Cancer of RectumPhase 2NORMAL-RNCT02641691
Non-Operative Radiation Management of Adenocarcinoma of the Lower Rectum
A Phase 2 study testing Radiation, Oxaliplatin and Leucovorin in people with Cancer of Rectum and Cancer of the Rectum, run by Washington University School of Medicine at 1 site in United States.
Trial summary
The purpose of this research study is to look at how tumors responds to a short course of radiation (5 days) followed by 8 cycles of chemotherapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cancer of Rectum, Cancer of the Rectum, Neoplasm, Rectum
- What is being tested?
- Radiation, Oxaliplatin and Leucovorin
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 27 May 2016to 29 Mar 2020
- 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
- Diagnosis of biopsy proven stage I-IIIB (cT1-3, N0-1, M0) adenocarcinoma of the rectum; staging must also be based on multidisciplinary evaluation including MRI and/or endorectal ultrasound
- Tumor ≤ 12 cm from anal verge as determined by MRI or endoscopy a
- ECOG performance status 0-2
- At least 18 years of age
- Adequate bone marrow function defined as:
- ANC > 1,500 cells/mm3
Show all 10Show fewer
- Hgb > 8 g/dl
- platelets >100,000 cells/mm3
- Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
- Able to understand and willing to sign an IRB-approved written informed consent document.
Who cannot join
- No clinically detectable (MR, endoscopy or DRE) tumor present
- Prior radiation therapy, chemotherapy or extirpative surgery for rectal cancer.
- Any evidence of disease from another malignancy or history of other malignancy ≤ 3 years previous with the exception of basal cell or squamous cell carcinoma of the skin which were treated with local resection only or carcinoma in situ of the cervix). Patients with history of prostate cancer treated without radiotherapy and no evidence of disease are eligible.
- Currently receiving any investigational agents.
- A history of allergic reaction attributed to compounds of similar chemical or biologic composition to 5FU, oxaliplatin, or leucovorin.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant and/or breastfeeding. Women of childbearing potential must have a negative serum pregnancy test within 14 days of study entry.
- Known HIV-positivity and on combination antiretroviral therapy because of the potential for pharmacokinetic interactions with the study drugs. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: Non-Operative Radiation Management of Adenocarcinoma of the Lower Rectum (NORMAL-R)
The purpose of this research study is to look at how tumors responds to a short course of radiation (5 days) followed by 8 cycles of chemotherapy.
- Conditions
- Cancer of Rectum, Cancer of the Rectum, Neoplasm, Rectum, Rectal Cancer, Rectum Cancer, Rectum Neoplasms
- Being tested
- Radiation, Oxaliplatin, Leucovorin, Fluorouracil
- Medical subject headings
- Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RadiationRadiation
OxaliplatinDrug
Also called Eloxatin®
LeucovorinDrug
Also called Wellcovorin, citrovorum factor, folinic acid, 5-formyl tetrahydrofolate
FluorouracilDrug
Also called 5-Fluorouracil, 5-FU
| Study group | Role | What they receive |
|---|---|---|
| Arm 1: Radiation/Oxaliplatin/Leucovorin/5-FU | Experimental | * Radiotherapy will consist of five fractions, delivered once daily, to a total dose of 25Gy at 5 Gy per fraction.
* An optional concomitant boost may be delivered to the primary tumor of 1-2 Gy per day (30-35 Gy to tumor total). If a boost is given then the maximum allowed dose to small bowel is 25 Gy.
* Chemotherapy should begin two weeks (9-12 working days) after completion of radiotherapy.
* Oxaliplatin will be given intravenous (IV) over 2 hours on Day 1 every 14 days for a maximum of 8 cycles.
* Leucovorin will be given IV over 2 hours on Day 1 every 14 days for a maximum of 8 cycles.
* 5-FU bolus will given IV push on Day 1 every 14 days for a maximum of 8 cycles.
* 5-FU infusion will be given continuous IV on Day 1 over 46 hours every 14 days for a maximum of 8 cycles
* Alternatively, capecitabine/oxaliplatin (CAPE PO 1000 mg/m2 BID days 1-14 Q21 days, oxaliplatin IV 130 mg/m2 IV Q21 days on day 1) x 5 cycles over 15 weeks may be administered instead of FOLFOX Receives: Radiation: Radiation; Drug: Oxaliplatin; Drug: Leucovorin; Drug: Fluorouracil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete Response Rate
- Criteria for complete clinical response:
- No residual gross tumor at procto/sigmoidoscopy, or only erythematous scar or ulcer
- No radiographic evidence of tumor on DRE
- Substantial downsizing on MRI
- No suspicious mesorectal lymph nodes on MRI
- Negative biopsy from scar, ulcer, or former tumor site (if necessary according to surgeon's judgment)
- Criteria for no significant clinical response:
- Residual disease by DRE, endoscopy or MR.
