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Prospective Randomized Trial Evaluating Mandatory Second Look Surgery With HIPEC and CRS vs. Standard of Care in Subjects at High Risk of Developing Colorectal Peritoneal Metastases

Phase 2
18 Years
70 Years
Not Enrolling
Colorectal Carcinoma, Peritoneal Carcinomatosis

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Trial Information

Prospective Randomized Trial Evaluating Mandatory Second Look Surgery With HIPEC and CRS vs. Standard of Care in Subjects at High Risk of Developing Colorectal Peritoneal Metastases


- Peritoneal carcinomatosis (PC) from colorectal cancer (CRC) treated with chemotherapy
alone results in median survival of 5 to 13 months.

.-Approximately, 55% of high risk patients (Patients presenting with synchronous PC,
ovarian metastases perforated primary, and emergency presentation with bleeding or
obstructing lesions) will develop PC.

- Early PC is undetectable by conventional imaging.

- Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for
early PC from CRC resulted in median survival of 48-63 months and 5 year survival of 51

- This study is a prospective randomized trial designed to answer the question whether
mandatory second look surgery (MSLS) with CRS and HIPEC will prolong overall survival
when compared to the standard of care.


Primary Objective:

- To compare the overall survival of patients at high risk for developing PC from CRC who
undergo M SLS + HIPEC and CRS (if applicable) vs. similar patients who receive standard of

Secondary Objectives:

- To determine recurrence-free survival in both arms.

- To investigate selection criteria for patient who might benefit from a strategy of MSLS
with CRS + HIPEC.


- Patients who have undergone curative resection f or CRC who are at high risk for

- Patients who shown no evidence of disease at the time of enrollment

- Patients with ECOG less than or equal to 0-2 and suitable candidates for laparotomy,


- High risk CRC patients for developing PC who underwent curative surgery and
subsequently received standard of care and remained NED for 12 months after primary
surgery will be randomized into MSLS/CRS/HIPEC or continuing standard of care.

- HIPEC will be done using Oxaliplatin/5-FU/Leucovorin.

- Up to 100 patients will be enrolled to allow for 35 evaluable patients in each arm;
accrual is expected to last 5 years.

Inclusion Criteria


1. Histologically confirmed colorectal adenocarcinoma.

2. Curative resection (NED at closure) for CRC which was (1) perforated into the
peritoneal cavity, (2) associated with minimal PC which was completely excised
at the time of initial operation, (3) T4 lesion that required en bloc resection
of additional organs, (4) associated with ovarian metastases or (5) emergency
presentation with lesions associated with obstruction and/or bleeding.

Note: Patient who presented at the time of diagnosis with limited extra
abdominal metastases may be eligible if the lesions were completely resected and
the patient remains NED.

3. Received at least 3 months of standard of care adjuvant therapy and is disease
free by conventional imaging at time of registration and/or randomization.

Note: The imaging will be reviewed by an experienced radiologist and a surgical
attending prior to enrollment.

4. Greater than or equal to 18 years of age.

5. Must be able to understand and sign the Informed Consent

6. Clinical performance status of ECOG less than or equal to 2.

7. Life expectancy of greater than three months.

8. Patients of both genders must be willing to practice birth control during and
for four months after receiving chemotherapy.

9. Hematology:

- Absolute neutrophil count greater than 1500/mm(3) without the support of Filgrastim.

- Platelet count greater than 75,000/mm(3).

- Hemoglobin greater than 8.0 g/dl.

j. Chemistry:

- Serum creatinine less than or equal to 1.5 mg/dl unless the measured creatinine
clearance is greater than 60mL/min/1.73m(2).

- Total bilirubin less than or equal to 2 mg/dl, except for patients with diagnosis of
Gilbert's disease or hepatic pedicle obstruction then total bilirubin must be less
than or equal to 5 mg/dl.

k. INR less than or equal to 1.8.

l. Stable serum CEA levels

m. No history of prior/other malignancies within the 2 years prior to enrollment with
the exception of basal cell carcinoma.


1. Women of child-bearing potential who are pregnant or breast feeding because of the
potentially dangerous effects of the chemotherapy on the fetus or infant.

2. Active systemic infections, coagulation disorders or other major medical illnesses
precluding major surgery.

3. Prior experimental therapy with novel agents

4. Prior HIPEC

5. History of brain metastases

6. Childs B or C cirrhosis or with evidence of severe portal hypertension by history,
endoscopy, or radiologic studies or with evidence of moderate to severe ascites.

7. Weight less than 40 kg.

8. History of congestive heart failure and/or an LVEF < 40%

Note: Patients at increased risk for coronary artery disease or cardiac dysfunction
(e.g., > 65yo, diabetes, history of hypertension, elevated LDL, first degree relative
with coronary artery disease) will undergo full cardiac evaluation and will not be
eligible if they demonstrate significant irreversible ischemia on stress thallium or
an ejection fraction < 40%. Patients may be eligible if cardiac status is treated and
improves to within eligibility criteria.

9. Significant COPD or other chronic pulmonary restrictive disease with PFT's indicating
an FEV1 less than 50% or a DLCO less than 40% predicted for age.

Note: Patients who have shortness of breath with minimal exertion or who are at risk
for pulmonary disease (e.g., chronic smokers) will undergo pulmonary function

10. Discretion of principle investigator.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To compare the overall survival of patients at high risk for developing peritoneal carcinomatosis from colorectal cancer who undergo mandatory second look surgery + HIPEC and CRS (if applicable) vs. similar patients who receive standard of care.

Outcome Time Frame:

Follow-up will occur every 3 months for two years, every six months for three ye

Safety Issue:



United States: Federal Government

Study ID:




Start Date:

January 2010

Completion Date:

February 2012

Related Keywords:

  • Colorectal Carcinoma
  • Peritoneal Carcinomatosis
  • Colon Cancer
  • Rectal Cancer
  • Peritoneal Perfusion
  • Metastatic Cancer
  • Recurrence
  • Colorectal Cancer
  • Carcinoma
  • Colorectal Neoplasms
  • Neoplasm Metastasis



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