Clinical trial NCT00537823
Conditions: Colorectal Cancer Metastases
Keywords: Colorectal Cancer Metastasis Neoadjuvant Therapy
Sponsor: Washington University School of Medicine
Start date: 2007-06-01; Completion date: 2011-07-01
Enrollment: 9 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
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.

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: arm 1: 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 arm 2: 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
Interventions: intervention 1: Cetuximab intervention 2: Bevacizumab intervention 3: Leucovorin intervention 4: Oxaliplatin intervention 5: Fluorouracil
Intervention descriptions: intervention 1: None intervention 2: None intervention 3: None intervention 4: None intervention 5: None

Protocol documents: