Colorectal CancerPhase 2NCT00081289

Neoadjuvant Chemoradiotherapy and Adjuvant Chemotherapy in Treating Patients Who Are Undergoing Surgical Resection for Locally Advanced Rectal Cancer

A Phase 2 study testing Radiation Therapy, Capecitabine 1650 mg/m^2/day and Capecitabine 1200 mg/m^2/day in people with Colorectal Cancer, run by Radiation Therapy Oncology Group at 5 sites 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

RATIONALE: Drugs used in chemotherapy work in 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. Chemoradiotherapy (combining chemotherapy with radiation therapy) before surgery may shrink the tumor so that it can be removed. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Colorectal Cancer
What is being tested?: Radiation Therapy, Capecitabine 1650 mg/m^2/day and Capecitabine 1200 mg/m^2/day
Type of treatment: Pill or oral medicine, Injection or infusion, Surgery or procedure
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 146 participants
Where: 5 sitesUnited States
Study dates: Mar 2004to Dec 2016
Phase: Phase 2
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

Adenocarcinoma of the rectum originating at or below 12 cm from the anal verge without evidence of distant metastases
Patient must be 18 years of age or greater.
Potentially resectable en bloc based upon surgeon evaluation
Clinical stages T3 or T4, based upon endorectal ultrasound, or physical examination (only acceptable for T4 lesions).
Absolute neutrophil count of > 1500 per microliter and platelet count > 100,000 per microliter; aspartate aminotransferase (AST) and alkaline phosphatase < 2.5 X upper limit of normal (ULN), bilirubin < = 1.5 ULN, calculated creatinine clearance > 50 ml/min using Cockcroft-Gault formula:
CrCl male = (140 - age) x (wt. in kg) / (Serum Cr) x 72

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CrCl female = 0.85 x (CrCl male)
Zubrod performance status 0-2
No history of other malignancies within 5 years, except non-melanoma skin cancer, in situ carcinoma of the cervix, or ductal carcinoma in situ of the breast. Previous invasive cancer permitted if disease free at least 5 years.
Signed study-specific informed consent prior to randomization

Who cannot join

Any evidence of distant metastasis
Synchronous primary colon carcinomas, except T1 lesions (full colonoscopy not required for enrollment)
Extension of malignant disease to the anal canal
Prior radiation therapy to the pelvis
Prior chemotherapy for malignancies
Pregnancy or lactation, (exclusion due to potential adverse effects of therapy). Women of childbearing potential with either a positive or no pregnancy test (serum or urine) at baseline. Women/men of childbearing potential not using a reliable and appropriate contraceptive method. (Postmenopausal women must have been amenorrheic for at least 12 months to be considered to be of non-childbearing potential.) Patients will agree to continue contraception for 30 days from the date of the last study drug administration.

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Serious, uncontrolled, concurrent infection(s).
Participation in any investigational drug study within 4 weeks preceding the start of study treatment.
Clinically significant cardiac disease (e.g. congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmias not well controlled with medication) or myocardial infarction within the last 12 months.
Evidence of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant, precluding informed consent, or interfering with compliance of oral drug intake.
Other serious uncontrolled medical conditions that the investigator feels might compromise study participation.
Major surgery within 4 weeks of the study treatment.
Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome.
Known, existing uncontrolled coagulopathy.
No concurrent cimetidine allowed.

Trial locations and contacts

5 sites in 1 country.

City, postcode or hospital

5 sites in 1 country

United States5 sites

Northeast Radiation Oncology Center
Dunmore, Pennsylvania, 18512
Ingalls Cancer Care Center at Ingalls Memorial Hospital
Harvey, Illinois, 60426
Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton
Marlton, New Jersey, 08053
Baptist-South Miami Regional Cancer Program
Miami, Florida, 33176
University of California Davis Cancer Center
Sacramento, California, 95817

Other trials in United States

About this study

Official title: Randomized Phase II Trial Of Neoadjuvant Combined Modality Therapy For Locally Advanced Rectal Cancer

PURPOSE: This randomized phase II trial is studying two different regimens of neoadjuvant chemoradiotherapy and adjuvant chemotherapy and comparing how well they work in treating patients who are undergoing surgical resection for locally advanced rectal cancer.

