Ignite Creation Date:
2024-05-05 @ 11:30 AM
Last Modification Date:
2024-10-26 @ 9:09 AM
Study NCT ID:
NCT00068692
Status:
COMPLETED
Last Update Posted:
2018-12-04
First Post:
2003-09-10
Brief Title:
Comparison of Adjuvant Chemotherapy Regimens in Treating Stage IIIII Rectal Cancer
Sponsor:
National Cancer Institute NCI
Organization:
National Cancer Institute NCI
Study Overview
Official Title:
Intergroup Randomized Phase III Study of Postoperative Irinotecan 5-Fluorouracil and Leucovorin vs Oxaliplatin 5-Fluorouracil and Leucovorin vs 5-Fluorouracil and Leucovorin for Patients With Stage II or III Rectal Cancer Receiving Either Preoperative Radiation and 5-Fluorouracil or Postoperative Radiation and 5-Fluorouracil
Status:
COMPLETED
Status Verified Date:
2018-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This randomized phase III trial is comparing the effectiveness of three adjuvant combination chemotherapy regimens in treating patients who are receiving radiation therapy and fluorouracil either before or after surgery for stage II or stage III rectal cancer Drugs used in chemotherapy such as irinotecan fluorouracil leucovorin and oxaliplatin use different ways to stop tumor cells from dividing so they stop growing or die Radiation therapy uses high-energy x-rays to damage tumor cells It is not yet known which adjuvant combination chemotherapy regimen is more effective in treating patients who are receiving radiation therapy and fluorouracil either before or after surgery for rectal cancer
Detailed Description:
PRIMARY OBJECTIVES
I To compare the overall survival of patients treated with irinotecan 5-FU and leucovorin versus those treated with oxaliplatin leucovorin and 5-FU versus those treated with leucovorin and 5-FU for patients with stage II and III rectal cancer
SECONDARY OBJECTIVES
I To determine sphincter preservation tolerance of treatment and patterns of failure
II To describe patterns of failures
OTHER PRE-SPECIFIED OBJECTIVES
ITo prospectively assess rectal function using the Patient Bowel FunctionUniscale questionnaire and the FACT Diarrhea Subscale in patients treated with an adjuvant program of pelvic radiation therapy and chemotherapy
II To correlate expression of key targets for 5-FU leucovorin oxaliplatin and irinotecan from tumor tissue biopsies with treatment efficacy III To correlate tumor molecular prognostic markers with survival IV To determine physician preference in regard to the radiation-chemotherapy sequence in the Intergroup
OUTLINE This is a randomized multicenter study Patients are stratified according to ECOG performance status 0 vs 1 chemotherapyradiotherapy sequence preoperative vs postoperative and risk group high risk T3 N M0 or T4 any N M0 vs low risk T1-2 N M0 or T3 N0 M0 Patients are treated in 1 of 2 groups according to physician preference and then randomized to 1 of 3 treatment arms
GROUP I preoperative chemoradiotherapy and additional adjuvant chemotherapy Preoperative chemoradiotherapy Patients receive 1 of 3 treatment regimens determined by the treating physician
REGIMEN A radiotherapy and fluorouracil Patients undergo external beam radiotherapy once daily 5 days a week for 5 12 weeks total of 28 fractions Patients also receive concurrent fluorouracil intravenously IV continuously 7 days a week for 5 12 weeks
REGIMEN B radiotherapy fluorouracil and leucovorin calcium Patients undergo external beam radiotherapy as in regimen A Patients also receive concurrent fluorouracil IV and leucovorin calcium IV continuously for 4 days on weeks 1 and 5
REGIMEN C radiotherapy and capecitabine Patients undergo external beam radiotherapy as in regimen A Patients also receive concurrent oral capecitabine twice daily for 5 12 weeks
NOTE Regimen C is allowed only for patients enrolled on protocol NSABP-R-04
Surgery Within 21-56 days after the completion of chemoradiotherapy patients undergo surgical resection
Additional adjuvant chemotherapy Within 21-56 days after complete surgical resection patients are randomized to 1 of 3 treatment arms
ARM I Patients receive irinotecan IV over 90 minutes and leucovorin calcium IV over 2 hours followed immediately by fluorourcil IV bolus on day 1 Patients also receive fluorouracil IV continuously over 46 hours beginning on day 1 Treatment repeats every 2 weeks for 8 courses
ARM II Patients receive oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours followed immediately by fluorourcil IV bolus on day 1 Patients also receive fluorouracil IV continuously over 46 hours beginning on day 1 Treatment repeats every 2 weeks for 8 courses
ARM III Patients receive leucovorin calcium IV over 2 hours and fluorouracil IV over 1 hour on days 1 8 15 22 29 and 36 Treatment repeats every 8 weeks for 3 courses
In all arms treatment continues in the absence of disease progression or unacceptable toxicity
GROUP 2 postoperative chemoradiotherapy and additional adjuvant chemotherapy Within 21-56 days after complete surgical resection patients are randomized to 1 of 3 treatment arms
ARM I Patients receive irinotecan leucovorin calcium and fluorouracil as in group 1 arm I for 4 courses
ARM II Patients receive oxaliplatin leucovorin calcium and fluorouracil as in group 1 arm II for 4 courses
