NCT00003594 · CITED IN SOURCE DOCUMENTS

Combination Chemotherapy in Treating Patients With Advanced Colorectal Cancer

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: COMPLETED
Registry last update: 2020-04-29

RATIONALE: 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 regimen of combination chemotherapy is most effective in treating advanced colorectal cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of various combination chemotherapy regimens in treating patients who have advanced, recurrent, or metastatic colorectal cancer that cannot be treated with surgery or radiation therapy.

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What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

No posted result sections were captured. Registered plans do not establish that a treatment works.

Who could take part

eligibility Criteria: DISEASE CHARACTERISTICS: * Histologically or cytologically confirmed locally advanced, locally recurrent, or metastatic colorectal adenocarcinoma not curable by surgery or radiotherapy * Histological or cytological requirement waived in patients who developed radiological or clinical evidence of metastatic cancer after a prior surgical resection unless: * More than 5 years has elapsed since primary surgery OR * Primary cancer was stage I or II * Site of primary lesion must be or have been confirmed endoscopically, radiologically, or surgically to be or have been in the large bowel * Measurable or evaluable disease * No CNS metastases or carcinomatous meningitis PATIENT CHARACTERISTICS: Age: * 18 and over Performance status: * ECOG 0-2 Life expectancy: * At least 12 weeks Hematopoietic: * Absolute granulocyte count at least 1,500/mm\^3 * Platelet count at least 100,000/mm\^3 * Hemoglobin at least 9.0 g/dL (transfusion allowed) Hepatic: * Bilirubin no greater than 1.5 mg/dL * AST no greater than 5 times upper limit of normal (ULN) * Alkaline phosphatase no greater than 5 times ULN Renal: * Creatinine no greater than 1.5 times ULN Cardiovascular: * No uncontrolled hypertension * No unstable angina * No symptomatic congestive heart failure * No myocardial infarction within the past 6 months * No serious uncontrolled arrhythmia * No New York Heart Association class III or IV cardiac disease Pulmonary: * No interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung * No pleural effusion or ascites that cause respiratory compromise (grade 2 or worse dyspnea) Other: * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No active or uncontrolled infection * No symptomatic sensory peripheral neuropathy * No known allergy to platinum compounds * No history of gastrointestinal bleeding unless it is determined to be acceptable by the enrolling physician * No other prior or concurrent malignancy within the past 3 years except nonmelanoma skin cancer, carcinoma in situ of the uterine cervix, or other resected malignant tumor with less than a 10% probability of tumor relapse within 3 years of diagnosis * No medical or psychiatric conditions that would preclude study * No colonic or small bowel disorders with uncontrolled symptoms of more than 3 loose stools per day * Colostomy or ileostomy allowed at investigator's discretion PRIOR CONCURRENT THERAPY: Biologic therapy: * Prior adjuvant immunotherapy for resected stage II-IV disease allowed if adjuvant therapy concluded at least 1 year before documentation of recurrent disease * No concurrent sargramostim (GM-CSF) Chemotherapy: * No prior chemotherapy for advanced colorectal cancer * No prior standard adjuvant chemotherapy for rectal cancer * Prior adjuvant fluorouracil for resected stage II-IV disease allowed if adjuvant therapy concluded at least 1 year before documentation of recurrent disease Radiotherapy: * See Disease Characteristics * At least 4 weeks since prior major radiotherapy (e.g., chest or bone palliative radiotherapy) * No prior radiotherapy to more than 15% of bone marrow * No prior standard adjuvant radiotherapy for rectal cancer Surgery: * See Disease Characteristics * At least 4 weeks since prior major surgery (e.g., laparotomy) (2 weeks for minor surgery) and recovered * Insertion of a vascular access device not considered major or minor surgery Other: * No other concurrent investigational agents
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Patients receive irinotecan IV over 90 minutes followed by leucovorin calcium IV over 15 minutes and fluorouracil IV once a week for 4 weeks followed by 2 weeks of rest. Courses repeat every 6 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity. Quality of life is assessed before treatment, during treatment (arm specific), and after completion of treatment. Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.
intervention Names
Drug: irinotecan
Drug: fluorouracil
Drug: leucovorin calcium
label
irinotecan + leucovorin + fluorouracil
type
EXPERIMENTAL
description
Patients receive oxaliplatin IV over 2 hours on day 1 and leucovorin calcium IV over 2 hours plus fluorouracil IV over 22 hours on days 1 and 2. Courses repeat every 2 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity. Quality of life is assessed before treatment, during treatment (arm specific), and after completion of treatment. Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.
intervention Names
Drug: fluorouracil
Drug: leucovorin calcium
Drug: oxaliplatin
label
oxaliplatin + leucovorin + fluorouracil
type
EXPERIMENTAL
description
Patients receive oxaliplatin IV over 2 hours and irinotecan IV over 30 minutes on day 1. Courses repeat every 3 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity. Quality of life is assessed before treatment, during treatment (arm specific), and after completion of treatment. Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.
intervention Names
Drug: irinotecan
Drug: oxaliplatin
label
oxaliplatin + irinotecan
type
EXPERIMENTAL