Read the detailed description

OBJECTIVES:

Evaluate the pathologic complete response rate in patients with locally advanced rectal cancer undergoing surgical resection treated with 2 different regimens of neoadjuvant chemoradiotherapy and adjuvant chemotherapy.
Evaluate the time to treatment failure and patterns of failure in patients treated with these regimens.
Evaluate the incidence of hematologic and non-hematologic grade 3-4 toxicity (preoperatively, postoperatively, and overall) in patients treated with these regimens.
Evaluate the quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to clinical stage of tumor (T3 vs T4). Patients are randomized to 1 of 2 treatment arms.

Quality of life is assessed at baseline, within 1 week after completion of radiotherapy, within 1 week after completion of adjuvant chemotherapy (12 months), and then at 24 months.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Conditions: Colorectal Cancer
Being tested: Radiation Therapy, Capecitabine 1650 mg/m^2/day, Capecitabine 1200 mg/m^2/day, Irinotecan, Oxaliplatin
Keywords: stage III rectal cancer, adenocarcinoma of the rectum, stage II rectal cancer
Medical subject headings: Colorectal Neoplasms, Rectal Neoplasms

What participants receive

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

Radiation TherapyRadiation
Pelvic radiation therapy given once daily 5 days a week for 6 weeks, 45 Gy in 25 fractions + boost of 5.4 Gy in 3 fractions for a total dose of 50.4 Gy.
Capecitabine 1650 mg/m^2/dayDrug
825 mg/m^2 q12 hours (1650 mg/m^2/day) orally 5 days per week during radiotherapy.
Capecitabine 1200 mg/m^2/dayDrug
600 mg/m^2 q12 hours(1200 mg/m^2/day) orally 5 days per week during radiotherapy.
IrinotecanDrug
Also called Irinotecan Hydrochloride
50mg/m^2 IV over 1 hour on days 1, 8, 22, and 29
OxaliplatinDrug
50mg/m^2 IV over 2 hours on days 1, 8, 15, 22, and 29
SurgeryProcedure or surgery
All patients will undergo surgery four to eight weeks following the completion of radiation therapy. The choice of procedure abdominoperineal resection (APR), low anterior resection (LAR), or LAR/coloanal anastomosis is at the discretion of the surgeon.
Folinic AcidDrug
Also called Leucovorin
400 mg/m^2 IV over 2 hours Day 1 (postoperatively) ,every 14 days, for nine 14-day cycles.
FluorouracilDrug
Also called 5-FU
5-fluorouracil bolus 400 mg/m^2 IV push Day 1 (postoperatively), every 14 days, for nine 14-day cycles.
5-fluorouracil infusion 2400 mg/m^2 IV continuous infusion over 46 hours, beginning day 1, every 14 days, for nine 14-day cycles.
OxaliplatinDrug
85 mg/m^2 IV over 2 hours Day 1 (postoperatively), every 14 days, for nine 14-day cycles.

Study groups in NCT00081289
Study group	Role	What they receive
Neoadjuvant chemoradiation with irinotecan	Experimental	Patients receive neoadjuvant therapy comprising 45 Gy (1.8 Gy/fx) + 5.4 Gy boost (1.8 Gy/fx) radiation therapy (RT), oral capecitabine 1200mg/m^2/day 5 days/week during RT, and irinotecan 50 mg/m^2 IV for 1 hour days 1, 8, 22, 29. Surgery 4-8 weeks after RT. Postoperative chemotherapy beginning Day 1 postoperatively for nine 14-day cycles(folinic acid 400 mg/m^2 over 2 hours Day 1; 5-fluorouracil bolus 400 mg/m^2 IV push Day 1 plus 2400 mg/m^2 IV continuous infusion over 46 hours, beginning Day 1; and oxaliplatin 85 mg/m^2 IV over 2 hours Day 1) . Receives: Radiation: Radiation Therapy; Drug: Capecitabine 1200 mg/m^2/day; Drug: Irinotecan; Procedure: Surgery; Drug: Folinic Acid; Drug: Fluorouracil; Drug: Oxaliplatin
Neoadjuvant chemoradiation with oxaliplatin	Experimental	Patients receive neoadjuvant therapy comprising 45 Gy (1.8 Gy/fx) + 5.4 Gy boost (1.8 Gy/fx) radiation therapy (RT), oral capecitabine 1650mg/m^2/day 5 days/week during RT, and oxaliplatin 50 mg/m^2 IV for 2 hours days 1, 8, 15, 22, 29. Surgery 4-8 weeks after RT. Postoperative chemotherapy beginning Day 1 postoperatively for nine 14-day cycles(folinic acid 400 mg/m^2 over 2 hours Day 1; 5-fluorouracil bolus 400 mg/m^2 IV push Day 1 plus 2400 mg/m^2 IV continuous infusion over 46 hours, beginning Day 1; and oxaliplatin 85 mg/m^2 IV over 2 hours Day 1) . Receives: Radiation: Radiation Therapy; Drug: Capecitabine 1650 mg/m^2/day; Drug: Oxaliplatin; Procedure: Surgery; Drug: Folinic Acid; Drug: Fluorouracil

