Colorectal CancerPhase 3NCT00058474
Radiation Therapy and Either Capecitabine or Fluorouracil With or Without Oxaliplatin Before Surgery in Treating Patients With Resectable Rectal Cancer
A Phase 3 study testing capecitabine, fluorouracil and oxaliplatin in people with Colorectal Cancer, run by NSABP Foundation Inc.
Trial summary
RATIONALE: Drugs used in chemotherapy, such as capecitabine, fluorouracil, and oxaliplatin 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. 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?
- capecitabine, fluorouracil and oxaliplatin
- 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
- 1,608 participants
- Where
- No sites listed yet
- Study dates
- Jul 2004to May 2016
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 consent to participate in the study and must have signed and dated an IRB-approved consent form conforming to federal and institutional guidelines.
- Patients must be > 18 years of age.
- Patients must have a life expectancy of 5 years, excluding their diagnosis of cancer (as determined by the investigator), and must have an Eastern Cooperative Oncology Group (ECOG) (Zubrod) performance status of 0 or 1.
- Patients must have a diagnosis of adenocarcinoma of the rectum obtained by a biopsy technique which leaves the major portion of the tumor intact.
- The interval between the initial diagnosis of rectal adenocarcinoma and randomization must be no more than 42 days.
- Prior to randomization, the investigator must specify the intent for sphincter saving or non-sphincter saving surgery.
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- The tumor must be either palpable by digital rectal exam or be accessible via a proctoscope or sigmoidoscope.
- Distal border of the tumor must be located < 12 cm from the anal verge.
- The tumor must be considered by the surgeon to be amenable to curative resection. (Note that curative resection can include pelvic exenteration.)
- The tumor must be clinically Stage II (T3-4 N0 with N0 being defined as all imaged lymph nodes are < 1.0 cm) or Stage III (T1-4 N1-2 with the definition of a clinically positive node being any node > 1.0 cm). Stage of the primary tumor may be determined by ultrasound or Magnetic Resonance Imaging (MRI). Computed Tomography (CT) scan is acceptable provided there is evidence of T4 and/or N1-2 disease.
- At the time of randomization, all patients must have had the following within the previous 42 days: history and physical examination; if technically feasible, a complete colonoscopic examination; if not feasible, a proctoscopic or sigmoidoscopic exam; clinical staging of the tumor; CT or MRI of the abdomen and pelvis (combined PET/CT may be substituted), and a chest x-ray (PA and lateral) or CT scan of the chest to exclude patients with metastatic disease.
- At the time of randomization: Absolute neutrophil count (ANC) must be > 1,200/mm3; Platelet count must be > 100,000/mm3; There must be evidence of adequate hepatic function as follows: total bilirubin must be < 1.5 x the upper limit of normal (ULN) for the lab; and alkaline phosphatase must be < 2.5 x Upper Limit of Normal (ULN) for the lab; and the Aspartate Amino Transferase (AST) must be < 2.5 x ULN for the lab; and If AST is > ULN, serologic testing for Hepatitis B and C must be performed and results must be negative; Calculated creatinine clearance must be > 50 mL/min.
- Patients with prior malignancies, including invasive colon cancer, are eligible if they have been disease-free for > 5 years and are deemed by their physician to be at low risk for recurrence. Patients with squamous or basal cell carcinoma of the skin, melanoma in situ, carcinoma in situ of the cervix, or carcinoma in situ of the colon or rectum that have been effectively treated are eligible, even if these conditions were diagnosed within 5 years prior to randomization.
Who cannot join
- Findings of metastatic disease.
- On imaging, clear indication of involvement of the pelvic side wall(s).
- Rectal cancers other than adenocarcinoma, i.e., sarcoma, lymphoma, carcinoid, squamous cell carcinoma, cloacogenic carcinoma, etc.
- History of invasive rectal malignancy, regardless of disease-free interval.
- Pregnancy or lactation at the time of proposed randomization. Eligible patients of reproductive potential (both sexes) must agree to use adequate contraceptive methods.
- Any therapy for this cancer prior to randomization.