interventions

arm Group Labels
irinotecan + leucovorin + fluorouracil
oxaliplatin + irinotecan
name
irinotecan
type
DRUG
arm Group Labels
irinotecan + leucovorin + fluorouracil
oxaliplatin + leucovorin + fluorouracil
name
fluorouracil
type
DRUG
arm Group Labels
irinotecan + leucovorin + fluorouracil
oxaliplatin + leucovorin + fluorouracil
name
leucovorin calcium
type
DRUG
arm Group Labels
oxaliplatin + irinotecan
oxaliplatin + leucovorin + fluorouracil
name
oxaliplatin
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 1691
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

measure
time to progression
time Frame
Up to 5 years

secondary Outcomes

measure
overall survival
time Frame
Up to 5 years
measure
time to treatment failure
time Frame
Up to 5 years
measure
response rate
time Frame
Up to 5 years
measure
quality of life
time Frame
Up to 5 years

Full study description

brief Summary: RATIONALE: 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 regimen of combination chemotherapy is most effective in treating advanced colorectal cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of various combination chemotherapy regimens in treating patients who have advanced, recurrent, or metastatic colorectal cancer that cannot be treated with surgery or radiation therapy.
detailed Description: OBJECTIVES: * Compare the time to progression in patients with locally advanced, locally recurrent, or metastatic colorectal adenocarcinoma treated with combinations of oxaliplatin, fluorouracil, leucovorin calcium, and irinotecan. * Compare the quality of life, response rate, time to treatment failure, and overall survival in patients treated with these regimens. * Compare the toxicity of these regimens in these patients. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to ECOG performance status (0-1 vs 2), prior adjuvant chemotherapy (yes vs no), prior immunotherapy (yes vs no), and age (under 65 vs 65 and over). Patients are randomized to one of three treatment arms. Only arm II remains open to accrual. * Arm I (Saltz regimen): Patients receive irinotecan IV over 90 minutes followed by leucovorin calcium IV over 15 minutes and fluorouracil IV once a week for 4 weeks followed by 2 weeks of rest. Courses repeat every 6 weeks. (Arm I closed to accrual as of March 15, 2002.) * Arm II (FOLFOX4 regimen): Patients receive oxaliplatin IV over 2 hours on day 1 and leucovorin calcium IV over 2 hours plus fluorouracil IV over 22 hours on days 1 and 2. Courses repeat every 2 weeks. * Arm III (oxaliplatin plus irinotecan): Patients receive oxaliplatin IV over 2 hours and irinotecan IV over 30 minutes on day 1. Courses repeat every 3 weeks. (Arm III closed to accrual as of March 15, 2002.) Treatment continues in the absence of disease progression or unacceptable toxicity. Quality of life is assessed before treatment, during treatment (arm specific), and after completion of treatment. Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 825 patients (275 per arm) have been accrued for this study thus far. Additional patients are being accrued on arm II. (Arms I and III closed to accrual as of March 15, 2002.)