What is being measured

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

Pathologic Complete Response Rate
A pathologic complete response (pCR) was defined as no evidence of residual cancer histologically; disease progression or death before surgery was considered less than pCR (even without surgical specimen). All cases were reviewed by the study's surgical oncology co-chair for the determination of pCR.
Each arm was first analyzed alone. If the arm had 9 or more pCRs in 48 evaluable pts, then the null hypothesis (H0) of 10% pCR rate would be rejected in favor of the alternative hypothesis of 25%, providing 90% power with a two-sided 10% type I error rate. If both arms reject H0, then statistical selection theory would be used to choose the arm for further study in a phase III trial. If only one arm has acceptable pCR rate, then that arm would be pursued in a phase III trial.
Measured: After protocol surgery, approximately 10-16 weeks from randomization based on surgery occurring 4-8 weeks after chemoradiation

Secondary outcomes (18)

Survival Rate at 4 Years
Survival time is defined as time from registration/randomization to the date of death from any cause or last known follow-up (censored). Survival rates are estimated by the Kaplan-Meier method.
Measured: From randomization to four years
Local-regional Failure Rate at 4 Years
Local-regional failure is defined as any of the following: no clinical complete response (cCR) in the primary site and/or nodes at any time after treatment completion (persistence), recurrence and/or progression in the primary site and/or nodes after cCR, and nonprotocol surgery to the primary site after cCR. Time to local-regional failure is defined as time from randomization to date of failure, last known follow-up (censored), or death without local-regional failure (competing risk). Local-regional failure rates are estimated by the cumulative incidence method.
Measured: From randomization to four years
Distant Failure Rate at 4 Years
Time to distant failure is defined as time from randomization to date of the appearance of distant metastases, last known follow-up (censored), or death without distant failure (competing risk). Distant failure rates are estimated by the cumulative incidence method.
Measured: From randomization to four years
Second Primary Rate at 4 Years
Time to second primary is defined as time from randomization to date of the appearance of a second primary cancer, last known follow-up (censored), or death without second primary (competing risk). Second primary rates are estimated by the cumulative incidence method.
Measured: From randomization to four years
Disease-free Survival Rate at 4 Years
Disease-free survival time is defined as time from randomization to date of local-regional failure, the appearance of distant metastases, the appearance of a second primary failure, or date of death from any cause/ Disease-free survival rates are estimated by the Kaplan-Meier method. Patients last known to be alive without failure are censored at the date of last contact.
Measured: From randomization to four years
Number of Participants With Grade 3+ Treatment-related Adverse Events
Highest grade adverse event per subject were counted. Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE.
Measured: From start of treatment to end of follow-up. Maximum follow-up is 5.2 years.
Number of Participants With Grade 3+ Treatment-related Adverse Events Preoperatively
Highest grade adverse event per subject were counted. Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE.
Measured: From start of treatment to surgery, approximately 10-16 weeks from randomization based on surgery occurring 4-8 weeks after chemoradiation. If no surgery, then <= 90 days from start of treatment.
Number of Participants With Grade 3+ Treatment-related Adverse Events Postoperatively
Highest grade adverse event per subject were counted. Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE.
Measured: From post-surgery to before chemotherapy (CT), or within 60 days of surgery if no postoperative CT. Approximately 10-16 weeks to 14-22 weeks from randomization based on CT starting 4-6 weeks after surgery.
Tumor Marker Evaluation Using Preoperative Tissue Biopsy Specimens and Surgically Resected Tissue Specimens
Measured: End of study
Change From Baseline in QLQ-C30 Global Health Status Score at Completion of Chemoradiation
Global Health Status is calculated from two questions on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ]-C30. The question responses range from 1 "very poor" to 7 "excellent" such that a higher response indicates better quality of life (QOL). The mean of these responses is linearly transformed to a range of 0 (worst) to 100 (best). Change from baseline is calculated as the time point value - baseline value and a decrease from baseline indicates decline in quality of life. A positive number indicates improvement in QOL.
Measured: Baseline and completion of chemoradiation, approximately 6-8 weeks from randomization
Change From Baseline in QLQ-C30 Global Health Status Score at Completion of Post-operative Chemotherapy
Global Health Status is calculated from two questions on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ]-C30. The question responses range from 1 "very poor" to 7 "excellent" such that a higher response indicates better quality of life (QOL). The mean of these responses is linearly transformed to a range of 0 (worst) to 100 (best). Change from baseline is calculated as the time point value - baseline value and a decrease from baseline indicates decline in quality of life. A positive number indicates improvement in QOL.