- Increase in primary tumor size upon clinical exam or imaging
- Any new lesions
Measured: 1 year
Secondary outcomes (8)
Prospective Patient Reported Outcomes as Measured by FACT-C Questionnaire
-The FACT-C questionnaire is broken down into physical well-being, social/family well-being, emotional well-being, and functional well-being. The answers range from 0 (not at all) to 4 (very much).
Measured: Baseline
Prospective Patient Reported Outcomes as Measured by FACT-C Questionnaire
-The FACT-C questionnaire is broken down into physical well-being, social/family well-being, emotional well-being, and functional well-being. The answers range from 0 (not at all) to 4 (very much).
Measured: Completion of chemoradiation (approximately 112 days)
Prospective Patient Reported Outcomes as Measured by FACT-C Questionnaire
-The FACT-C questionnaire is broken down into physical well-being, social/family well-being, emotional well-being, and functional well-being. The answers range from 0 (not at all) to 4 (very much).
Measured: 10-14 months after chemoradiation (approximately 16-20 months)
Number of Any Grade 3 or Higher Toxicities
-The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting.
Measured: From start of radiation treatment through 30 days after completion of treatment (approximately 18 weeks)
Number of Post Chemotherapy Grade 3 or Higher Toxicities
-The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting.
Measured: Post-chemotherapy through 1 year follow-up (approximately 1 year and 4 months)
Quality of Anorectal Function as Measured by the FACT-C Questionnaire
-The FACT-C questionnaire has 2 statements about anorectal function and the participant answers 0 (not at all) to 4 (very much)
Measured: Baseline
Quality of Anorectal Function as Measured by the FACT-C Questionnaire
-The FACT-C questionnaire has 2 statements about anorectal function and the participant answers 0 (not at all) to 4 (very much)
Measured: Completion of chemoradiation (approximately 112 days)
Quality of Anorectal Function as Measured by the FACT-C Questionnaire
-The FACT-C questionnaire has 2 statements about anorectal function and the participant answers 0 (not at all) to 4 (very much)
Measured: 10-14 months after chemoradiation (approximately 16-20 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Dec 2015 (estimated)
- Study start27 May 2016
- Primary completion4 Feb 2020
- Study completion29 Mar 2020
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 Cancer of RectumStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Hyun Kim, M.D., Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02641691
- Sponsor's protocol ID
- 201512140
- Acronym
- NORMAL-R
- Status last verified
- Feb 2021
- First submitted
- 23 Dec 2015
- Last updated
- 18 Feb 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
Kim H, Pedersen K, Olsen JR, Mutch MG, Chin RI, Glasgow SC, Wise PE, Silviera ML, Tan BR, Wang-Gillam A, Lim KH, Suresh R, Amin M, Huang Y, Henke LE, Park H, Ciorba MA, Badiyan S, Parikh PJ, Roach MC, Hunt SR. Nonoperative Rectal Cancer Management With Short-Course Radiation Followed by Chemotherapy: A Nonrandomized Control Trial. Clin Colorectal Cancer. 2021 Sep;20(3):e185-e193. doi: 10.1016/j.clcc.2021.03.003. Epub 2021 Apr 7.
PubMed 34001462
Study at a glance
From the registry record, last updated by the sponsor on 18 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Non-Operative Radiation Management of Adenocarcinoma of the Lower Rectum (NORMAL-R)
- ClinicalTrials.gov ID
- NCT02641691
- Acronym / sponsor ID
- NORMAL-R / 201512140
- Conditions
- Cancer of Rectum, Cancer of the Rectum, Neoplasm, Rectum, Rectal Cancer, Rectum Cancer, Rectum Neoplasms
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Study start
- 27 May 2016 (actual)
- Primary completion
- 4 Feb 2020 (actual)
- Study completion
- 29 Mar 2020 (actual)
- First posted
- 29 Dec 2015 (estimated)
- Results
- Posted 18 Feb 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this research study is to look at how tumors responds to a short course of radiation (5 days) followed by 8 cycles of chemotherapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Arm 1: Radiation/Oxaliplatin/Leucovorin/5-FU | Experimental | Radiation: Radiation, Drug: Oxaliplatin, Drug: Leucovorin, Drug: Fluorouracil* Radiotherapy will consist of five fractions, delivered once daily, to a total dose of 25Gy at 5 Gy per fraction. * An optional concomitant boost may be delivered to the primary tumor of 1-2 Gy per day (30-35 Gy to tumor total). If a boost is given then the maximum allowed dose to small bowel is 25 Gy. * Chemotherapy should begin two weeks (9-12 working days) after completion of radiotherapy. * Oxaliplatin will be given intravenous (IV) over 2 hours on Day 1 every 14 days for a maximum of 8 cycles. * Leucovorin will be given IV over 2 hours on Day 1 every 14 days for a maximum of 8 cycles. * 5-FU bolus will given IV push on Day 1 every 14 days for a maximum of 8 cycles. * 5-FU infusion will be given continuous IV on Day 1 over 46 hours every 14 days for a maximum of 8 cycles * Alternatively, capecitabine/oxaliplatin (CAPE PO 1000 mg/m2 BID days 1-14 Q21 days, oxaliplatin IV 130 mg/m2 IV Q21 days on day 1) x 5 cycles over 15 weeks may be administered instead of FOLFOX |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Diagnosis of biopsy proven stage I-IIIB (cT1-3, N0-1, M0) adenocarcinoma of the rectum; staging must also be based on multidisciplinary evaluation including MRI and/or endorectal ultrasound
- Tumor ≤ 12 cm from anal verge as determined by MRI or endoscopy a
- ECOG performance status 0-2
- At least 18 years of age
- Adequate bone marrow function defined as:
Key exclusion criteria (8 listed)
- No clinically detectable (MR, endoscopy or DRE) tumor present
- Prior radiation therapy, chemotherapy or extirpative surgery for rectal cancer.