ARM III Patients receive leucovorin calcium and fluorouracil as in group 1 arm III for 1 course
Within 4 weeks after the completion of chemotherapy all patients undergo concurrent pelvic chemoradiotherapy as described in group 1 preoperative chemoradiotherapy Regimen A B or C followed 4-6 weeks later by 4 additional courses of adjuvant chemotherapy for arms I and II and 2 additional courses of adjuvant chemotherapy for arm III
Treatment continues in the absence of disease progression or unacceptable toxicity
Patients are followed every 3 months for 3 years every 6 months for 2 years and then annually for 5 years
I To compare the overall survival of patients treated with irinotecan 5-FU and leucovorin versus those treated with oxaliplatin leucovorin and 5-FU versus those treated with leucovorin and 5-FU for patients with stage II and III rectal cancer
SECONDARY OBJECTIVES
I To determine sphincter preservation tolerance of treatment and patterns of failure
II To describe patterns of failures
OTHER PRE-SPECIFIED OBJECTIVES
ITo prospectively assess rectal function using the Patient Bowel FunctionUniscale questionnaire and the FACT Diarrhea Subscale in patients treated with an adjuvant program of pelvic radiation therapy and chemotherapy
II To correlate expression of key targets for 5-FU leucovorin oxaliplatin and irinotecan from tumor tissue biopsies with treatment efficacy III To correlate tumor molecular prognostic markers with survival IV To determine physician preference in regard to the radiation-chemotherapy sequence in the Intergroup
OUTLINE This is a randomized multicenter study Patients are stratified according to ECOG performance status 0 vs 1 chemotherapyradiotherapy sequence preoperative vs postoperative and risk group high risk T3 N M0 or T4 any N M0 vs low risk T1-2 N M0 or T3 N0 M0 Patients are treated in 1 of 2 groups according to physician preference and then randomized to 1 of 3 treatment arms
GROUP I preoperative chemoradiotherapy and additional adjuvant chemotherapy Preoperative chemoradiotherapy Patients receive 1 of 3 treatment regimens determined by the treating physician
REGIMEN A radiotherapy and fluorouracil Patients undergo external beam radiotherapy once daily 5 days a week for 5 12 weeks total of 28 fractions Patients also receive concurrent fluorouracil intravenously IV continuously 7 days a week for 5 12 weeks
REGIMEN B radiotherapy fluorouracil and leucovorin calcium Patients undergo external beam radiotherapy as in regimen A Patients also receive concurrent fluorouracil IV and leucovorin calcium IV continuously for 4 days on weeks 1 and 5
REGIMEN C radiotherapy and capecitabine Patients undergo external beam radiotherapy as in regimen A Patients also receive concurrent oral capecitabine twice daily for 5 12 weeks
NOTE Regimen C is allowed only for patients enrolled on protocol NSABP-R-04
Surgery Within 21-56 days after the completion of chemoradiotherapy patients undergo surgical resection
Additional adjuvant chemotherapy Within 21-56 days after complete surgical resection patients are randomized to 1 of 3 treatment arms
ARM I Patients receive irinotecan IV over 90 minutes and leucovorin calcium IV over 2 hours followed immediately by fluorourcil IV bolus on day 1 Patients also receive fluorouracil IV continuously over 46 hours beginning on day 1 Treatment repeats every 2 weeks for 8 courses
ARM II Patients receive oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours followed immediately by fluorourcil IV bolus on day 1 Patients also receive fluorouracil IV continuously over 46 hours beginning on day 1 Treatment repeats every 2 weeks for 8 courses
ARM III Patients receive leucovorin calcium IV over 2 hours and fluorouracil IV over 1 hour on days 1 8 15 22 29 and 36 Treatment repeats every 8 weeks for 3 courses
In all arms treatment continues in the absence of disease progression or unacceptable toxicity
GROUP 2 postoperative chemoradiotherapy and additional adjuvant chemotherapy Within 21-56 days after complete surgical resection patients are randomized to 1 of 3 treatment arms
ARM I Patients receive irinotecan leucovorin calcium and fluorouracil as in group 1 arm I for 4 courses
ARM II Patients receive oxaliplatin leucovorin calcium and fluorouracil as in group 1 arm II for 4 courses
ARM III Patients receive leucovorin calcium and fluorouracil as in group 1 arm III for 1 course
Within 4 weeks after the completion of chemotherapy all patients undergo concurrent pelvic chemoradiotherapy as described in group 1 preoperative chemoradiotherapy Regimen A B or C followed 4-6 weeks later by 4 additional courses of adjuvant chemotherapy for arms I and II and 2 additional courses of adjuvant chemotherapy for arm III
Treatment continues in the absence of disease progression or unacceptable toxicity
Patients are followed every 3 months for 3 years every 6 months for 2 years and then annually for 5 years
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| U10CA021115 | NIH | ECOG-ACRIN Cancer Research Group | httpsreporternihgovquickSearchU10CA021115 |
| NCI-2012-02959 | REGISTRY | None | None |
| E3201 | OTHER | None | None |