Measured: Baseline and completion of post-operative chemotherapy approximately 32 to 40 weeks from randomization based on 18 weeks of post-operative chemotherapy
Change From Baseline in QLQ-C30 Global Health Status Score at Two Years
Global Health Status is calculated from two questions on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ]-C30. The question responses range from 1 "very poor" to 7 "excellent" such that a higher response indicates better quality of life (QOL). The mean of these responses is linearly transformed to a range of 0 (worst) to 100 (best). Change from baseline is calculated as the time point value - baseline value and a decrease from baseline indicates decline in quality of life. A negative number indicates improvement in symptoms.
Measured: Baseline and two years
Change From Baseline in EORTC QLQ-CR38 Gastro-intestinal Symptom Score at Completion of Chemoradiation
The gastro-intestinal (GI) symptom score is calculated from five symptom questions on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ]-CR38. The question responses range from 1 (not at all) to 4 (very much) such that a higher response indicates worse symptoms. The mean of these responses is linearly transformed to a range of 0 (best) to 100 (worst). Change from baseline is calculated as the time point value - baseline value and a decrease from baseline indicates improvement in symptoms. A negative number indicates improvement in symptoms.
Measured: Baseline and completion of chemoradiation approximately 6-8 weeks from randomization
Change From Baseline in EORTC QLQ-CR38 Gastro-intestinal Symptom Score at Completion of Post-operative Chemotherapy
The gastro-intestinal (GI) symptom score is calculated from five symptom questions on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ]-CR38. The question responses range from 1 (not at all) to 4 (very much) such that a higher response indicates worse symptoms. The mean of these responses is linearly transformed to a range of 0 (best) to 100 (worst). Change from baseline is calculated as the time point value - baseline value and a decrease from baseline indicates improvement in symptoms. A negative number indicates improvement in symptoms.
Measured: Baseline and completion of post-operative chemotherapy approximately 32 to 40 weeks from randomization based on 18 weeks of post-operative chemotherapy
Change From Baseline in EORTC QLQ-CR38 Gastro-intestinal Symptom Score at Two Years
The gastro-intestinal (GI) symptom score is calculated from five symptom questions on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ]-CR38. The question responses range from 1 (not at all) to 4 (very much) such that a higher response indicates worse symptoms. The mean of these responses is linearly transformed to a range of 0 (best) to 100 (worst). Change from baseline is calculated as the time point value - baseline value and a decrease from baseline indicates improvement in symptoms. A negative number indicates improvement in symptoms.
Measured: Baseline and two years
Change From Baseline in EORTC QLQ-CR38 Defecation Symptom Score at Completion of Chemoradiation
The defecation symptom score is calculated from seven symptom questions on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ]-CR38. The question responses range from 1 "not at all" to 4 "very much" such that a higher response indicates worse symptoms. The mean of these responses is linearly transformed to a range of 0 (best) to 100 (worst). Change from baseline is calculated as the time point value - baseline value and a decrease from baseline indicates improvement in symptoms. A negative number indicates improvement in symptoms.
Measured: Baseline and completion of chemoradiation, approximately 6-8 weeks from randomization
Change From Baseline in EORTC QLQ-CR38 Defecation Symptom Score at Post-operative Chemotherapy
The defecation symptom score is calculated from seven symptom questions on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ]-CR38. The question responses range from 1 "not at all" to 4 "very much" such that a higher response indicates worse symptoms. The mean of these responses is linearly transformed to a range of 0 (best) to 100 (worst). Change from baseline is calculated as the time point value - baseline value and a decrease from baseline indicates improvement in symptoms. A negative number indicates improvement in symptoms.
Measured: Baseline and completion of post-operative chemotherapy, approximately 32 to 40 weeks from randomization based on 18 weeks of post-operative chemotherapy
Change From Baseline in EORTC QLQ-CR38 Defecation Symptom Score at Two Years
The defecation symptom score is calculated from seven symptom questions on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ]-CR38. The question responses range from 1 "not at all" to 4 "very much" such that a higher response indicates worse symptoms. The mean of these responses is linearly transformed to a range of 0 (best) to 100 (worst). Change from baseline is calculated as the time point value - baseline value and a decrease from baseline indicates improvement in symptoms. A negative number indicates improvement in symptoms.
Measured: Baseline and two years