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- Synchronous colon cancer.
- History of viral hepatitis or other chronic liver disease.
- Nonmalignant systemic disease (cardiovascular, renal, hepatic, etc.) that would preclude the patient from receiving any chemotherapy treatment option or would prevent required follow-up. Specifically excluded are patients with active ischemic heart disease (class III* or class IV myocardial disease as described by the New York Heart Association), a recent history (within 6 months) of myocardial infarction, or symptomatic arrhythmia at the time of randomization. *Class III: Patients with cardiac disease resulting in marked limitation of physical activity. Such patients are comfortable at rest. Less than ordinary physical activity that causes fatigue, palpitation, dyspnea, or anginal pain. Class IV: Patients with cardiac disease resulting in inability to perform any physical activity without discomfort. Symptoms of cardiac insufficiency or anginal syndrome may be present even at rest.
- Patients who, in the opinion of the investigator, have uncontrolled hypertension.
- Active inflammatory bowel disease (i.e., patients requiring current medical interventions or who are symptomatic).
- Prior pelvic radiation therapy for any reason.
- Known hypersensitivity to 5-fluorouracil, capecitabine, or oxaliplatin.
- Clinically significant peripheral neuropathy at the time of randomization (defined in the NCI Common Terminology Criteria for Adverse Events Version 3.0 [CTCAE v3.0] as grade 2 or greater neurosensory or neuromotor toxicity).
- Existing uncontrolled coagulopathy.
- Inability to take oral medications.
- Participation in any investigational drug study within 4 weeks prior to randomization.
- Psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements.
About this study
Official title: A Clinical Trial Comparing Preoperative Radiation Therapy And Capecitabine With or Without Oxaliplatin With Preoperative Radiation Therapy And Continuous Intravenous Infusion Of 5-Fluorouracil With or Without Oxaliplatin In The Treatment Of Patients With Operable Carcinoma Of The Rectum
RATIONALE: Drugs used in chemotherapy, such as capecitabine, fluorouracil, and oxaliplatin 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.
PURPOSE: This randomized phase III trial is studying radiation therapy and either capecitabine or fluorouracil with or without oxaliplatin and comparing them to see how well they work when given before surgery in treating patients with resectable rectal cancer. It is not yet known whether radiation therapy and either capecitabine or fluorouracil is more effective with or without oxaliplatin in treating rectal cancer.
Read the detailed description
OBJECTIVES:
Primary
- Compare the rate of local-regional relapse in patients with resectable rectal cancer treated with chemoradiotherapy comprising radiation therapy and either capecitabine or fluorouracil with or without oxaliplatin.
Secondary
- Compare the rate of clinical complete response in patients treated with these regimens.
- Compare the rate of pathologic complete response in patients treated with these regimens.
- Determine the increase in the number of patients who are able to undergo sphincter-saving surgery after treatment with these regimens.
- Correlate genetic patterns and the presence or absence of specific tissue biomarkers with response and prognosis in patients treated with these regimens.
- Compare preoperative quality of life (QOL) of patients treated with oral capecitabine versus continuous infusion with fluorouracil.
- Determine the impact of oxaliplatin on neurotoxicity in patients treated with these regimens.
- Compare the toxic effects of these regimens in these patients.
- Compare the convenience of care in patients treated with these regimens.
- Determine the impact of the type of surgical management on QOL at 1 and 5 years postoperatively in these patients.
- Describe the long-term impact of cancer treatment on symptoms (e.g., vitality and neurotoxicity) and QOL at 5 years after randomization (5-year follow-up visit).
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center, gender, clinical tumor stage (stage II vs stage III), and surgical intent (sphincter saving vs non-sphincter saving). Patients are randomized to 1 of 4 treatment arms.
- Arm 1: Patients receive fluorouracil IV continuously and undergo radiotherapy once daily 5 days a week for 5-6 weeks.
- Arm 2: Patients receive fluorouracil and undergo radiotherapy as in arm 1. Patients also receive oxaliplatin IV over 1 hour once weekly for 5 weeks.
