic recurrences occurring in 46%.

The fact that adjuvant chemotherapy improves the three-year survival rate for stage II disease and five-year survival rates for stage III disease implies that it can treat micrometastatic disease in some fraction of patients. Because micrometastatic disease is likely the cause of the high recurrence rate in patients who undergo liver resection, there is a clear biologic rationale for using postoperative adjuvant chemotherapy after liver resection. Although this strategy is a common practice in many centers, no convincing data that this improves survival have been reported. A large randomized phase III trial (EORTC 40983) examining this question is currently ongoing and effect on survival has not yet been reported. Given that systemic chemotherapy after liver resection remains of unproven benefit at the present time, many have wondered if preoperative treatment might have more promise in improving recurrence rates.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Arm 1 - Wildtype	Experimental	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	Drug: Cetuximab Drug: Leucovorin Drug: Oxaliplatin Drug: Fluorouracil
Arm 2 K-Ras 12/13 codon mutation	Experimental	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	Drug: Bevacizumab Drug: Leucovorin Drug: Oxaliplatin Drug: Fluorouracil

Name	Type	Description	Arm Group Labels	Other Names
Cetuximab	Drug		Arm 1 - Wildtype	Erbitux
Bevacizumab

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Postoperative Complication Rate	Fraction of patients with any grade of complication I-V	30 days following surgery
Major Postoperative Complication Rate	Fraction of patients with any complication grades IV and V	30 days following surgery
All-cause Mortality		30 days following surgery

Secondary Outcomes

Measure	Description	Time Frame
Postoperative Recurrence Patterns	Liver only vs distant disease	Up to 5 years
Histologic Hepatic Toxicity at Surgery		Time of surgery (approximately 11-16 weeks)

Contacts/Locations Module

Name	Affiliation	Role
David Linehan, M.D.	Washington University School of Medicine	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Washington University School of Medicine		St Louis	Missouri	63110	United States

References Module

Citations

PubMed Identifier	Type	Citation
	Background	Adam R, Aloia T, Figueras J, Capussotti L, Poston G, Mentha G, Selzner M, and the LiverMetSurvey Scientific Committee. LiverMetSurvey: Analysis of clinicopathologic factors associated with the efficacy of preoperative chemotherapy in 2,122 patients with colorectal liver metastases. Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings Part I. Vol 24, No. 18S (June 20 Supplement), 2006: 3521.
11352309	Background	Adam R, Avisar E, Ariche A, Giachetti S, Azoulay D, Castaing D, Kunstlinger F, Levi F, Bismuth F. Five-year survival following hepatic resection after neoadjuvant therapy for nonresectable colorectal. Ann Surg Oncol. 2001 May;8(4):347-53. doi: 10.1007/s10434-001-0347-3.
16230673

Label	URL
Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine	View source

Arm/Group Information

ID	Title	Description
FG000	Arm 1 - Wildtype	Neoadjuvant therapy Week 1 Leucovorin 400 mg/m2 IV Oxaliplatin 85 mg/m2 IV Cetuximab 400 mg/m2 IV 5FU bolus 400 mg/m2 5FU CIVI 1200 mg/m2/day over 46 hours Weeks 2, 4, 6, 8 Cetuximab 250 mg/m2 IV weekly Weeks 3, 5, 7 Leucovorin 400 mg/m2 IV Oxaliplatin 85 mg/m2 IV Cetuximab 400 mg/m2 IV 5FU bolus 400 mg/m2 5FU CIVI 1200 mg/m2/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/m2 IV Oxaliplatin 85 mg/m2 IV Cetuximab 400 mg/m2 IV 5FU bolus 400 mg/m2 5FU CIVI 1200 mg/m2/day over 46 hours Weeks 2, 4, 6, 8, 10, 12, 16 Cetuximab 250 mg/m2 IV weekly
FG001	Arm 2 K-Ras 12/13 Codon Mutation	Neoadjuvant Therapy Weeks 1, 3, 5 Leucovorin 400 mg/m2 IV Oxaliplatin 85 mg/m2 IV Bevacizumab 5 mg/kg IV 5FU bolus 400 mg/m2 5FU CIVI 1200 mg/m2 Week 7 Leucovorin 400 mg/m2 IV Oxaliplatin 85 mg/m2 IV 5FU bolus 400 mg/m2 5FU CIVI 1200 mg/m2 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/m2 IV Oxaliplatin 85 mg/m2 IV Bevacizumab 5 mg/kg IV 5FU bolus 400 mg/m2 5FU CIVI 1200 mg/m2 Week 7, 15 Leucovorin 400 mg/m2 IV Oxaliplatin 85 mg/m2 IV 5FU bolus 400 mg/m2 5FU CIVI 1200 mg/m2