Timeline

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

Mar 2004Dec 2016

First posted8 Apr 2004 (estimated)
Study startMar 2004
Primary completionMay 2011
Study completionDec 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 (2)Papers the sponsor has linked to this study.
Other trials for Colorectal CancerStudies of the same condition, open and under way.
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 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 146 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00081289
Sponsor's protocol ID: RTOG-0247
Other IDs: CDR0000350136
Status last verified: Feb 2020
First submitted: 7 Apr 2004
Last updated: 27 Feb 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Wong SJ, Winter K, Meropol NJ, Anne PR, Kachnic L, Rashid A, Watson JC, Mitchell E, Pollock J, Lee RJ, Haddock M, Erickson BA, Willett CG. Radiation Therapy Oncology Group 0247: a randomized Phase II study of neoadjuvant capecitabine and irinotecan or capecitabine and oxaliplatin with concurrent radiotherapy for patients with locally advanced rectal cancer. Int J Radiat Oncol Biol Phys. 2012 Mar 15;82(4):1367-75. doi: 10.1016/j.ijrobp.2011.05.027. Epub 2011 Jul 19.
PubMed 21775070
Wong SJ, Moughan J, Meropol NJ, et al.: Efficacy endpoints of RTOG 0247: A randomized phase II study of neoadjuvant capecitabine (C) and irinotecan (I) or C and oxaliplatin (O) with concurrent radiation therapy (RT) for locally advanced rectal cancer. [Abstract] J Clin Oncol 29 (Suppl 15): A-3517, 2011.

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 27 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Randomized Phase II Trial Of Neoadjuvant Combined Modality Therapy For Locally Advanced Rectal Cancer
ClinicalTrials.gov ID: NCT00081289
Acronym / sponsor ID: RTOG-0247
Conditions: Colorectal Cancer
Keywords: stage III rectal cancer, adenocarcinoma of the rectum, stage II rectal cancer
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 146 participants (actual)
Lead sponsor: Radiation Therapy Oncology GroupResearch network
Collaborators: National Cancer Institute (NCI)
Study start: Mar 2004
Primary completion: May 2011 (actual)
Study completion: Dec 2016 (actual)
First posted: 8 Apr 2004 (estimated)
Results: Posted 25 Nov 2013

Clinical summary

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

Detailed description

OBJECTIVES:

Evaluate the pathologic complete response rate in patients with locally advanced rectal cancer undergoing surgical resection treated with 2 different regimens of neoadjuvant chemoradiotherapy and adjuvant chemotherapy.
Evaluate the time to treatment failure and patterns of failure in patients treated with these regimens.
Evaluate the incidence of hematologic and non-hematologic grade 3-4 toxicity (preoperatively, postoperatively, and overall) in patients treated with these regimens.
Evaluate the quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to clinical stage of tumor (T3 vs T4). Patients are randomized to 1 of 2 treatment arms.

