Comparison of Adjuvant Chemotherapy Regimens in Treating Patients With Stage II or Stage III Rectal Cancer Who Are Receiving Radiation Therapy and Fluorouracil Before or After Surgery

This study has been terminated.
(Administratively complete.)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00068692
First received: September 10, 2003
Last updated: February 26, 2013
Last verified: February 2013
  Purpose

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


Condition Intervention Phase
Mucinous Adenocarcinoma of the Rectum
Recurrent Rectal Cancer
Signet Ring Adenocarcinoma of the Rectum
Stage IIA Rectal Cancer
Stage IIB Rectal Cancer
Stage IIC Rectal Cancer
Stage IIIA Rectal Cancer
Stage IIIB Rectal Cancer
Stage IIIC Rectal Cancer
Stage IVA Rectal Cancer
Stage IVB Rectal Cancer
Drug: capecitabine
Drug: fluorouracil
Drug: leucovorin calcium
Drug: irinotecan hydrochloride
Drug: oxaliplatin
Radiation: external beam radiation therapy
Other: laboratory biomarker analysis
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Overall survival [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Sphincter preservation [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
  • Tolerance of treatment [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
  • Patterns of failure [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]

Enrollment: 3000
Study Start Date: October 2003
Estimated Primary Completion Date: January 2100 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group I, Arm I
Patients receive 1 of 3 preoperative chemoradiotherapy treatment regimens, determined by the treating physician. Within 21-56 days after the completion of chemoradiotherapy, patients undergo surgical resection. Patients receive irinotecan IV over 90 minutes and leucovorin calcium IV over 2 hours followed immediately by fluorourcil IV bolus on day 1. Treatment continues in the absence of disease progression or unacceptable toxicity.
Drug: capecitabine
Given orally
Other Names:
  • CAPE
  • Ro 09-1978/000
  • Xeloda
Drug: fluorouracil
Given IV
Other Names:
  • 5-fluorouracil
  • 5-Fluracil
  • 5-FU
Drug: leucovorin calcium
Given IV
Other Names:
  • CF
  • CFR
  • LV
Drug: irinotecan hydrochloride
Given IV
Other Names:
  • Campto
  • Camptosar
  • CPT-11
  • irinotecan
  • U-101440E
Radiation: external beam radiation therapy
Undergo external beam radiation therapy
Other Name: EBRT
Other: laboratory biomarker analysis
Correlative studies
Experimental: Group I, Arm II
Patients receive 1 of 3 preoperative chemoradiotherapy treatment regimens, determined by the treating physician. Within 21-56 days after the completion of chemoradiotherapy, patients undergo surgical resection. 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. Treatment continues in the absence of disease progression or unacceptable toxicity.
Drug: capecitabine
Given orally
Other Names:
  • CAPE
  • Ro 09-1978/000
  • Xeloda
Drug: fluorouracil
Given IV
Other Names:
  • 5-fluorouracil
  • 5-Fluracil
  • 5-FU
Drug: leucovorin calcium
Given IV
Other Names:
  • CF
  • CFR
  • LV
Drug: oxaliplatin
Given IV
Other Names:
  • 1-OHP
  • Dacotin
  • Dacplat
  • Eloxatin
  • L-OHP
Radiation: external beam radiation therapy
Undergo external beam radiation therapy
Other Name: EBRT
Other: laboratory biomarker analysis
Correlative studies
Experimental: Group I, Arm III
Patients receive 1 of 3 preoperative chemoradiotherapy treatment regimens, determined by the treating physician. Within 21-56 days after the completion of chemoradiotherapy, patients undergo surgical resection. 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. Treatment continues in the absence of disease progression or unacceptable toxicity.
Drug: capecitabine
Given orally
Other Names:
  • CAPE
  • Ro 09-1978/000
  • Xeloda
Drug: fluorouracil
Given IV
Other Names:
  • 5-fluorouracil
  • 5-Fluracil
  • 5-FU
Drug: leucovorin calcium
Given IV
Other Names:
  • CF
  • CFR
  • LV
Drug: irinotecan hydrochloride
Given IV
Other Names:
  • Campto
  • Camptosar
  • CPT-11
  • irinotecan
  • U-101440E
Radiation: external beam radiation therapy
Undergo external beam radiation therapy
Other Name: EBRT
Other: laboratory biomarker analysis
Correlative studies
Experimental: Group II, Arm I

Patients receive irinotecan, leucovorin calcium, and fluorouracil as in group 1, arm I for 4 courses. 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.

