Mucinous Adenocarcinoma of the RectumPhase 1NCT02270606
Phase I Study of Neoadjuvant Radiotherapy With 5-Fluorouracil for Rectal Cancer
A Phase 1 study testing intensity-modulated radiation therapy, fluorouracil and oxaliplatin in people with Mucinous Adenocarcinoma of the Rectum and Recurrent Rectal Cancer, run by Virginia Commonwealth University at 1 site in United States.
Trial summary
This phase I trial studies the side effects and best dose of fluorouracil when given together with radiation therapy followed by combination chemotherapy before and after surgery in treating patients with rectal cancer that has spread from where it started to nearby tissue or lymph nodes. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Mucinous Adenocarcinoma of the Rectum, Recurrent Rectal Cancer, Signet Ring Adenocarcinoma of the Rectum
- What is being tested?
- intensity-modulated radiation therapy, fluorouracil and oxaliplatin
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- 4 Dec 2014to 13 May 2021
- Phase
- Phase 1
- 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
- Pathologically proven diagnosis of adenocarcinoma of the rectum (located below the peritoneal reflection or begins within 15 cm of the anal verge on flexible endoscopy) within 90 days of registration; diagnosis of rectal adenocarcinoma must be obtained by biopsy technique that does not completely excise the lesion (eg, fine needle aspiration, core needle biopsy)
- Clinically determined to be clinically staged (American Joint Committee on Cancer (AJCC) 7th edition [ed.]) T3-4 N0 M0 or T any N1-2 M0 based upon the following minimum diagnostic workup within 90 days prior to registration:
- Colonoscopy
- History/physical examination (including medication history screen for contraindications)
- Contrast-enhanced imaging of the abdomen and pelvis either by computed tomography (CT), magnetic resonance imaging (MRI), or whole body positron emission tomography (PET)-CT (preferred)
- Chest x-ray (or CT) of the chest to exclude distant metastases (except for those who have had whole body PET-CT per above bullet point)
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- Transrectal ultrasound (TRUS) or MRI for T staging
- Eastern Cooperative Oncology Group (ECOG) performance status =< 1
- Absolute neutrophil count (ANC) >= 1,800 cells/mm^3
- Platelets >= 100,000 cells/mm^3
- Hemoglobin >= 8.0 g/dL (note: the use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 8.0 g/dL is acceptable)
- Aspartate aminotransferase (AST) < 2.5 x upper limit of normal (ULN)
- Alkaline phosphatase < 2.5 x ULN
- Bilirubin =< 1.5 ULN
- Calculated creatinine clearance (CrCl) > 50 mL/min using Cockcroft-Gault formula
- Must be deemed a candidate for curative resection by the surgical oncologist who will be performing the operation
- Must provide study-specific informed consent prior to study entry
- Must have a negative serum pregnancy test
Who cannot join
- Prior radiotherapy to the region of the body that would result in overlap of RT fields with the current protocol treatment
- Severe, active comorbidity, defined as follows:
- Unstable angina and/or congestive heart failure requiring hospitalization within the last 12 months
- Transmural myocardial infarction within the last 6 months
- Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
- Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days prior to registration
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- Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
- Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that human immunodeficiency virus (HIV) testing is not required for entry into this protocol
- 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 treatment protocol or follow up
- Known, existing uncontrolled coagulopathy; subjects on therapeutic anticoagulation may be enrolled provided that they have been clinically stable on anti-coagulation for at least 2 weeks
- Major surgery within 28 days of study enrollment (other than diverting colostomy)
- Crohn's disease or ulcerative colitis requiring hospitalization, surgery or immunosuppressive medications
- Prior allergic reaction to 5-Fluorouracil or oxaliplatin
- Any evidence of distant metastases (M1)
- Extension of malignant disease into the anal canal
- Pregnant as determined by a positive serum pregnancy test within 14 days prior to registration on study (for females of childbearing potential)
Trial locations and contacts
1 site in 1 country.
United States1 site
Virginia Commonwealth University/Massey Cancer Center
Richmond, Virginia, 23219
About this study
Official title: Phase I Study of Neoadjuvant Short Course Radiotherapy Concurrent With Infusional 5-Fluorouracil for the Treatment of Locally Advanced Rectal Cancer
This phase I trial studies the side effects and best dose of fluorouracil when given together with radiation therapy followed by combination chemotherapy before and after surgery in treating patients with rectal cancer that has spread from where it started to nearby tissue or lymph nodes. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Drugs used in chemotherapy, such as fluorouracil, leucovorin calcium, and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving more than one drug (combination chemotherapy) before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving additional combination chemotherapy after surgery may kill any remaining tumor cells. Giving radiation therapy and fluorouracil followed by combination chemotherapy before and after surgery may be a better treatment for rectal cancer.