Quality of life is assessed at baseline, within 1 week after completion of radiotherapy, within 1 week after completion of adjuvant chemotherapy (12 months), and then at 24 months.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Neoadjuvant chemoradiation with irinotecan	Experimental	Radiation: Radiation Therapy, Drug: Capecitabine 1200 mg/m^2/day, Drug: Irinotecan, Procedure: Surgery, Drug: Folinic Acid, Drug: Fluorouracil, Drug: OxaliplatinPatients receive neoadjuvant therapy comprising 45 Gy (1.8 Gy/fx) + 5.4 Gy boost (1.8 Gy/fx) radiation therapy (RT), oral capecitabine 1200mg/m^2/day 5 days/week during RT, and irinotecan 50 mg/m^2 IV for 1 hour days 1, 8, 22, 29. Surgery 4-8 weeks after RT. Postoperative chemotherapy beginning Day 1 postoperatively for nine 14-day cycles(folinic acid 400 mg/m^2 over 2 hours Day 1; 5-fluorouracil bolus 400 mg/m^2 IV push Day 1 plus 2400 mg/m^2 IV continuous infusion over 46 hours, beginning Day 1; and oxaliplatin 85 mg/m^2 IV over 2 hours Day 1) .
Neoadjuvant chemoradiation with oxaliplatin	Experimental	Radiation: Radiation Therapy, Drug: Capecitabine 1650 mg/m^2/day, Drug: Oxaliplatin, Procedure: Surgery, Drug: Folinic Acid, Drug: FluorouracilPatients receive neoadjuvant therapy comprising 45 Gy (1.8 Gy/fx) + 5.4 Gy boost (1.8 Gy/fx) radiation therapy (RT), oral capecitabine 1650mg/m^2/day 5 days/week during RT, and oxaliplatin 50 mg/m^2 IV for 2 hours days 1, 8, 15, 22, 29. Surgery 4-8 weeks after RT. Postoperative chemotherapy beginning Day 1 postoperatively for nine 14-day cycles(folinic acid 400 mg/m^2 over 2 hours Day 1; 5-fluorouracil bolus 400 mg/m^2 IV push Day 1 plus 2400 mg/m^2 IV continuous infusion over 46 hours, beginning Day 1; and oxaliplatin 85 mg/m^2 IV over 2 hours Day 1) .

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (10 listed)

Adenocarcinoma of the rectum originating at or below 12 cm from the anal verge without evidence of distant metastases
Patient must be 18 years of age or greater.
Potentially resectable en bloc based upon surgeon evaluation
Clinical stages T3 or T4, based upon endorectal ultrasound, or physical examination (only acceptable for T4 lesions).
Absolute neutrophil count of > 1500 per microliter and platelet count > 100,000 per microliter; aspartate aminotransferase (AST) and alkaline phosphatase < 2.5 X upper limit of normal (ULN), bilirubin < = 1.5 ULN, calculated creatinine clearance > 50 ml/min using Cockcroft-Gault formula:

Key exclusion criteria (15 listed)

Any evidence of distant metastasis
Synchronous primary colon carcinomas, except T1 lesions (full colonoscopy not required for enrollment)
Extension of malignant disease to the anal canal
Prior radiation therapy to the pelvis
Prior chemotherapy for malignancies