Drug: capecitabine
Given orally
Other Names:
  • CAPE
  • Ro 09-1978/000
  • Xeloda
Drug: fluorouracil
Given IV
Other Names:
  • 5-fluorouracil
  • 5-Fluracil
  • 5-FU
Drug: leucovorin calcium
Given IV
Other Names:
  • CF
  • CFR
  • LV
Drug: irinotecan hydrochloride
Given IV
Other Names:
  • Campto
  • Camptosar
  • CPT-11
  • irinotecan
  • U-101440E
Radiation: external beam radiation therapy
Undergo external beam radiation therapy
Other Name: EBRT
Other: laboratory biomarker analysis
Correlative studies
Experimental: Group II, Arm II

Patients receive oxaliplatin, leucovorin calcium, and fluorouracil as in group 1, arm II for 4 courses. 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.

Drug: capecitabine
Given orally
Other Names:
  • CAPE
  • Ro 09-1978/000
  • Xeloda
Drug: fluorouracil
Given IV
Other Names:
  • 5-fluorouracil
  • 5-Fluracil
  • 5-FU
Drug: leucovorin calcium
Given IV
Other Names:
  • CF
  • CFR
  • LV
Drug: oxaliplatin
Given IV
Other Names:
  • 1-OHP
  • Dacotin
  • Dacplat
  • Eloxatin
  • L-OHP
Radiation: external beam radiation therapy
Undergo external beam radiation therapy
Other Name: EBRT
Other: laboratory biomarker analysis
Correlative studies
Experimental: Group II, 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.
Drug: capecitabine
Given orally
Other Names:
  • CAPE
  • Ro 09-1978/000
  • Xeloda
Drug: fluorouracil
Given IV
Other Names:
  • 5-fluorouracil
  • 5-Fluracil
  • 5-FU
Drug: leucovorin calcium
Given IV
Other Names:
  • CF
  • CFR
  • LV
Radiation: external beam radiation therapy
Undergo external beam radiation therapy
Other Name: EBRT
Other: laboratory biomarker analysis
Correlative studies

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • GROUP I: Patients must have histologically proven adenocarcinoma of the rectum with no distant metastases; clinical staging is required (T3N0M0, T4N0M0, TanyN1-3M0)
  • GROUP I: Patients must not have evidence of tumor outside of the pelvis including liver metastases, peritoneal seeding, or metastatic inguinal lymphadenopathy
  • GROUP I: Patients must have ECOG performance status 0-1
  • GROUP I: The distal border of the tumor must be at or below the peritoneal reflection, defined as within 12 centimeters of anal verge by proctoscopic examination. In addition, patients who have had a portion of their tumors confirmed to be below the peritoneal reflection at the time of surgery are eligible regardless of the distance determined by endoscopy
  • GROUP I: Transmural penetration of tumor through the muscularis propria must be demonstrated by CT scan, endo-rectal ultrasound or MRI
  • GROUP I: Tumors must be defined prospectively by the surgeon as clinically resectable or not

    • Clinically resectable tumors will be defined by the surgeon as not fixed and completely resectable with negative margins based on the routine examination of the non-anesthetized patient
    • Before pre-op treatment, the surgeon should estimate and record the type of resection anticipated: APR, LAR or LAR/coloanal anastomosis
  • GROUP I: The tumor may be clinically fixed or initially not completely resectable, clinical stage T4 N0-2 M0 based on the presence of at least one of the following criteria:

    • Clinically fixed tumors on rectal examination with tumor adherent to the pelvic sidewall or sacrum
    • Hydronephrosis on CT scan or IVP or ureteric or bladder invasion as documented by cystoscopy and cytology or biopsy, or invasion into prostate
    • Vaginal or uterine involvement
  • GROUP I: Patients must not have received prior chemotherapy or pelvic irradiation therapy
  • GROUP I: Patients must not have a previous or concurrent malignancy, with the exception of:

