Rectal Cancer
Conditions
Keywords
rectal, colon, PLACEBO, RIFAXIMIN, metronidazole, 11-045
Brief summary
The most common long-term problems after rectal surgery are bowel problems. These problems can include needing to pass bowel movements a lot, loose or mushy stools, inability to fully clear your bowels, and/or poor control of gas and stool. The investigators believe that a major cause of these problems is too much bacteria in the bowel and treatment with antibiotic tablets will hopefully help improve these bowel problems. In order to test this idea, the Colorectal Surgery Service of Memorial Sloan Kettering Cancer Center is sponsoring a clinical trial. This trial will compare the antibiotic rifaximin and a placebo (a harmless tablet that has no effect) in the treatment of these bowel problems. Following this we will attempt to see if another antibiotic metronidazole also helps to treat these bowel problems. Both Metronidazole and rifaximin are well established drugs that have minimal side effects.
Interventions
DRUGRifaximin
Pt will receive rifaximin 400mg bid for 4 weeks. Patients will at this stage on a volunteer basis be asked to submit stool samples and undertake a breath test. Patients will receive the respective treatment for four weeks. Following cessation of treatment all patients will be assessed using the BFI and respective patients will have repeat stool sampling and breath testing. Patients will then have these tests repeated 4 weeks later. This corresponds to 8 weeks after the start of the trial. For those patients not undertaking stool and breath testing, they will be reminded by phone, mail or email to fill out the BFI. Before and during the trial patients will be asked to fill out a weekly stool diary to evaluate trends on bowel function.
DRUGPlacebo
Pt will receive placebo bid for 4 weeks. Patients will at this stage on a volunteer basis be asked to submit stool samples and undertake a breath test. Patients will receive the respective treatment for four weeks. Following cessation of treatment all patients will be assessed using the BFI and respective patients will have repeat stool sampling and breath testing. Patients will then have these tests repeated 4 weeks later. This corresponds to 8 weeks after the start of the trial. For those patients not undertaking stool and breath testing, they will be reminded by phone, mail or email to fill out the BFI. Before and during the trial patients will be asked to fill out a weekly stool diary to evaluate trends on bowel function.
Sponsors
Memorial Sloan Kettering Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with a history of rectal cancer treated with an anterior resection preformed at MSKCC (tumor at or below 12cm from anal verge) with restoration of bowel continuity ≥1 and ≤ 5 years. (Patients may also have had procedures to construct neo-rectums including j-pouch, coloplasty, and end to side anastomosis). * Patients ≥ 21 years of age. * Presence of anterior resection symptoms by patients own assessment. These symptoms may include any of the following: incomplete evacuation, clustering of bowel motions, frequency of bowel motions, unformed stool, excessive flatus, or incontinence of flatus and/or feces.
Exclusion criteria
* Local recurrence of rectal cancer. * Antibiotic treatment within the last 4 weeks for any condition. * Pregnancy or breast feeding.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants Who Completed MSKCC Bowel Function Instrument (BFI Score) in Patients Following Anterior Resection (AR) or Sphincter Preserving Surgery (SPS) for Rectal Cancer. | 1 year |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To Determine if Reduction in Intestinal Bacterial Quantity Correlates With Improvement in Bowel Symptoms (BFI Score). | 1 year | — |
| To Explore the Bacterial Composition of Stool Before and After Antibiotic Treatment. | 1 year | — |
| To Identify Dynamic Changes in Bowel Function During and After Antibiotic Treatment Using a Bowel Function Log. | 1 year | — |
| Efficacy of Metronidazole | 1 year | in the treatment of bowel dysfunction as measured by the MSKCC BFI in patients following AR or SPS for rectal cancer for patients who have no improvement following treatment with rifaximin or placebo. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pts Receiving Rifaximin This group will receive rifaximin 400mg bid for 4 weeks. At 1 - 24 months after completion of the phase III portion of the trial, patients will be contacted by phone and given the option of receiving metronidazole in a followup, single arm study in which all patients receive the antibiotic. Patients who wish to participate will be mailed a drug prescription for a 3 week course of metronidazole 500mgs tid as well as the BFI forms and stool diary. Pretreatment and post treatment BFI scores will be collected and analyzed for change in bowel function as was done in the initial Phase III study.