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Radiation TherapyPelvic radiation therapy given once daily 5 days a week for 6 weeks, 45 Gy in 25 fractions + boost of 5.4 Gy in 3 fractions for a total dose of 50.4 Gy.	Radiation	Neoadjuvant chemoradiation with irinotecan, Neoadjuvant chemoradiation with oxaliplatin
Capecitabine 1650 mg/m^2/day825 mg/m^2 q12 hours (1650 mg/m^2/day) orally 5 days per week during radiotherapy.	Drug	Neoadjuvant chemoradiation with oxaliplatin
Capecitabine 1200 mg/m^2/day600 mg/m^2 q12 hours(1200 mg/m^2/day) orally 5 days per week during radiotherapy.	Drug	Neoadjuvant chemoradiation with irinotecan
IrinotecanAlso: Irinotecan Hydrochloride50mg/m^2 IV over 1 hour on days 1, 8, 22, and 29	Drug	Neoadjuvant chemoradiation with irinotecan
Oxaliplatin50mg/m^2 IV over 2 hours on days 1, 8, 15, 22, and 29	Drug	Neoadjuvant chemoradiation with oxaliplatin
SurgeryAll patients will undergo surgery four to eight weeks following the completion of radiation therapy. The choice of procedure abdominoperineal resection (APR), low anterior resection (LAR), or LAR/coloanal anastomosis is at the discretion of the surgeon.	Procedure or surgery	Neoadjuvant chemoradiation with irinotecan, Neoadjuvant chemoradiation with oxaliplatin
Folinic AcidAlso: Leucovorin400 mg/m^2 IV over 2 hours Day 1 (postoperatively) ,every 14 days, for nine 14-day cycles.	Drug	Neoadjuvant chemoradiation with irinotecan, Neoadjuvant chemoradiation with oxaliplatin
FluorouracilAlso: 5-FU5-fluorouracil bolus 400 mg/m^2 IV push Day 1 (postoperatively), every 14 days, for nine 14-day cycles. 5-fluorouracil infusion 2400 mg/m^2 IV continuous infusion over 46 hours, beginning day 1, every 14 days, for nine 14-day cycles.	Drug	Neoadjuvant chemoradiation with irinotecan, Neoadjuvant chemoradiation with oxaliplatin
Oxaliplatin85 mg/m^2 IV over 2 hours Day 1 (postoperatively), every 14 days, for nine 14-day cycles.	Drug	Neoadjuvant chemoradiation with irinotecan, Neoadjuvant chemoradiation with oxaliplatin

Primary outcome

Pathologic Complete Response Rate
Time frame: After protocol surgery, approximately 10-16 weeks from randomization based on surgery occurring 4-8 weeks after chemoradiation
A pathologic complete response (pCR) was defined as no evidence of residual cancer histologically; disease progression or death before surgery was considered less than pCR (even without surgical specimen). All cases were reviewed by the study's surgical oncology co-chair for the determination of pCR. Each arm was first analyzed alone. If the arm had 9 or more pCRs in 48 evaluable pts, then the null hypothesis (H0) of 10% pCR rate would be rejected in favor of the alternative hypothesis of 25%, providing 90% power with a two-sided 10% type I error rate. If both arms reject H0, then statistical selection theory would be used to choose the arm for further study in a phase III trial. If only one arm has acceptable pCR rate, then that arm would be pursued in a phase III trial.