Periods

Title

Milestones

Reasons Not Completed

Overall Study

Type	Comment	Milestone Data
STARTED		FG0007 subjects FG0012 subjects
COMPLETED		FG0005 subjects FG0012 subjects
NOT COMPLETED		FG0002 subjects FG0010 subjects

Type	Comment	Reasons
Adverse Event		FG0002 subjects FG0010 subjects

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Arm 1 - Wildtype	Neoadjuvant therapy Week 1 Leucovorin 400 mg/m2 IV Oxaliplatin 85 mg/m2 IV Cetuximab 400 mg/m2 IV 5FU bolus 400 mg/m2 5FU CIVI 1200 mg/m2/day over 46 hours Weeks 2, 4, 6, 8 Cetuximab 250 mg/m2 IV weekly Weeks 3, 5, 7 Leucovorin 400 mg/m2 IV Oxaliplatin 85 mg/m2 IV Cetuximab 400 mg/m2 IV 5FU bolus 400 mg/m2 5FU CIVI 1200 mg/m2/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/m2 IV Oxaliplatin 85 mg/m2 IV Cetuximab 400 mg/m2 IV 5FU bolus 400 mg/m2 5FU CIVI 1200 mg/m2/day over 46 hours Weeks 2, 4, 6, 8, 10, 12, 16 Cetuximab 250 mg/m2 IV weekly

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Median

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Postoperative Complication Rate

Fraction of patients with any grade of complication I-V

4 participants did not have surgery.

Posted

Number

percentage of participants

30 days following surgery

ID	Title	Description
OG000	Arm 1 - Wildtype	Neoadjuvant therapy Week 1 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 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

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Arm 1 - Wildtype	Neoadjuvant therapy Week 1 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 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

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Hyperbilirubinemia	Investigations	CTCAE (3.0)	Systematic Assessment

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Seasonal allergies	Immune system disorders	CTCAE (3.0)	Systematic Assessment

More Info Module

Certain Agreements

Title	Organization	Phone	Extension	Email
David Linehan, M.D.	Washington University School of Medicine			David_Linehan@URMC.Rochester.edu

Condition Browse Module

ID	Term
D015179	Colorectal Neoplasms
D009362	Neoplasm Metastasis

ID	Term
D007414	Intestinal Neoplasms
D005770	Gastrointestinal Neoplasms
D004067	Digestive System Neoplasms
D009371	Neoplasms by Site

Intervention Browse Module

ID	Term
D000068818	Cetuximab
D000068258	Bevacizumab
D002955	Leucovorin
D000077150	Oxaliplatin
D005472	Fluorouracil

ID	Term
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins

Primary

Major Postoperative Complication Rate

Fraction of patients with any complication grades IV and V

4 participants did not have surgery.

Posted

Number

percentage of participants

30 days following surgery

ID	Title	Description
OG000	Arm 1 - Wildtype	Neoadjuvant therapy Week 1 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 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
OG001	Arm 2 K-Ras 12/13 Codon Mutation	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

Units	Counts
Participants	OG0004 OG0011

Title

Denominators

Categories

Title	Measurements
	OG00025 OG0010

Primary

All-cause Mortality

4 participants did not have surgery.