- Arm 3: Patients receive oral capecitabine twice daily and undergo radiotherapy once daily 5 days a week for 5-6 weeks.
- Arm 4: Patients receive capecitabine and undergo radiotherapy as in arm 3. Patients also receive oxaliplatin as in arm 2.
Within 6-8 weeks after the completion of chemoradiotherapy, patients with responding or stable disease undergo surgery. Patients with progressive disease are treated at the discretion of the investigator and continue to be followed.
Quality of life is assessed at baseline, at completion of chemoradiotherapy, and at 1 and 5 years after surgery.
After completion of study treatment, patients are followed every 6 months for 5 years.
PROJECTED ACCRUAL: A total of 1,606 patients will be accrued for this study within 4 years.
- Conditions
- Colorectal Cancer
- Being tested
- capecitabine, fluorouracil, oxaliplatin, radiation therapy
- Keywords
- stage II rectal cancer, stage III rectal cancer, adenocarcinoma of the rectum
- 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.
capecitabineDrug
825 mg/m2 oral daily 5 days a week on days of planned RT
fluorouracilDrug
Also called 5-FU
225 mg/m2 IV daily continuous infusion
oxaliplatinDrug
50 mg/m2 IV 5 days a week on days of planned RT
radiation therapyRadiation
Also called RT
Given 5 days a week for 5-6 weeks
| Study group | Role | What they receive |
|---|---|---|
| Arm 1: 5-FU + RT | Active comparator | Patients receive fluorouracil IV continuously and undergo radiation therapy (RT) once daily 5 days a week for 5-6 weeks. Receives: Drug: fluorouracil; Radiation: radiation therapy |
| Arm 2: 5-FU + RT + Oxaliplatin | Experimental | Patients receive fluorouracil and undergo RT as in arm 1. Patients also receive oxaliplatin IV over 1 hour once weekly for 5 weeks. Receives: Drug: fluorouracil; Drug: oxaliplatin; Radiation: radiation therapy |
| Arm 3: Capecitabine + RT | Experimental | Patients receive oral capecitabine twice daily and undergo RT once daily 5 days a week for 5-6 weeks. Receives: Drug: capecitabine; Radiation: radiation therapy |
| Arm 4: Capecitabine + RT + Oxaliplatin | Experimental | Patients receive capecitabine and undergo RT as in arm 3. Patients also receive oxaliplatin as in arm 2. Receives: Drug: capecitabine; Drug: oxaliplatin; Radiation: radiation therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Loco-regional disease control as assessed by evidence of tumor at 3 years
Measured: Time from randomization to first local recurrence up to 3 years
Secondary outcomes (11)
Clinical complete response as assessed by digital rectal exam and sigmoidoscopy or proctoscopy at time of definitive analysis
Measured: Prior to surgery approximately 6 weeks
Pathologic complete response as assessed by gross and microscopic exam of surgical specimens at time of definitive analysis
Measured: At the time of surgery approximately 6 weeks
Sphincter-saving surgery at time of definitive analysis
Measured: At the time of surgery approximately 6 weeks
Survival as measured by deaths from any cause at time of definitive analysis
Measured: From time of randomization through 5 years
Disease-free survival as assessed by recurrence, second primary cancer, or death from any cause at time of definitive analysis
Measured: From time of randomization through 5 years
Tissue biomarkers as assessed by analysis of tumor tissue using current biotechnology after definitive analysis
Measured: At the time of surgery approximately 6 weeks
Quality of life as assessed by FACT-C trial outcome index and EORTC CR38 after definitive analysis
Measured: Assessed prior to therapy and at approximately 5 weeks, 15 months, 5 years
