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A Randomized Phase I/III Study Of Systematic Chemotherapy With Or Without Hepatic Chemoembolization For Liver-Dominant Metastatic Adenocarcinoma Of The Colon And Rectum


Phase 3
18 Years
N/A
Not Enrolling
Both
Colorectal Cancer, Metastatic Cancer

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Trial Information

A Randomized Phase I/III Study Of Systematic Chemotherapy With Or Without Hepatic Chemoembolization For Liver-Dominant Metastatic Adenocarcinoma Of The Colon And Rectum


OBJECTIVES:

- Compare the survival of patients with liver-dominant metastatic colorectal
adenocarcinoma treated with irinotecan, fluorouracil, and leucovorin calcium with or
without hepatic chemoembolization.

- Compare response in the liver, time to hepatic tumor progression, and time to
extrahepatic tumor progression in patients treated with these regimens.

- Compare the possible treatment differences with respect to morbidity, toxic effects of
chemoembolization, toxic effects of chemotherapy, and death from cancer-related
complications in these patients.

OUTLINE: This is a phase I dose-escalation study followed by a phase III randomized,
multicenter study. (Phase I closed as of 10/14/02.)

- Phase I: Patients in phase I are sequentially enrolled to 1 of 3 treatment regimens.
(Phase I closed as of 10/14/02.)

- Regimen A: Patients receive irinotecan IV over 60-90 minutes, leucovorin calcium
IV, and fluorouracil IV over 10 minutes on days 1, 8, 15, and 22. Patients undergo
hepatic embolization with embolic suspension only on day 36.

- Regimen B: Patients receive chemotherapy as in regimen A. Patients undergo hepatic
chemoembolization with lower-dose cisplatin, doxorubicin, and mitomycin on day 36.

- Regimen C: Patients receive chemotherapy as in regimen A. Patients undergo hepatic
chemoembolization with higher-dose cisplatin, doxorubicin, and mitomycin on day
36.

After 1 week of rest, patients in all regimens receive a second 4-week course of systemic
chemotherapy.

Cohorts of 3-10 patients are sequentially enrolled until the maximum tolerated dose (MTD) of
chemotherapy and chemoembolization is determined. The MTD is defined as the dose preceding
that at which at least 4 of 10 patients experience dose-limiting toxicity.

- Phase III: Patients are stratified according to liver volume involvement (less than 25%
vs 25-50% vs more than 50% to less than 75%) and participating center. Patients are
randomized to 1 of 2 treatment arms.

- Arm I: Patients receive irinotecan IV over 60-90 minutes, leucovorin calcium IV,
and fluorouracil IV over 10 minutes on days 1, 8, 15, and 22. Courses repeat every
6 weeks in the absence of disease progression.

- Arm II: Patients receive chemotherapy as in arm I. Patients undergo hepatic
chemoembolization with cisplatin, doxorubicin, and mitomycin on day 36.
Chemotherapy repeats every 6 weeks in the absence of disease progression.
Chemoembolization may repeat every 6 weeks for 2-4 courses as necessary.

Patients in phase III are followed every 3 months for 2 years, every 6 months for 3 years,
and then annually thereafter.

PROJECTED ACCRUAL: A total of 9-18 patients will be accrued for phase I of this study.
(Phase I closed to accrual as of 10/14/02.) Approximately 315 patients will be accrued for
phase III of this study within 2.5 years.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically confirmed metastatic colorectal adenocarcinoma

- Measurable metastasis to liver at least 1.0 cm

- Less than 75% of total liver volume

- Known extrahepatic disease limited to lymph nodes and less than 2 cm

- No ascites

- Ineligible for surgery

PATIENT CHARACTERISTICS:

Age:

- 18 and over

Performance status:

- Zubrod 0-2

Life expectancy:

- Not specified

Hematopoietic:

- Absolute granulocyte count at least 2,000/mm^3

- Platelet count at least 90,000/mm^3

- No bleeding diathesis not correctable by standard therapy

Hepatic:

- Ineligible if all of the following criteria are concurrently present:

- High risk of hepatic failure (more than 50% liver involvement by tumor)

- Bilirubin greater than 2.0 mg/dL

- SGOT greater than 100 U/L

- Lactate dehydrogenase greater than 425 U/L

- No hepatic encephalopathy

- No portal vein occlusion without hepatopedal collateral flow demonstrated by
angiography

- No portal hypertension with hepatofugal flow

Renal:

- Creatinine no greater than 2.0 mg/dL

Cardiovascular:

- No myocardial infarction within the past 6 months

- No evidence of congestive heart failure

- No severe peripheral vascular disease that would preclude catheterization

Other:

- No severe allergy or intolerance to contrast media, narcotics, sedatives, or atropine

- No other malignancy within the past 5 years except adequately treated basal cell or
squamous cell skin cancer or carcinoma in situ of the cervix

- Not pregnant or nursing

- Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- No more than 1 prior adjuvant immunotherapy regimen for colon cancer

Chemotherapy:

- At least 6 months since prior adjuvant chemotherapy and recovered

- No more than 1 prior adjuvant chemotherapy regimen for colon cancer

- No prior hepatic arterial infusion chemotherapy

Endocrine therapy:

- Not specified

Radiotherapy:

- At least 1 month since prior radiotherapy

- No prior hepatic radiotherapy

Surgery:

- At least 1 month since prior surgery

- Prior surgical resection or ablation of liver metastases allowed

Other:

- No other concurrent therapy

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Primary Purpose: Treatment

Principal Investigator

Michael C. Soulen, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Abramson Cancer Center of the University of Pennsylvania

Authority:

United States: Federal Government

Study ID:

CDR0000068871

NCT ID:

NCT00023868

Start Date:

November 2001

Completion Date:

Related Keywords:

  • Colorectal Cancer
  • Metastatic Cancer
  • stage IV colon cancer
  • stage IV rectal cancer
  • recurrent colon cancer
  • recurrent rectal cancer
  • adenocarcinoma of the colon
  • adenocarcinoma of the rectum
  • liver metastases
  • Adenocarcinoma
  • Colorectal Neoplasms
  • Neoplasm Metastasis
  • Neoplasms
  • Neoplasms, Second Primary
  • Colonic Neoplasms

Name

Location

Arizona Cancer CenterTucson, Arizona  85724
University of Texas - MD Anderson Cancer CenterHouston, Texas  77030-4009
H. Lee Moffitt Cancer Center and Research InstituteTampa, Florida  33612
University of Pennsylvania Cancer CenterPhiladelphia, Pennsylvania  19104
Robert H. Lurie Comprehensive Cancer Center, Northwestern UniversityChicago, Illinois  60611
State University of New York - Upstate Medical UniversitySyracuse, New York  13210
Beth Israel Deaconess Medical CenterBoston, Massachusetts  02215
NYU School of Medicine's Kaplan Comprehensive Cancer CenterNew York, New York  10016
Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsBaltimore, Maryland  21231-2410