Posted

Number

participants

30 days following surgery

ID	Title	Description
OG000	Arm 1 - Wildtype	Neoadjuvant therapy Week 1 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 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
OG001	Arm 2 K-Ras 12/13 Codon Mutation	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

Units	Counts
Participants	OG0004 OG0011

Title

Denominators

Categories

Title	Measurements
	OG0000 OG0010

Secondary

Postoperative Recurrence Patterns

Liver only vs distant disease

7 participants were not evaluable. 4 participants did not have surgery (3 in Arm 1, 1 in Arm 2). 1 participant had surgery but was not resectable (Arm 1) . 1 participant developed another primary cancer (Arm 1). 1 participant died before recurrence from hepatic failure (Arm 1).

Posted

Number

participants

Up to 5 years

ID	Title	Description
OG000	Arm 1 - Wildtype	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
OG001	Arm 2 K-Ras 12/13 Codon Mutation	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

Units	Counts
Participants	OG0001 OG0011

Title

Denominators

Categories

Liver only

Title	Measurements
	OG0000 OG0010

Distant disease

Title	Measurements
	OG000

Secondary

Histologic Hepatic Toxicity at Surgery

4 participants did not have surgery.

Posted

Number

participants

Time of surgery (approximately 11-16 weeks)

ID	Title	Description
OG000	Arm 1 - Wildtype	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
OG001	Arm 2 K-Ras 12/13 Codon Mutation	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

Units	Counts
Participants	OG0004 OG0011

Title

Denominators

Categories

Not reported on pathology report

Title	Measurements
	OG0001 OG0010

Mild

Title	Measurements
	OG000

Secondary

Nonalcoholic Steatohepatitis Score (0-3)

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

4 participants did not have surgery and are not included in this outcome measure.

The study pathologist left the university early prior to completion of study pathology for this study.

Posted

Number

participants

Time of surgery (approximately 11-16 weeks)

ID	Title	Description
OG000	Arm 1 - Wildtype	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
OG001	Arm 2 K-Ras 12/13 Codon Mutation	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

Units	Counts
Participants	OG0004 OG0011

Title

Denominators

Categories

Not reported on pathology report

Title	Measurements
	OG0003 OG0010

Aborted surgery

Title	Measurements
	OG000

Secondary

Liver Injury Scale Score (0-27)

Data was not collected for this outcome measure as the study pathologist left the institution early prior to study closure.

Posted

Time of surgery (approximately 11-16 weeks)

ID	Title	Description
OG000	Arm 1 - Wildtype	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
OG001	Arm 2 K-Ras 12/13 Codon Mutation	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

Units	Counts
Participants	OG0000 OG0010

Secondary

Effect of Preoperative Chemotherapy on Tumor Size

Number of participants whose tumor size decreased from baseline to completion of preoperative chemotherapy.

2 participants did not have the CT scan prior to surgery as both did not complete preoperative chemotherapy due to adverse skin reactions to cetuximab.

Posted

Number

participants

Upon completion of neoadjuvant chemotherapy (approximately 2 months)

ID	Title	Description
OG000	Arm 1 - Wildtype	Neoadjuvant therapy Week 1 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 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
OG001	Arm 2 K-Ras 12/13 Codon Mutation	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

Units	Counts
Participants	OG0005 OG0012

Title

Denominators

Categories

Title	Measurements
	OG0004 OG0012

Secondary

Change in Tumor Size From Pretreatment to Preoperative CT Scan

-Compare total longest diameter from baseline to preoperative CT scan.

2 participants did not have the CT scan prior to surgery as both did not complete preoperative chemotherapy due to adverse skin reactions to cetuximab.

Posted

Median

Full Range

percentage of change of longest diameter

Completion of neoadjuvant therapy (approximately 8 weeks)

ID	Title	Description
OG000	Arm 1 - Wildtype	Neoadjuvant therapy Week 1 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 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
OG001	Arm 2 K-Ras 12/13 Codon Mutation	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

Units	Counts
Participants	OG0005 OG0012

Title

Denominators

Categories

Title	Measurements
	OG000-23.8(-71.7 to -0.7) OG001-14.3(-28.0 to 2.1)