Neurotoxicity as assessed by FACT-NTX scale after definitive analysis
Measured: Assessed prior to therapy and at approximately 5 weeks, 15 months, 5 years
Symptoms as assessed by fluoropyrimidine symptom scale adapted from SWOG after definitive analysis
Measured: Assessed prior to therapy and at approximately 5 weeks, 15 months
Vitality as assessed by SF-36 vitality scale after definitive analysis
Measured: Assessed prior to therapy and at approximately 5 weeks, 15 months, 5 years
Convenience of care as assessed by NSABP C-06 convenience of care scale adapted from ECOG after definitive analysis
Measured: Assessed prior to therapy and at approximately 5 weeks, 15 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Apr 2003 (estimated)
- Study startJul 2004
- Primary completionAug 2013
- Study completionMay 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1,608 participants (actual)
Sponsor and investigators
- Lead sponsor
- NSABP Foundation Inc
- Sponsor type
- Research network
- Collaborators
- National Cancer Institute (NCI), Cancer and Leukemia Group B
- Responsible party
- Sponsor
- Investigators
- Norman Wolmark, MD, Principal investigator, NSABP Foundation Inc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00058474
- Sponsor's protocol ID
- NSABP R-04
- Other IDs
- NSABP-R-04, CALGB-NSABP-R-04
- Status last verified
- Mar 2016
- First submitted
- 7 Apr 2003
- Last updated
- 23 Mar 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Ganz PA, Lopa SH, Yothers G, et al.: Comparative effectiveness of sphincter-sparing surgery (SSS) versus abdomino-perineal resection (APR) in rectal cancer: patient-reported outcomes (PROs) from NSABP R-04. [Abstract] J Clin Oncol 30 (Suppl 15): A-3545, 2012.
Roh MS, Yothers GA, O'Connell MJ, et al.: The impact of capecitabine and oxaliplatin in the preoperative multimodality treatment in patients with carcinoma of the rectum: NSABP R-04. [Abstract] J Clin Oncol 29 (Suppl 15): A-3503, 2011.
O'Connell MJ, Colangelo LH, Beart RW, Petrelli NJ, Allegra CJ, Sharif S, Pitot HC, Shields AF, Landry JC, Ryan DP, Parda DS, Mohiuddin M, Arora A, Evans LS, Bahary N, Soori GS, Eakle J, Robertson JM, Moore DF Jr, Mullane MR, Marchello BT, Ward PJ, Wozniak TF, Roh MS, Yothers G, Wolmark N. Capecitabine and oxaliplatin in the preoperative multimodality treatment of rectal cancer: surgical end points from National Surgical Adjuvant Breast and Bowel Project trial R-04. J Clin Oncol. 2014 Jun 20;32(18):1927-34. doi: 10.1200/JCO.2013.53.7753. Epub 2014 May 5.
PubMed 24799484Russell MM, Ganz PA, Lopa S, Yothers G, Ko CY, Arora A, Atkins JN, Bahary N, Soori GS, Robertson JM, Eakle J, Marchello BT, Wozniak TF, Beart RW Jr, Wolmark N. Comparative effectiveness of sphincter-sparing surgery versus abdominoperineal resection in rectal cancer: patient-reported outcomes in National Surgical Adjuvant Breast and Bowel Project randomized trial R-04. Ann Surg. 2015 Jan;261(1):144-8. doi: 10.1097/SLA.0000000000000594.
PubMed 24670844Peipert JD, Roydhouse J, Tighiouart M, Henry NL, Kim S, Hays RD, Rogatko A, Yothers G, Ganz PA. Overall side effect assessment of oxaliplatin toxicity in rectal cancer patients in NRG oncology/NSABP R04. Qual Life Res. 2024 Nov;33(11):3069-3079. doi: 10.1007/s11136-024-03746-5. Epub 2024 Jul 30.
PubMed 39080091Ganz PA, Hays RD, Spritzer KL, Rogatko A, Ko CY, Colangelo LH, Arora A, Hopkins JO, Evans TL, Yothers G. Health-related quality of life outcomes after neoadjuvant chemoradiotherapy for rectal cancer in NRG Oncology/NSABP R-04. Cancer. 2022 Sep 1;128(17):3233-3242. doi: 10.1002/cncr.34341. Epub 2022 Jun 24.