18 secondary outcomes

Survival Rate at 4 Years
Time frame: From randomization to four years
Local-regional Failure Rate at 4 Years
Time frame: From randomization to four years
Distant Failure Rate at 4 Years
Time frame: From randomization to four years
Second Primary Rate at 4 Years
Time frame: From randomization to four years
Disease-free Survival Rate at 4 Years
Time frame: From randomization to four years
Number of Participants With Grade 3+ Treatment-related Adverse Events
Time frame: From start of treatment to end of follow-up. Maximum follow-up is 5.2 years.
Number of Participants With Grade 3+ Treatment-related Adverse Events Preoperatively
Time frame: From start of treatment to surgery, approximately 10-16 weeks from randomization based on surgery occurring 4-8 weeks after chemoradiation. If no surgery, then <= 90 days from start of treatment.
Number of Participants With Grade 3+ Treatment-related Adverse Events Postoperatively
Time frame: From post-surgery to before chemotherapy (CT), or within 60 days of surgery if no postoperative CT. Approximately 10-16 weeks to 14-22 weeks from randomization based on CT starting 4-6 weeks after surgery.
Tumor Marker Evaluation Using Preoperative Tissue Biopsy Specimens and Surgically Resected Tissue Specimens
Time frame: End of study
Change From Baseline in QLQ-C30 Global Health Status Score at Completion of Chemoradiation
Time frame: Baseline and completion of chemoradiation, approximately 6-8 weeks from randomization
Change From Baseline in QLQ-C30 Global Health Status Score at Completion of Post-operative Chemotherapy
Time frame: Baseline and completion of post-operative chemotherapy approximately 32 to 40 weeks from randomization based on 18 weeks of post-operative chemotherapy
Change From Baseline in QLQ-C30 Global Health Status Score at Two Years
Time frame: Baseline and two years
Change From Baseline in EORTC QLQ-CR38 Gastro-intestinal Symptom Score at Completion of Chemoradiation
Time frame: Baseline and completion of chemoradiation approximately 6-8 weeks from randomization
Change From Baseline in EORTC QLQ-CR38 Gastro-intestinal Symptom Score at Completion of Post-operative Chemotherapy
Time frame: Baseline and completion of post-operative chemotherapy approximately 32 to 40 weeks from randomization based on 18 weeks of post-operative chemotherapy
Change From Baseline in EORTC QLQ-CR38 Gastro-intestinal Symptom Score at Two Years
Time frame: Baseline and two years
Change From Baseline in EORTC QLQ-CR38 Defecation Symptom Score at Completion of Chemoradiation
Time frame: Baseline and completion of chemoradiation, approximately 6-8 weeks from randomization
Change From Baseline in EORTC QLQ-CR38 Defecation Symptom Score at Post-operative Chemotherapy
Time frame: Baseline and completion of post-operative chemotherapy, approximately 32 to 40 weeks from randomization based on 18 weeks of post-operative chemotherapy
Change From Baseline in EORTC QLQ-CR38 Defecation Symptom Score at Two Years
Time frame: Baseline and two years

Results and safety

Results posted to the registry on 25 Nov 2013, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Neoadjuvant Chemoradiation With Irinotecan	73	52
Neoadjuvant Chemoradiation With Oxaliplatin	73	52

Primary outcome: Pathologic Complete Response Rate

Time frame: After protocol surgery, approximately 10-16 weeks from randomization based on surgery occurring 4-8 weeks after chemoradiation. Number (95% Confidence Interval). Unit: percentage of participants

Measure	Neoadjuvant Chemoradiation With Irinotecan n = 48	Neoadjuvant Chemoradiation With Oxaliplatin n = 48
Value	10.4 (3.5 to 22.7)	20.8 (10.5 to 35.0)

Population analysed: For each arm the first 48 eligible enrolled after the protocol amendment.

18 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Neoadjuvant Chemoradiation With Irinotecan	37 of 70 (52.9%)	70 of 70 (100%)	Not reported
Neoadjuvant Chemoradiation With Oxaliplatin	36 of 68 (52.9%)	67 of 68 (98.5%)	Not reported

Limitations and caveats (from the sponsor): Due to excessive GI adverse events in the first 35 patients, chemotherapy dosage was modified and the protocol was amended (treatment descriptions reflect the revision). Therefore the first 35 patients are not included in outcome measure results.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 27 Feb 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 21775070Wong SJ, Winter K, Meropol NJ, Anne PR, Kachnic L, Rashid A, Watson JC, Mitchell E, Pollock J, Lee RJ, Haddock M, Erickson BA, Willett CG. Radiation Therapy Oncology Group 0247: a randomized Phase II study of neoadjuvant capecitabine and irinotecan or capecitabine and oxaliplatin with concurrent radiotherapy for patients with locally advanced rectal cancer. Int J Radiat Oncol Biol Phys. 2012 Mar 15;82(4):1367-75. doi: 10.1016/j.ijrobp.2011.05.027. Epub 2011 Jul 19.
Results publicationWong SJ, Moughan J, Meropol NJ, et al.: Efficacy endpoints of RTOG 0247: A randomized phase II study of neoadjuvant capecitabine (C) and irinotecan (I) or C and oxaliplatin (O) with concurrent radiation therapy (RT) for locally advanced rectal cancer. [Abstract] J Clin Oncol 29 (Suppl 15): A-3517, 2011.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Neal J. Meropol, MD principal investigator

Fox Chase Cancer Center

5 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 Nov 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pathologic Complete Response Rate (time frame: After protocol surgery, approximately 10-16 weeks from randomization based on surgery occurring 4-8 weeks after chemoradiation). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00081289, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Feb 2020.