- Any evidence of disease from another malignancy or history of other malignancy ≤ 3 years previous with the exception of basal cell or squamous cell carcinoma of the skin which were treated with local resection only or carcinoma in situ of the cervix). Patients with history of prostate cancer treated without radiotherapy and no evidence of disease are eligible.
- Currently receiving any investigational agents.
- A history of allergic reaction attributed to compounds of similar chemical or biologic composition to 5FU, oxaliplatin, or leucovorin.
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 | Radiation | Arm 1: Radiation/Oxaliplatin/Leucovorin/5-FU |
| OxaliplatinAlso: Eloxatin® | Drug | Arm 1: Radiation/Oxaliplatin/Leucovorin/5-FU |
| LeucovorinAlso: Wellcovorin, citrovorum factor, folinic acid, 5-formyl tetrahydrofolate | Drug | Arm 1: Radiation/Oxaliplatin/Leucovorin/5-FU |
| FluorouracilAlso: 5-Fluorouracil, 5-FU | Drug | Arm 1: Radiation/Oxaliplatin/Leucovorin/5-FU |
Primary outcome
Complete Response Rate
Time frame: 1 year
* Criteria for complete clinical response: * No residual gross tumor at procto/sigmoidoscopy, or only erythematous scar or ulcer * No radiographic evidence of tumor on DRE * Substantial downsizing on MRI * No suspicious mesorectal lymph nodes on MRI * Negative biopsy from scar, ulcer, or former tumor site (if necessary according to surgeon's judgment) * Criteria for no significant clinical response: * Residual disease by DRE, endoscopy or MR. * Increase in primary tumor size upon clinical exam or imaging * Any new lesions
8 secondary outcomes
Prospective Patient Reported Outcomes as Measured by FACT-C Questionnaire
Time frame: Baseline
Prospective Patient Reported Outcomes as Measured by FACT-C Questionnaire
Time frame: Completion of chemoradiation (approximately 112 days)
Prospective Patient Reported Outcomes as Measured by FACT-C Questionnaire
Time frame: 10-14 months after chemoradiation (approximately 16-20 months)
Number of Any Grade 3 or Higher Toxicities
Time frame: From start of radiation treatment through 30 days after completion of treatment (approximately 18 weeks)
Number of Post Chemotherapy Grade 3 or Higher Toxicities
Time frame: Post-chemotherapy through 1 year follow-up (approximately 1 year and 4 months)
Quality of Anorectal Function as Measured by the FACT-C Questionnaire
Time frame: Baseline
Quality of Anorectal Function as Measured by the FACT-C Questionnaire
Time frame: Completion of chemoradiation (approximately 112 days)
Quality of Anorectal Function as Measured by the FACT-C Questionnaire
Time frame: 10-14 months after chemoradiation (approximately 16-20 months)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Feb 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34001462Kim H, Pedersen K, Olsen JR, Mutch MG, Chin RI, Glasgow SC, Wise PE, Silviera ML, Tan BR, Wang-Gillam A, Lim KH, Suresh R, Amin M, Huang Y, Henke LE, Park H, Ciorba MA, Badiyan S, Parikh PJ, Roach MC, Hunt SR. Nonoperative Rectal Cancer Management With Short-Course Radiation Followed by Chemotherapy: A Nonrandomized Control Trial. Clin Colorectal Cancer. 2021 Sep;20(3):e185-e193. doi: 10.1016/j.clcc.2021.03.003. Epub 2021 Apr 7.
- Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of MedicineLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Hyun Kim, M.D. principal investigator
Washington University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Radiation, Oxaliplatin and Leucovorin in people with Cancer of Rectum and Cancer of the Rectum, run by Washington University School of Medicine at 1 site in United States.
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 8 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 18 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 18 Feb 2021). 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?
Complete Response Rate (time frame: 1 year). 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 NCT02641691, which also lists 1 linked publication.
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 18 Feb 2021; AzTrials last refreshed its copy on 8 Nov 2026.