PubMed 35749631
Study at a glance
From the registry record, last updated by the sponsor on 23 Mar 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Clinical Trial Comparing Preoperative Radiation Therapy And Capecitabine With or Without Oxaliplatin With Preoperative Radiation Therapy And Continuous Intravenous Infusion Of 5-Fluorouracil With or Without Oxaliplatin In The Treatment Of Patients With Operable Carcinoma Of The Rectum
- ClinicalTrials.gov ID
- NCT00058474
- Acronym / sponsor ID
- NSABP R-04
- Conditions
- Colorectal Cancer
- Keywords
- stage II rectal cancer, stage III rectal cancer, adenocarcinoma of the rectum
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 1,608 participants (actual)
- Lead sponsor
- NSABP Foundation IncResearch network
- Collaborators
- National Cancer Institute (NCI), Cancer and Leukemia Group B
- Study start
- Jul 2004
- Primary completion
- Aug 2013 (actual)
- Study completion
- May 2016 (estimated)
- First posted
- 9 Apr 2003 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Drugs used in chemotherapy, such as capecitabine, fluorouracil, and oxaliplatin 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.
PURPOSE: This randomized phase III trial is studying radiation therapy and either capecitabine or fluorouracil with or without oxaliplatin and comparing them to see how well they work when given before surgery in treating patients with resectable rectal cancer. It is not yet known whether radiation therapy and either capecitabine or fluorouracil is more effective with or without oxaliplatin in treating rectal cancer.
Detailed description
OBJECTIVES:
Primary
- Compare the rate of local-regional relapse in patients with resectable rectal cancer treated with chemoradiotherapy comprising radiation therapy and either capecitabine or fluorouracil with or without oxaliplatin.
Secondary
- Compare the rate of clinical complete response in patients treated with these regimens.
- Compare the rate of pathologic complete response in patients treated with these regimens.
- Determine the increase in the number of patients who are able to undergo sphincter-saving surgery after treatment with these regimens.
- Correlate genetic patterns and the presence or absence of specific tissue biomarkers with response and prognosis in patients treated with these regimens.
- Compare preoperative quality of life (QOL) of patients treated with oral capecitabine versus continuous infusion with fluorouracil.
- Determine the impact of oxaliplatin on neurotoxicity in patients treated with these regimens.
- Compare the toxic effects of these regimens in these patients.
- Compare the convenience of care in patients treated with these regimens.
- Determine the impact of the type of surgical management on QOL at 1 and 5 years postoperatively in these patients.
- Describe the long-term impact of cancer treatment on symptoms (e.g., vitality and neurotoxicity) and QOL at 5 years after randomization (5-year follow-up visit).
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center, gender, clinical tumor stage (stage II vs stage III), and surgical intent (sphincter saving vs non-sphincter saving). Patients are randomized to 1 of 4 treatment arms.
- Arm 1: Patients receive fluorouracil IV continuously and undergo radiotherapy once daily 5 days a week for 5-6 weeks.
- Arm 2: Patients receive fluorouracil and undergo radiotherapy as in arm 1. Patients also receive oxaliplatin IV over 1 hour once weekly for 5 weeks.
- Arm 3: Patients receive oral capecitabine twice daily and undergo radiotherapy once daily 5 days a week for 5-6 weeks.
- Arm 4: Patients receive capecitabine and undergo radiotherapy as in arm 3. Patients also receive oxaliplatin as in arm 2.
Within 6-8 weeks after the completion of chemoradiotherapy, patients with responding or stable disease undergo surgery. Patients with progressive disease are treated at the discretion of the investigator and continue to be followed.
Quality of life is assessed at baseline, at completion of chemoradiotherapy, and at 1 and 5 years after surgery.
After completion of study treatment, patients are followed every 6 months for 5 years.
