Rectal Mucinous AdenocarcinomaPhase 3NCT00068692

Comparison of Adjuvant Chemotherapy Regimens in Treating Stage II/III Rectal Cancer

A Phase 3 study testing Radiotherapy, Fluorouracil and Leucovorin Calcium in people with Rectal Mucinous Adenocarcinoma and Rectal Signet Ring Cell Adenocarcinoma, run by National Cancer Institute (NCI) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Rectal Mucinous Adenocarcinoma, Rectal Signet Ring Cell Adenocarcinoma, Recurrent Rectal Carcinoma
What is being tested?: Radiotherapy, Fluorouracil and Leucovorin Calcium
Type of treatment: Injection or infusion, Surgery or procedure
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 225 participants
Where: 1 siteUnited States
Study dates: 15 Oct 2003to 15 Nov 2016
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Patients must have histologically proven adenocarcinoma of the rectum with no distant metastases. Clinical staging is required (T3N0M0, T4N0M0, TanyN1-3M0).
Patients must not have evidence of tumor outside of the pelvis including liver metastases, peritoneal seeding, or metastatic inguinal lymphadenopathy.
The distal border of the tumor must be at or below the peritoneal reflection, defined as within 12 cm 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.
Transmural penetration of tumor through the muscularis propria must be demonstrated by CT scan, endo-rectal ultrasound or MRI.
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.

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Before pre-op treatment, the surgeon should estimate and record the type of resection anticipated: APR, LAR or LAR/coloanal anastomosis.
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.
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 for >5 years.
Patients must have ECOG performance status 0-1.
Patients must be > 18 years of age.
All females of childbearing potential must have a blood or urine test within 2 weeks prior to registration to rule out pregnancy.
Sexually-active women of childbearing potential and sexually active males are strongly advised to use an accepted and effective method of contraception
Patients must have had histologically proven adenocarcinoma of the rectum with no distant metastases. Pathologic staging is required (T3N0M0, T4N0M0, TanyN1-3M0).
Patients must not have evidence of tumor outside of the pelvis including liver metastases, peritoneal seeding, or metastatic inguinal lymphadenopathy.
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.
Patients must not have received prior chemotherapy or pelvic irradiation therapy.
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 for >5 years.
Patients must have ECOG performance status 0-1.
Patients must be > 18 years of age.
All females of childbearing potential must have a blood or urine test within 2 weeks prior to registration to rule out pregnancy.
Sexually active women of childbearing potential and sexually active males are strongly advised to use an accepted and effective method of contraception.
Patients must have a completely resected tumor and be within 21-56 days from the date of surgery.
Patients who received combination chemotherapy/XRT prior to randomization (Group I) must have had a minimum radiation dose of 50.4 Gy.
Patients must have ECOG performance status 0-1.
Patients must have adequate renal function (creatinine < 1.5 x ULN) obtained < 4 weeks prior to randomization.
Patients must have adequate hepatic function (bilirubin < 1.5 x ULN, SGOT (AST) < 3 x ULN) obtained < 4 weeks prior to randomization).
Patients must have absolute neutrophil count > 1500/mm3 and platelet count > 100,000/mm3 < 4 weeks prior to randomization.

Who cannot join

Patients have received prior chemotherapy or pelvic irradiation therapy.
Female patients must not be pregnant or breast-feeding.
Patients 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 (Post-operative) Registration
Patients have an active inflammatory bowel disease or other serious medical illness which might limit the ability of the patient to receive protocol therapy.
Female patients are pregnant or breast-feeding.
Randomization (Groups I and II)
Patients have an active inflammatory bowel disease or other serious medical illness which might limit the ability of the patient to receive protocol therapy.

Trial locations and contacts

1 site in 1 country.

United States1 site

Eastern Cooperative Oncology Group
Boston, Massachusetts, 02215

Other trials in United States

About this study

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

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.

Read the detailed description

PRIMARY OBJECTIVES:

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:

To determine sphincter preservation, tolerance of treatment and patterns of failure.

II. To describe patterns of failures

OTHER PRE-SPECIFIED OBJECTIVES:

I.To prospectively assess rectal function using the Patient Bowel Function/Uniscale 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), chemotherapy/radiotherapy 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 1/2 weeks (total of 28 fractions). Patients also receive concurrent fluorouracil intravenously (IV) continuously 7 days a week for 5 1/2 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 1/2 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.

Conditions: Rectal Mucinous Adenocarcinoma, Rectal Signet Ring Cell Adenocarcinoma, Recurrent Rectal Carcinoma, Stage IIA Rectal Cancer AJCC v7, Stage IIB Rectal Cancer AJCC v7, Stage IIC Rectal Cancer AJCC v7
Being tested: Radiotherapy, Fluorouracil, Leucovorin Calcium, Oxaliplatin, Irinotecan
Keywords: rectal cancer, chemotherapy, irinotecan, oxaliplatin
Medical subject headings: Rectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

