Brief Summary
Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. It is not yet known which chemotherapy regimen is more effective for stage III colon cancer. Randomized phase III trial to compare the effectiveness of fluorouracil plus leucovorin with or without irinotecan in treating patients who have undergone surgery for stage III colon cancer.
Brief Title
Combination Chemotherapy in Treating Patients With Stage III Colon Cancer
Detailed Description
PRIMARY OBJECTIVES:
I. Compare the overall and disease free survival of patients with stage III colon cancer treated with adjuvant fluorouracil and leucovorin calcium with or without irinotecan.
II. Assess prognostic markers and correlate their expression with disease free and overall survival of these patients.
III. Assess the influence of diet, body mass index, and physical activity on the risk of cancer recurrence and survival in these patients.
IV. Assess the influence of diet, obesity, and physical activity on the risk of toxicity associated with adjuvant therapy in these patients.
V. Determine whether pathological features (including tumor grade, tumor mitotic (proliferation) index, tumor border configuration, and host lymphoid response to tumor; and lymphatic vessel, venous vessel and perineural invasion) predict outcome in this patient population.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to lymph node involvement (1-3 vs 4 or more), histology (poorly differentiated or undifferentiated vs well or moderately differentiated), and preoperative serum CEA (less than 5.0 ng/mL vs at least 5.0 ng/mL vs unknown). Study therapy must begin within 21-56 days after surgery. Patients are randomized to one of two treatment arms:
ARM I: Patients receive leucovorin calcium IV over 2 hours and fluorouracil IV beginning 1 hour into leucovorin calcium infusion weekly for 6 weeks. Treatment is repeated every 8 weeks for 4 courses.
ARM II: Patients receive irinotecan IV over 90 minutes, followed by leucovorin calcium IV, then followed by fluorouracil IV weekly for 4 weeks. Treatment is repeated every 6 weeks for 5 courses.
Patients complete a food questionnaire at the beginning of the third course and then at 6 months after study therapy.
Patients are followed every 3 months for 2 years, every 4 months for 2 years, then annually thereafter.
PROJECTED ACCRUAL: A total of 1260 patients will be accrued for this study within 3 years.
I. Compare the overall and disease free survival of patients with stage III colon cancer treated with adjuvant fluorouracil and leucovorin calcium with or without irinotecan.
II. Assess prognostic markers and correlate their expression with disease free and overall survival of these patients.
III. Assess the influence of diet, body mass index, and physical activity on the risk of cancer recurrence and survival in these patients.
IV. Assess the influence of diet, obesity, and physical activity on the risk of toxicity associated with adjuvant therapy in these patients.
V. Determine whether pathological features (including tumor grade, tumor mitotic (proliferation) index, tumor border configuration, and host lymphoid response to tumor; and lymphatic vessel, venous vessel and perineural invasion) predict outcome in this patient population.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to lymph node involvement (1-3 vs 4 or more), histology (poorly differentiated or undifferentiated vs well or moderately differentiated), and preoperative serum CEA (less than 5.0 ng/mL vs at least 5.0 ng/mL vs unknown). Study therapy must begin within 21-56 days after surgery. Patients are randomized to one of two treatment arms:
ARM I: Patients receive leucovorin calcium IV over 2 hours and fluorouracil IV beginning 1 hour into leucovorin calcium infusion weekly for 6 weeks. Treatment is repeated every 8 weeks for 4 courses.
ARM II: Patients receive irinotecan IV over 90 minutes, followed by leucovorin calcium IV, then followed by fluorouracil IV weekly for 4 weeks. Treatment is repeated every 6 weeks for 5 courses.
Patients complete a food questionnaire at the beginning of the third course and then at 6 months after study therapy.
Patients are followed every 3 months for 2 years, every 4 months for 2 years, then annually thereafter.
PROJECTED ACCRUAL: A total of 1260 patients will be accrued for this study within 3 years.
Categories
Conditions
Adenocarcinoma of the Colon
Stage III Colon Cancer
Eligibility Criteria
Inclusion Criteria:
* Patients must have histologically documented adenocarcinoma of the colon; the gross inferior (caudad) margin of the primary tumor must lie above the peritoneal reflection; tumor must have been completely resected, including negative radial resecting margins
* There must be no history of distant metastatic disease at the time of registration
* Pathological evaluation must show Modified Astler-Coller stage C (TxN1-2M0) disease
* No previous or concurrent malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease-free for five years
* Zubrod performance status of 0-2
* Non-pregnant and not nursing, as chemotherapy is thought to present substantial risk to the fetus/infant; men and women of reproductive potential may not participate unless they have agreed to use an effective contraceptive method while in this study
* Granulocytes \>= 1,500/ul
* Platelet count \>= 100,000/ul
* Creatinine =\< 1.5 x upper limits of normal
* Bilirubin =\< upper limit of normal
* Patients must have histologically documented adenocarcinoma of the colon; the gross inferior (caudad) margin of the primary tumor must lie above the peritoneal reflection; tumor must have been completely resected, including negative radial resecting margins