Read the detailed description
OUTLINE: This is a dose-escalation study of fluorouracil.
CHEMORADIATION: Patients undergo intensity-modulated radiation therapy (IMRT) once daily (QD) over 5 days for a total of 5 fractions and concurrently receive fluorouracil intravenously (IV) continuously over 96 hours.
PREOPERATIVE CHEMOTHERAPY: Within 2 weeks of completing chemoradiation, patients receive oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV as a push followed by IV continuously over 46 hours on day 1. Treatment repeats every 14 days for 4 courses in the absence of disease progression or unacceptable toxicity.
SURGERY: Within 4-8 weeks of completing preoperative chemotherapy, patients undergo total mesorectal excision.
POSTOPERATIVE CHEMOTHERAPY: Within 4-8 weeks after surgery, patients receive oxaliplatin, leucovorin calcium, and fluorouracil as in preoperative chemotherapy. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 1 year or until removal from the study or death, whichever occurs first.
- Conditions
- Mucinous Adenocarcinoma of the Rectum, Recurrent Rectal Cancer, Signet Ring Adenocarcinoma of the Rectum, Rectal Adenocarcinoma, Stage IIA Rectal Cancer, Stage IIB Rectal Cancer
- Being tested
- intensity-modulated radiation therapy, fluorouracil, oxaliplatin, leucovorin calcium, therapeutic conventional surgery
- Keywords
- Rectum
- Medical subject headings
- Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
intensity-modulated radiation therapyRadiation
Also called IMRT
Undergo IMRT
fluorouracilDrug
Also called 19893, 2,4-Dioxo-5-fluoropyrimidine,, 5-Fluoro-2,4(1H,3H)-pyrimidinedione,, Actino-Hermal, Adrucil
Given IV
oxaliplatinDrug
Also called 1-OHP, 63121-00-6, [(1R,-2R)-1,2-cyclohexanediamine-N,N'], diaminocyclohexane, oxalatoplatinum, Dacotin
Given IV
Also called 1492-18-8, 27275, 3590, 4292,, 5-formyl tetrahydrofolate, Adinepar, calcium (6S)-folinate
Given IV
therapeutic conventional surgeryProcedure or surgery
Undergo total mesorectal excision
| Study group | Role | What they receive |
|---|---|---|
| Treatment(IMRT,fluorouracil,chemotherapy,surgery) | Experimental | CHEMORADIATION:Patients undergo Intensity Modulated Radiation Therapy (IMRT) once a day over 5 days for total of 5 fractions and concurrently receive fluorouracil IV continuously over 96 hours.
PREOPERATIVE CHEMOTHERAPY:Within 2 weeks of completing chemoradiation, patients receive oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV as a push followed by IV continuously over 46 hours on day 1.Treatment repeats every 14 days for 4 courses in absence of disease progression or unacceptable toxicity.
SURGERY:Within 4-8 weeks of completing preoperative chemotherapy, patients undergo total mesorectal excision as therapeutic conventional surgery.
POSTOPERATIVE CHEMOTHERAPY:Within 4-8 weeks after surgery, patients receive oxaliplatin, leucovorin calcium, and fluorouracil(preoperative chemotherapy).Treatment repeats every 14 days for 6 courses in absence of disease progression or unacceptable toxicity. Receives: Radiation: intensity-modulated radiation therapy; Drug: fluorouracil; Drug: oxaliplatin; Drug: leucovorin calcium; Procedure: therapeutic conventional surgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose limiting toxicity for continuous infusional 5-Fluorouracil given concurrently with short course pelvic radiation
To determine the maximum tolerated dose of continuous infusional 5-Fluorouracil, up to a target dose of 200 mg/m^2/day, given concurrently with short course radiation followed by neoadjuvant FOLFOX chemotherapy and planned surgical resection for locally advanced rectal cancer. Assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.
Measured: Up to 21 days
Secondary outcomes (7)
Pathological response rate for subjects treated with concurrent 5-FU
To determine the rates of pathologic response for subjects treated with 5-FU together with neoadjuvant, short course pelvic RT.