Rifaximin: Pt will receive rifaximin 400mg bid for 4 weeks. Patients will at this stage on a volunteer basis be asked to submit stool samples and undertake a breath test. Patients will receive the respective treatment for four weeks. Following cessation of treatment all patients will be assessed using the BFI and respective patients will have repeat stool sampling and breath testing. Patients will then have these tests repeated 4 weeks later. This corresponds to 8 weeks after the start of the trial. For those patients not undertaking stool and breath testing, they will be reminded by phone, mail or email to fill out the BFI. Before and during the trial patients will be asked to fill out a weekly stool diary to evaluate trends on bowel function. | 36 |
| Pts Receiving Placebo This group will receive a placebo bid for 4 weeks. At 1 - 24 months after completion of the phase III portion of the trial, patients will be contacted by phone and given the option of receiving metronidazole in a followup, single arm study in which all patients receive the antibiotic. Patients who wish to participate will be mailed a drug prescription for a 3 week course of metronidazole 500mgs tid as well as the BFI forms and stool diary. Pretreatment and post treatment BFI scores will be collected and analyzed for change in bowel function as was done in the initial Phase III study.
Placebo: Pt will receive placebo bid for 4 weeks. Patients will at this stage on a volunteer basis be asked to submit stool samples and undertake a breath test. Patients will receive the respective treatment for four weeks. Following cessation of treatment all patients will be assessed using the BFI and respective patients will have repeat stool sampling and breath testing. Patients will then have these tests repeated 4 weeks later. This corresponds to 8 weeks after the start of the trial. For those patients not undertaking stool and breath testing, they will be reminded by phone, mail or email to fill out the BFI. Before and during the trial patients will be asked to fill out a weekly stool diary to evaluate trends on bowel function. | 33 |
| Total | 69 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Failed to complete BFI | 3 | 2 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Stopped taking medication | 2 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Total | Pts Receiving Rifaximin | Pts Receiving Placebo |
|---|---|---|---|
| Age, Continuous | 58.16 years STANDARD_DEVIATION 9.69 | 55.47 years STANDARD_DEVIATION 8.87 | 61.09 years STANDARD_DEVIATION 10.51 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 4 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 62 Participants | 32 Participants | 30 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 64 Participants | 33 Participants | 31 Participants |
| Region of Enrollment United States | 69 Participants | 36 Participants | 33 Participants |
| Sex: Female, Male Female | 37 Participants | 17 Participants | 20 Participants |
| Sex: Female, Male Male | 32 Participants | 19 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 36 | 0 / 33 |
| other Total, other adverse events | 0 / 36 | 0 / 33 |
| serious Total, serious adverse events | 0 / 36 | 1 / 33 |
Outcome results
Primary
Number of Participants Who Completed MSKCC Bowel Function Instrument (BFI Score) in Patients Following Anterior Resection (AR) or Sphincter Preserving Surgery (SPS) for Rectal Cancer.
Time frame: 1 year
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Pts Receiving Rifaximin | Number of Participants Who Completed MSKCC Bowel Function Instrument (BFI Score) in Patients Following Anterior Resection (AR) or Sphincter Preserving Surgery (SPS) for Rectal Cancer. | Completed BFI | 30 Participants |
| Pts Receiving Rifaximin | Number of Participants Who Completed MSKCC Bowel Function Instrument (BFI Score) in Patients Following Anterior Resection (AR) or Sphincter Preserving Surgery (SPS) for Rectal Cancer. | Did not complete BFI | 6 Participants |
| Pts Receiving Placebo | Number of Participants Who Completed MSKCC Bowel Function Instrument (BFI Score) in Patients Following Anterior Resection (AR) or Sphincter Preserving Surgery (SPS) for Rectal Cancer. | Completed BFI | 27 Participants |
| Pts Receiving Placebo | Number of Participants Who Completed MSKCC Bowel Function Instrument (BFI Score) in Patients Following Anterior Resection (AR) or Sphincter Preserving Surgery (SPS) for Rectal Cancer. | Did not complete BFI | 6 Participants |
Secondary
Efficacy of Metronidazole
in the treatment of bowel dysfunction as measured by the MSKCC BFI in patients following AR or SPS for rectal cancer for patients who have no improvement following treatment with rifaximin or placebo.
Time frame: 1 year
Population: N/A Data were not collected
Secondary
To Determine if Reduction in Intestinal Bacterial Quantity Correlates With Improvement in Bowel Symptoms (BFI Score).
Time frame: 1 year
Population: N/A Data were not collected
Secondary
To Explore the Bacterial Composition of Stool Before and After Antibiotic Treatment.
Time frame: 1 year
Population: N/A Data were not collected
Secondary
To Identify Dynamic Changes in Bowel Function During and After Antibiotic Treatment Using a Bowel Function Log.
Time frame: 1 year
Population: N/A data were not completed