* There must be no history of distant metastatic disease at the time of registration
* Pathological evaluation must show Modified Astler-Coller stage C (TxN1-2M0) disease
* No previous or concurrent malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease-free for five years
* Zubrod performance status of 0-2
* Non-pregnant and not nursing, as chemotherapy is thought to present substantial risk to the fetus/infant; men and women of reproductive potential may not participate unless they have agreed to use an effective contraceptive method while in this study
* Granulocytes \>= 1,500/ul
* Platelet count \>= 100,000/ul
* Creatinine =\< 1.5 x upper limits of normal
* Bilirubin =\< upper limit of normal
Inclusion Criteria
Inclusion Criteria:
* Patients must have histologically documented adenocarcinoma of the colon; the gross inferior (caudad) margin of the primary tumor must lie above the peritoneal reflection; tumor must have been completely resected, including negative radial resecting margins
* There must be no history of distant metastatic disease at the time of registration
* Pathological evaluation must show Modified Astler-Coller stage C (TxN1-2M0) disease
* No previous or concurrent malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease-free for five years
* Zubrod performance status of 0-2
* Non-pregnant and not nursing, as chemotherapy is thought to present substantial risk to the fetus/infant; men and women of reproductive potential may not participate unless they have agreed to use an effective contraceptive method while in this study
* Granulocytes \>= 1,500/ul
* Platelet count \>= 100,000/ul
* Creatinine =\< 1.5 x upper limits of normal
* Bilirubin =\< upper limit of normal
* Patients must have histologically documented adenocarcinoma of the colon; the gross inferior (caudad) margin of the primary tumor must lie above the peritoneal reflection; tumor must have been completely resected, including negative radial resecting margins
* There must be no history of distant metastatic disease at the time of registration
* Pathological evaluation must show Modified Astler-Coller stage C (TxN1-2M0) disease
* No previous or concurrent malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease-free for five years
* Zubrod performance status of 0-2
* Non-pregnant and not nursing, as chemotherapy is thought to present substantial risk to the fetus/infant; men and women of reproductive potential may not participate unless they have agreed to use an effective contraceptive method while in this study
* Granulocytes \>= 1,500/ul
* Platelet count \>= 100,000/ul
* Creatinine =\< 1.5 x upper limits of normal
* Bilirubin =\< upper limit of normal
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Estimated
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT00003835
Org Class
Nih
Org Full Name
National Cancer Institute (NCI)
Org Study Id
NCI-2012-01844
Overall Status
Completed
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
Phase III Intergroup Trial of Irinotecan (CPT-11) (NSC# 616348) Plus Fluorouracil/Leucovorin (5-FU/LV) Versus Fluorouracil/Leucovorin Alone After Curative Resection for Patients With Stage III Colon Cancer
Primary Outcomes
Outcome Description
The Cox proportional hazards model will be used to determine the association between each marker and time to recurrence and survival controlling for other baseline factors such as age, gender, treatment, primary tumor site, degree of differentiation.
Outcome Measure
Time to recurrence
Outcome Time Frame
From time of resection until documented disease progression, assessed up to 6 years
Outcome Description
The Cox proportional hazards model will be used to determine the association between each marker and time to recurrence and survival controlling for other baseline factors such as age, gender, treatment, primary tumor site, degree of differentiation.
Outcome Measure
Survival
Outcome Time Frame
Up to 6 years
Secondary Ids
Secondary Id
NCI-2012-01844
Secondary Id
SWOG-C89803
Secondary Id
NCCTG-C89803
Secondary Id
CDR0000066992
Secondary Id
CAN-NCIC-CO15
Secondary Id
E-89803
Secondary Id
CALGB 89803
Secondary Id
C89803
Secondary Id
U10CA031946
Start Date
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Joseph Sparano
Investigator Email
jsparano@montefiore.org
Investigator Phone
718-405-8404
Categories Mesh Debug
Gastrointestinal (GI) Cancers --- COLORECTAL NEOPLASMS
Gastrointestinal (GI) Cancers --- INTESTINAL NEOPLASMS
Gastrointestinal (GI) Cancers --- GASTROINTESTINAL NEOPLASMS
Gastrointestinal (GI) Cancers --- DIGESTIVE SYSTEM NEOPLASMS
Cancer --- NEOPLASMS BY SITE
Cancer --- NEOPLASMS
Gastrointestinal (GI) Cancers --- DIGESTIVE SYSTEM DISEASES
Digestive System --- DIGESTIVE SYSTEM DISEASES
Liver --- DIGESTIVE SYSTEM DISEASES
Gastrointestinal (GI) Cancers --- GASTROINTESTINAL DISEASES
Digestive System --- GASTROINTESTINAL DISEASES
Gastrointestinal (GI) Cancers --- COLONIC DISEASES
Digestive System --- COLONIC DISEASES
Gastrointestinal (GI) Cancers --- INTESTINAL DISEASES
Digestive System --- INTESTINAL DISEASES
MeSH Terms
COLONIC NEOPLASMS
COLORECTAL NEOPLASMS
INTESTINAL NEOPLASMS
GASTROINTESTINAL NEOPLASMS
DIGESTIVE SYSTEM NEOPLASMS
NEOPLASMS BY SITE
NEOPLASMS
DIGESTIVE SYSTEM DISEASES
GASTROINTESTINAL DISEASES
COLONIC DISEASES
INTESTINAL DISEASES
LEVOLEUCOVORIN
FLUOROURACIL
IRINOTECAN
LEUCOVORIN
FORMYLTETRAHYDROFOLATES
TETRAHYDROFOLATES
FOLIC ACID
PTERINS
PTERIDINES
HETEROCYCLIC COMPOUNDS, 2-RING
HETEROCYCLIC COMPOUNDS, FUSED-RING
HETEROCYCLIC COMPOUNDS
URACIL
PYRIMIDINONES
PYRIMIDINES
HETEROCYCLIC COMPOUNDS, 1-RING
CAMPTOTHECIN
ALKALOIDS