PROJECTED ACCRUAL: A total of 1,606 patients will be accrued for this study within 4 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Arm 1: 5-FU + RT | Active comparator | Drug: fluorouracil, Radiation: radiation therapyPatients receive fluorouracil IV continuously and undergo radiation therapy (RT) once daily 5 days a week for 5-6 weeks. |
| Arm 2: 5-FU + RT + Oxaliplatin | Experimental | Drug: fluorouracil, Drug: oxaliplatin, Radiation: radiation therapyPatients receive fluorouracil and undergo RT as in arm 1. Patients also receive oxaliplatin IV over 1 hour once weekly for 5 weeks. |
| Arm 3: Capecitabine + RT | Experimental | Drug: capecitabine, Radiation: radiation therapyPatients receive oral capecitabine twice daily and undergo RT once daily 5 days a week for 5-6 weeks. |
| Arm 4: Capecitabine + RT + Oxaliplatin | Experimental | Drug: capecitabine, Drug: oxaliplatin, Radiation: radiation therapyPatients receive capecitabine and undergo RT as in arm 3. Patients also receive oxaliplatin as in arm 2. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Patients must consent to participate in the study and must have signed and dated an IRB-approved consent form conforming to federal and institutional guidelines.
- Patients must be > 18 years of age.
- Patients must have a life expectancy of 5 years, excluding their diagnosis of cancer (as determined by the investigator), and must have an Eastern Cooperative Oncology Group (ECOG) (Zubrod) performance status of 0 or 1.
- Patients must have a diagnosis of adenocarcinoma of the rectum obtained by a biopsy technique which leaves the major portion of the tumor intact.
- The interval between the initial diagnosis of rectal adenocarcinoma and randomization must be no more than 42 days.
Key exclusion criteria (18 listed)
- Findings of metastatic disease.
- On imaging, clear indication of involvement of the pelvic side wall(s).
- Rectal cancers other than adenocarcinoma, i.e., sarcoma, lymphoma, carcinoid, squamous cell carcinoma, cloacogenic carcinoma, etc.
- History of invasive rectal malignancy, regardless of disease-free interval.
- Pregnancy or lactation at the time of proposed randomization. Eligible patients of reproductive potential (both sexes) must agree to use adequate contraceptive methods.
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 |
|---|---|---|
| capecitabine825 mg/m2 oral daily 5 days a week on days of planned RT | Drug | Arm 3: Capecitabine + RT, Arm 4: Capecitabine + RT + Oxaliplatin |
| fluorouracilAlso: 5-FU225 mg/m2 IV daily continuous infusion | Drug | Arm 1: 5-FU + RT, Arm 2: 5-FU + RT + Oxaliplatin |
| oxaliplatin50 mg/m2 IV 5 days a week on days of planned RT | Drug | Arm 2: 5-FU + RT + Oxaliplatin, Arm 4: Capecitabine + RT + Oxaliplatin |
| radiation therapyAlso: RTGiven 5 days a week for 5-6 weeks | Radiation | Arm 1: 5-FU + RT, Arm 2: 5-FU + RT + Oxaliplatin, Arm 3: Capecitabine + RT, Arm 4: Capecitabine + RT + Oxaliplatin |
Primary outcome
Loco-regional disease control as assessed by evidence of tumor at 3 years
Time frame: Time from randomization to first local recurrence up to 3 years
11 secondary outcomes
Clinical complete response as assessed by digital rectal exam and sigmoidoscopy or proctoscopy at time of definitive analysis
Time frame: Prior to surgery approximately 6 weeks
Pathologic complete response as assessed by gross and microscopic exam of surgical specimens at time of definitive analysis
Time frame: At the time of surgery approximately 6 weeks
Sphincter-saving surgery at time of definitive analysis
Time frame: At the time of surgery approximately 6 weeks
Survival as measured by deaths from any cause at time of definitive analysis
Time frame: From time of randomization through 5 years
Disease-free survival as assessed by recurrence, second primary cancer, or death from any cause at time of definitive analysis
Time frame: From time of randomization through 5 years
Tissue biomarkers as assessed by analysis of tumor tissue using current biotechnology after definitive analysis
Time frame: At the time of surgery approximately 6 weeks
Quality of life as assessed by FACT-C trial outcome index and EORTC CR38 after definitive analysis
Time frame: Assessed prior to therapy and at approximately 5 weeks, 15 months, 5 years
Neurotoxicity as assessed by FACT-NTX scale after definitive analysis
Time frame: Assessed prior to therapy and at approximately 5 weeks, 15 months, 5 years
Symptoms as assessed by fluoropyrimidine symptom scale adapted from SWOG after definitive analysis
Time frame: Assessed prior to therapy and at approximately 5 weeks, 15 months
Vitality as assessed by SF-36 vitality scale after definitive analysis
Time frame: Assessed prior to therapy and at approximately 5 weeks, 15 months, 5 years
Convenience of care as assessed by NSABP C-06 convenience of care scale adapted from ECOG after definitive analysis
Time frame: Assessed prior to therapy and at approximately 5 weeks, 15 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Mar 2016.