    • Nonmelanoma skin cancer or in situ cervical cancer
    • Treated non-pelvic cancer from which the patient has been continuously disease-free more than five years
  • GROUP I: Patients must not have an active inflammatory bowel disease or other serious medical illness which might limit the ability of the patient to receive protocol therapy
  • GROUP I: Female patients must not be pregnant or breast-feeding; all females of childbearing potential must have a blood or urine test within 2 weeks prior to registration to rule out pregnancy
  • GROUP I: Sexually-active women of childbearing potential and sexually active males are strongly advised to use an accepted and effective method of contraception
  • GROUP II: Patients must have had histologically proven adenocarcinoma of the rectum with no distant metastases; pathologic staging is required (T3N0M0, T4N0M0, TanyN1-3M0)
  • GROUP II: Patients must not have evidence of tumor outside of the pelvis including liver metastases, peritoneal seeding, or metastatic inguinal lymphadenopathy
  • GROUP II: Patients must have ECOG performance status 0-1
  • GROUP II: The distal border of the tumor must have been at or below the peritoneal reflection, defined as within 12 centimeters of anal verge by proctoscopic examination; in addition, patients who have had a portion of their tumors confirmed to be below the peritoneal reflection at the time of the surgery are eligible regardless of the distance determined by endoscopy
  • GROUP II: Patients must not have received prior chemotherapy or pelvic irradiation therapy
  • GROUP II: Patients must not have a previous or concurrent malignancy, with the exception of:

    • Non-melanoma skin cancer or in situ cervical cancer
    • Treated non-pelvic cancer from which the patient has been continuously disease-free more than five years
  • GROUP II: Patients must not have an active inflammatory bowel disease or other serious medical illness which might limit the ability of the patient to receive protocol therapy
  • GROUP II: Female patients must not be pregnant or breast-feeding because of the potentially teratogenic and abortifacient effects of this regimen and there is no information on the excretion of the agents or their metabolites into breast milk; all females of childbearing potential must have a blood or urine test within 2 weeks prior to registration to rule out pregnancy
  • GROUP II: Sexually active women of childbearing potential and sexually active males are strongly advised to use an accepted and effective method of contraception
  • RANDOMIZATION: Patients must have a completely resected tumor and be within 21 - 56 days from the date of surgery
  • RANDOMIZATION: Patients who received combination chemotherapy/radiation prior to randomization (Group I) must have had a minimum radiation dose of 50.4 Gy
  • RANDOMIZATION: Patients must have ECOG performance status 0-1
  • RANDOMIZATION: Creatinine =< 1.5 x ULN obtained =< 4 weeks prior to randomization
  • RANDOMIZATION: Bilirubin =< 1.5 x ULN
  • RANDOMIZATION: SGOT (AST) =< 3 x ULN obtained =< 4 weeks prior to randomization
  • RANDOMIZATION: Absolute neutrophil count >= 1500/mm3
  • RANDOMIZATION: Platelet count >= 100,000/mm3 =< 4 weeks prior to randomization
  • RANDOMIZATION: Patients must not have an active inflammatory bowel disease or other serious medical illness which might limit the ability of the patient to receive protocol therapy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00068692

Locations
United States, Massachusetts
Eastern Cooperative Oncology Group
Boston, Massachusetts, United States, 02215
Sponsors and Collaborators
Investigators
Principal Investigator: Al Benson Eastern Cooperative Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00068692     History of Changes
Other Study ID Numbers: NCI-2012-02959, E3201, U10CA021115, CDR0000327815
Study First Received: September 10, 2003
Last Updated: February 26, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Adenocarcinoma
Rectal Neoplasms
Adenocarcinoma, Mucinous
Cystadenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Neoplasms, Cystic, Mucinous, and Serous
Fluorouracil
Capecitabine
Oxaliplatin
Irinotecan
Camptothecin
Leucovorin
Levoleucovorin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents

ClinicalTrials.gov processed this record on July 29, 2014