Source references

references

citation
Franko J, Shi Q, Goldman CD, Pockaj BA, Nelson GD, Goldberg RM, Pitot HC, Grothey A, Alberts SR, Sargent DJ. Treatment of colorectal peritoneal carcinomatosis with systemic chemotherapy: a pooled analysis of north central cancer treatment group phase III trials N9741 and N9841. J Clin Oncol. 2012 Jan 20;30(3):263-7. doi: 10.1200/JCO.2011.37.1039. Epub 2011 Dec 12.
pmid
22162570
type
BACKGROUND
citation
An MW, Mandrekar SJ, Branda ME, Hillman SL, Adjei AA, Pitot HC, Goldberg RM, Sargent DJ. Comparison of continuous versus categorical tumor measurement-based metrics to predict overall survival in cancer treatment trials. Clin Cancer Res. 2011 Oct 15;17(20):6592-9. doi: 10.1158/1078-0432.CCR-11-0822. Epub 2011 Aug 31.
pmid
21880789
type
BACKGROUND
citation
Campbell ME, Mandrekar SJ, Hillman SL, et al.: What is the added value of actual tumor measurements (TM) in predicting overall survival (OS)? The North Central Cancer Treatment Group (NCCTG) findings. [Abstract] J Clin Oncol 26 (Suppl 15): A-6520, 2008.
type
BACKGROUND
citation
Grothey A, Hedrick EE, Mass RD, Sarkar S, Suzuki S, Ramanathan RK, Hurwitz HI, Goldberg RM, Sargent DJ. Response-independent survival benefit in metastatic colorectal cancer: a comparative analysis of N9741 and AVF2107. J Clin Oncol. 2008 Jan 10;26(2):183-9. doi: 10.1200/JCO.2007.13.8099.
pmid
18182660
type
BACKGROUND
citation
Grothey A, Hedrick EE, Mass RD, et al.: Response rate using conventional criteria is a poor surrogate for clinical benefit on progression-free (PFS) and overall survival (OS) in metastatic colorectal cancer (mCRC): a comparative analysis of N9741 and AVF2107. [Abstract] J Clin Oncol 24 (Suppl 18): A-3516, 2006.
type
BACKGROUND
citation
Goldberg R. Oxaliplatin in colorectal cancer: current studies. Oncology (Williston Park). 2000 Dec;14(12 Suppl 11):42-7.
pmid
11204663
type
BACKGROUND
citation
Heun JM, Grothey A, Branda ME, Goldberg RM, Sargent DJ. Tumor status at 12 weeks predicts survival in advanced colorectal cancer: findings from NCCTG N9741. Oncologist. 2011;16(6):859-67. doi: 10.1634/theoncologist.2011-0064. Epub 2011 May 31.
pmid
21632455
type
RESULT
citation
Ng K, Sargent DJ, Goldberg RM, Meyerhardt JA, Green EM, Pitot HC, Hollis BW, Pollak MN, Fuchs CS. Vitamin D status in patients with stage IV colorectal cancer: findings from Intergroup trial N9741. J Clin Oncol. 2011 Apr 20;29(12):1599-606. doi: 10.1200/JCO.2010.31.7255. Epub 2011 Mar 21.
pmid
21422438
type
RESULT
citation
Goldberg RM, Sargent DJ, McLeod H. Leveraging learning from a phase III colorectal cancer clinical trial: outcomes, methodology, meta-analysis and pharmacogenetics. Trans Am Clin Climatol Assoc. 2010;121:21-32; discussion 32-3.
pmid
20697547
type
RESULT
citation
McLeod HL, Sargent DJ, Marsh S, Green EM, King CR, Fuchs CS, Ramanathan RK, Williamson SK, Findlay BP, Thibodeau SN, Grothey A, Morton RF, Goldberg RM. Pharmacogenetic predictors of adverse events and response to chemotherapy in metastatic colorectal cancer: results from North American Gastrointestinal Intergroup Trial N9741. J Clin Oncol. 2010 Jul 10;28(20):3227-33. doi: 10.1200/JCO.2009.21.7943. Epub 2010 Jun 7.
pmid
20530282
type
RESULT
citation
Goldberg RM, Sargent DJ, Morton RF, Green E, Sanoff HK, McLeod H, Buckner J. NCCTG Study N9741: leveraging learning from an NCI Cooperative Group phase III trial. Oncologist. 2009 Oct;14(10):970-8. doi: 10.1634/theoncologist.2009-0175. Epub 2009 Oct 14.
pmid
19828593
type
RESULT
citation
Sanoff HK, Sargent DJ, Green EM, McLeod HL, Goldberg RM. Racial differences in advanced colorectal cancer outcomes and pharmacogenetics: a subgroup analysis of a large randomized clinical trial. J Clin Oncol. 2009 Sep 1;27(25):4109-15. doi: 10.1200/JCO.2009.21.9527. Epub 2009 Jul 27.
pmid
19636001
type
RESULT