Measured: Up to at least 5 years
Complete response rate with radiographic imaging prior to surgery
To determine the rate of complete response prior to surgery.
Measured: Up to 8 weeks after completion of pre-operative chemotherapy
Three-year rate of local-regional recurrence for all subjects enrolled on the study
To determine the rates of local-regional recurrence for subjects treated with 5-FU together with neoadjuvant, short course pelvic RT.
Measured: 3 years
Adverse events at any time
To determine the incidence of all toxicity (gastrointestinal and non-gastrointestinal) associated with protocol treatment in the preoperative period, the postoperative period, and therefore assess the tolerability of the combination regimen.
Measured: 30 days after surgery
Three-year rate of disease-free survival for all subjects enrolled on the study
To determine the disease-free survival for subjects treated with 5-FU together with neoadjuvant, short course pelvic RT.
Measured: 3 years
Postoperative morbidity rates
Measured: Up to 30 days after surgery
Postoperative mortality rates
Measured: Up to 30 days after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Oct 2014 (estimated)
- Study start4 Dec 2014
- Primary completion14 May 2018
- Study completion13 May 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Mucinous Adenocarcinoma of the RectumStudies of the same condition, open and under way.
- More trials run by Virginia Commonwealth UniversityThe 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Virginia Commonwealth University
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Emma C Fields, MD, Principal investigator, Massey Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02270606
- Sponsor's protocol ID
- MCC-14-10491
- Other IDs
- NCI-2014-02089, P30CA016059
- Status last verified
- Jul 2021
- First submitted
- 16 Oct 2014
- Last updated
- 20 Jul 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of Neoadjuvant Short Course Radiotherapy Concurrent With Infusional 5-Fluorouracil for the Treatment of Locally Advanced Rectal Cancer
- ClinicalTrials.gov ID
- NCT02270606
- Acronym / sponsor ID
- MCC-14-10491
- Conditions
- Mucinous Adenocarcinoma of the Rectum, Recurrent Rectal Cancer, Signet Ring Adenocarcinoma of the Rectum, Rectal Adenocarcinoma, Stage IIA Rectal Cancer, Stage IIB Rectal Cancer
- Keywords
- Rectum
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Virginia Commonwealth UniversityUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 4 Dec 2014 (actual)
- Primary completion
- 14 May 2018 (actual)
- Study completion
- 13 May 2021 (actual)
- First posted
- 21 Oct 2014 (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.
This phase I trial studies the side effects and best dose of fluorouracil when given together with radiation therapy followed by combination chemotherapy before and after surgery in treating patients with rectal cancer that has spread from where it started to nearby tissue or lymph nodes. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Drugs used in chemotherapy, such as fluorouracil, leucovorin calcium, and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving more than one drug (combination chemotherapy) before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving additional combination chemotherapy after surgery may kill any remaining tumor cells. Giving radiation therapy and fluorouracil followed by combination chemotherapy before and after surgery may be a better treatment for rectal cancer.
Detailed description
OUTLINE: This is a dose-escalation study of fluorouracil.
CHEMORADIATION: Patients undergo intensity-modulated radiation therapy (IMRT) once daily (QD) over 5 days for a total of 5 fractions and concurrently receive fluorouracil intravenously (IV) continuously over 96 hours.
PREOPERATIVE CHEMOTHERAPY: Within 2 weeks of completing chemoradiation, patients receive oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV as a push followed by IV continuously over 46 hours on day 1. Treatment repeats every 14 days for 4 courses in the absence of disease progression or unacceptable toxicity.
SURGERY: Within 4-8 weeks of completing preoperative chemotherapy, patients undergo total mesorectal excision.