- Results publicationGanz PA, Lopa SH, Yothers G, et al.: Comparative effectiveness of sphincter-sparing surgery (SSS) versus abdomino-perineal resection (APR) in rectal cancer: patient-reported outcomes (PROs) from NSABP R-04. [Abstract] J Clin Oncol 30 (Suppl 15): A-3545, 2012.
- Results publicationRoh MS, Yothers GA, O'Connell MJ, et al.: The impact of capecitabine and oxaliplatin in the preoperative multimodality treatment in patients with carcinoma of the rectum: NSABP R-04. [Abstract] J Clin Oncol 29 (Suppl 15): A-3503, 2011.
- Results publication: PubMed 24799484O'Connell MJ, Colangelo LH, Beart RW, Petrelli NJ, Allegra CJ, Sharif S, Pitot HC, Shields AF, Landry JC, Ryan DP, Parda DS, Mohiuddin M, Arora A, Evans LS, Bahary N, Soori GS, Eakle J, Robertson JM, Moore DF Jr, Mullane MR, Marchello BT, Ward PJ, Wozniak TF, Roh MS, Yothers G, Wolmark N. Capecitabine and oxaliplatin in the preoperative multimodality treatment of rectal cancer: surgical end points from National Surgical Adjuvant Breast and Bowel Project trial R-04. J Clin Oncol. 2014 Jun 20;32(18):1927-34. doi: 10.1200/JCO.2013.53.7753. Epub 2014 May 5.
- Results publication: PubMed 24670844Russell MM, Ganz PA, Lopa S, Yothers G, Ko CY, Arora A, Atkins JN, Bahary N, Soori GS, Robertson JM, Eakle J, Marchello BT, Wozniak TF, Beart RW Jr, Wolmark N. Comparative effectiveness of sphincter-sparing surgery versus abdominoperineal resection in rectal cancer: patient-reported outcomes in National Surgical Adjuvant Breast and Bowel Project randomized trial R-04. Ann Surg. 2015 Jan;261(1):144-8. doi: 10.1097/SLA.0000000000000594.
- Derived from this study: PubMed 39080091Peipert JD, Roydhouse J, Tighiouart M, Henry NL, Kim S, Hays RD, Rogatko A, Yothers G, Ganz PA. Overall side effect assessment of oxaliplatin toxicity in rectal cancer patients in NRG oncology/NSABP R04. Qual Life Res. 2024 Nov;33(11):3069-3079. doi: 10.1007/s11136-024-03746-5. Epub 2024 Jul 30.
- Derived from this study: PubMed 35749631Ganz PA, Hays RD, Spritzer KL, Rogatko A, Ko CY, Colangelo LH, Arora A, Hopkins JO, Evans TL, Yothers G. Health-related quality of life outcomes after neoadjuvant chemoradiotherapy for rectal cancer in NRG Oncology/NSABP R-04. Cancer. 2022 Sep 1;128(17):3233-3242. doi: 10.1002/cncr.34341. Epub 2022 Jun 24.
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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.
Norman Wolmark, MD principal investigator
NSABP Foundation Inc
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing capecitabine, fluorouracil and oxaliplatin in people with Colorectal Cancer, run by NSABP Foundation Inc.
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 13 inclusion and 18 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: status not confirmed, as of the sponsor's last update on 23 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.
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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
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?
Loco-regional disease control as assessed by evidence of tumor at 3 years (time frame: Time from randomization to first local recurrence up to 3 years). 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 NCT00058474, which also lists 6 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 23 Mar 2016.