RadiotherapyRadiation
Also called Definitive Radiation Therapy, EBRT, External Beam Radiotherapy, external radiation
Undergo external beam radiation therapy
FluorouracilDrug
Also called Efudex, 5-FU, 5-Fluorouracil, Adrucil
Given IV
Leucovorin CalciumDrug
Also called Leucovorin, Wellcovorin, citrovorun factor, folinic acid
Given IV
OxaliplatinDrug
Also called 1-OHP, Dacplat, Eloxatin, Eloxatine
Given IV
IrinotecanDrug
Also called Camptosar, CPT-11, Camptothecin-11
Given IV

Study groups in NCT00068692
Study group	Role	What they receive
Group I, Arm I	Experimental	Patients receive 1 of 3 preoperative chemo and radiotherapy 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. Receives: Radiation: Radiotherapy; Drug: Fluorouracil; Drug: Leucovorin Calcium; Drug: Irinotecan
Group I, Arm II	Experimental	Patients receive 1 of 3 preoperative chemo and radiotherapy 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. Receives: Radiation: Radiotherapy; Drug: Fluorouracil; Drug: Leucovorin Calcium; Drug: Oxaliplatin
Group I, Arm III	Experimental	Patients receive 1 of 3 preoperative chemo and radiotherapy 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. Receives: Radiation: Radiotherapy; Drug: Fluorouracil; Drug: Leucovorin Calcium
Group II, Arm I	Experimental	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 chemo and radiotherapy 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. Receives: Radiation: Radiotherapy; Drug: Fluorouracil; Drug: Leucovorin Calcium; Drug: Irinotecan
Group II, Arm II	Experimental	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 chemo and radiotherapy 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. Receives: Radiation: Radiotherapy; Drug: Fluorouracil; Drug: Leucovorin Calcium; Drug: Oxaliplatin
Group II, Arm III	Experimental	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 chemo and radiotherapy 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. Receives: Radiation: Radiotherapy; Drug: Fluorouracil; Drug: Leucovorin Calcium

What is being measured

The primary outcome is the main question the study is designed to answer.

3-year Overall Survival Rate
Overall survival (OS) was defined as time from randomization to death from any cause. 3-year OS rate was estimated using Kaplan-Meier method.
Measured: assessed every 3 months withihn 2 years of study entry, every 6 monhts between years 3-5 and then annually for 5 years, estimated at 3 years

Secondary outcomes (3)

3-year Disease Free Survival
Disease free survival (DFS) was defined as time from randomization to recurrence, second invasive primary cancer and death from any cause, whichever occurred first. 3-year DFS rate was estimated using Kaplan-Meier method.
Measured: assessed every 3 months withihn 2 years of study entry, every 6 monhts between years 3-5 and then annually for 5 years, estimated at 3 years
Proportion of Sphincter Preservation
Proportion of sphincter preservation was defined as number of patients with sphincter preservation divided by total number of patients randomized to the arm
Measured: assessed at primary surgery time
Failure Pattern
Type of failures (local/regional recurrence vs. distant recurrence vs. concurrent recurrence vs. second primary cancer vs. deaths) in the analysis population
Measured: assessed every 3 months withihn 2 years of study entry, every 6 monhts between years 3-5 and then annually for 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

15 Oct 200315 Nov 2016

First posted11 Sep 2003 (estimated)
Study start15 Oct 2003
Primary completion15 Nov 2016
Study completion15 Nov 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Rectal Mucinous AdenocarcinomaStudies of the same condition, open and under way.
More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 225 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00068692
Sponsor's protocol ID: NCI-2012-02959
Other IDs: NCI-2012-02959, E3201, U10CA021115
Status last verified: Dec 2018
First submitted: 10 Sep 2003
Last updated: 4 Dec 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: Individual patient data will be shared upon approval

Publications

Kam AE, Zhao F, Meropol NJ, Giantonio BJ, Diasio RB, Flynn PJ, Catalano P, Hartner L, Rowland KM, Song W, Mulcahy MF, Sinicrope FA, Whitehead RP, Mayer RJ, Petrelli N, O'Dwyer PJ, Hamilton SR, Cella D, Benson AB. Intergroup randomized phase III study of adjuvant FOLFIRI, FOLFOX, or 5-FU/leucovorin for stage II/III rectal cancer: ECOG-ACRIN E3201. Oncologist. 2025 Dec 27;31(1):oyaf416. doi: 10.1093/oncolo/oyaf416.
PubMed 41397917

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 4 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT00068692
Acronym / sponsor ID: NCI-2012-02959
Conditions: Rectal Mucinous Adenocarcinoma, Rectal Signet Ring Cell Adenocarcinoma, Recurrent Rectal Carcinoma, Stage IIA Rectal Cancer AJCC v7, Stage IIB Rectal Cancer AJCC v7, Stage IIC Rectal Cancer AJCC v7
Keywords: rectal cancer, chemotherapy, irinotecan, oxaliplatin
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 225 participants (actual)
Lead sponsor: National Cancer Institute (NCI)US National Institutes of Health
Study start: 15 Oct 2003
Primary completion: 15 Nov 2016 (actual)
Study completion: 15 Nov 2016 (actual)
First posted: 11 Sep 2003 (estimated)
Results: Posted 4 Dec 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

PRIMARY OBJECTIVES:

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:

To determine sphincter preservation, tolerance of treatment and patterns of failure.