POSTOPERATIVE CHEMOTHERAPY: Within 4-8 weeks after surgery, patients receive oxaliplatin, leucovorin calcium, and fluorouracil as in preoperative chemotherapy. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 1 year or until removal from the study or death, whichever occurs first.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment(IMRT,fluorouracil,chemotherapy,surgery) | Experimental | Radiation: intensity-modulated radiation therapy, Drug: fluorouracil, Drug: oxaliplatin, Drug: leucovorin calcium, Procedure: therapeutic conventional surgeryCHEMORADIATION:Patients undergo Intensity Modulated Radiation Therapy (IMRT) once a day over 5 days for total of 5 fractions and concurrently receive fluorouracil IV continuously over 96 hours. PREOPERATIVE CHEMOTHERAPY:Within 2 weeks of completing chemoradiation, patients receive oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV as a push followed by IV continuously over 46 hours on day 1.Treatment repeats every 14 days for 4 courses in absence of disease progression or unacceptable toxicity. SURGERY:Within 4-8 weeks of completing preoperative chemotherapy, patients undergo total mesorectal excision as therapeutic conventional surgery. POSTOPERATIVE CHEMOTHERAPY:Within 4-8 weeks after surgery, patients receive oxaliplatin, leucovorin calcium, and fluorouracil(preoperative chemotherapy).Treatment repeats every 14 days for 6 courses in absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Pathologically proven diagnosis of adenocarcinoma of the rectum (located below the peritoneal reflection or begins within 15 cm of the anal verge on flexible endoscopy) within 90 days of registration; diagnosis of rectal adenocarcinoma must be obtained by biopsy technique that does not completely excise the lesion (eg, fine needle aspiration, core needle biopsy)
- Clinically determined to be clinically staged (American Joint Committee on Cancer (AJCC) 7th edition [ed.]) T3-4 N0 M0 or T any N1-2 M0 based upon the following minimum diagnostic workup within 90 days prior to registration:
- Eastern Cooperative Oncology Group (ECOG) performance status =< 1
- Absolute neutrophil count (ANC) >= 1,800 cells/mm^3
- Platelets >= 100,000 cells/mm^3
Key exclusion criteria (16 listed)
- Prior radiotherapy to the region of the body that would result in overlap of RT fields with the current protocol treatment
- Severe, active comorbidity, defined as follows:
- Prior allergic reaction to 5-Fluorouracil or oxaliplatin
- Any evidence of distant metastases (M1)
- Extension of malignant disease into the anal canal
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 |
|---|---|---|
| intensity-modulated radiation therapyAlso: IMRTUndergo IMRT | Radiation | Treatment(IMRT,fluorouracil,chemotherapy,surgery) |
| fluorouracilAlso: 19893, 2,4-Dioxo-5-fluoropyrimidine,, 5-Fluoro-2,4(1H,3H)-pyrimidinedione,, Actino-Hermal, AdrucilGiven IV | Drug | Treatment(IMRT,fluorouracil,chemotherapy,surgery) |
| oxaliplatinAlso: 1-OHP, 63121-00-6, [(1R,-2R)-1,2-cyclohexanediamine-N,N'], diaminocyclohexane, oxalatoplatinum, DacotinGiven IV | Drug | Treatment(IMRT,fluorouracil,chemotherapy,surgery) |
| leucovorin calciumAlso: 1492-18-8, 27275, 3590, 4292,, 5-formyl tetrahydrofolate, Adinepar, calcium (6S)-folinateGiven IV | Drug | Treatment(IMRT,fluorouracil,chemotherapy,surgery) |
| therapeutic conventional surgeryUndergo total mesorectal excision | Procedure or surgery | Treatment(IMRT,fluorouracil,chemotherapy,surgery) |
Primary outcome
Dose limiting toxicity for continuous infusional 5-Fluorouracil given concurrently with short course pelvic radiation
Time frame: Up to 21 days
To determine the maximum tolerated dose of continuous infusional 5-Fluorouracil, up to a target dose of 200 mg/m^2/day, given concurrently with short course radiation followed by neoadjuvant FOLFOX chemotherapy and planned surgical resection for locally advanced rectal cancer. Assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.
7 secondary outcomes
Pathological response rate for subjects treated with concurrent 5-FU
Time frame: Up to at least 5 years
Complete response rate with radiographic imaging prior to surgery
Time frame: Up to 8 weeks after completion of pre-operative chemotherapy
Three-year rate of local-regional recurrence for all subjects enrolled on the study
Time frame: 3 years
Adverse events at any time
Time frame: 30 days after surgery
Three-year rate of disease-free survival for all subjects enrolled on the study
Time frame: 3 years
Postoperative morbidity rates
Time frame: Up to 30 days after surgery
Postoperative mortality rates
Time frame: Up to 30 days after surgery
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jul 2021.
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.
Emma C Fields, MD principal investigator
Massey Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing intensity-modulated radiation therapy, fluorouracil and oxaliplatin in people with Mucinous Adenocarcinoma of the Rectum and Recurrent Rectal Cancer, run by Virginia Commonwealth University 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 18 inclusion and 16 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 20 Jul 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Dose limiting toxicity for continuous infusional 5-Fluorouracil given concurrently with short course pelvic radiation (time frame: Up to 21 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 20 Jul 2021.