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Trial registered on ANZCTR


Registration number
ACTRN12621001403820
Ethics application status
Approved
Date submitted
26/07/2021
Date registered
18/10/2021
Date last updated
3/08/2024
Date data sharing statement initially provided
18/10/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
A phase II, multi-site, double blind, randomised placebo-controlled feasibility trial of crushed oral famotidine for management of Inoperable Malignant Bowel Obstruction (IMBO)
Scientific title
A phase II, multi-site, double blind, randomised placebo-controlled feasibility trial of crushed oral famotidine for management of Inoperable Malignant Bowel Obstruction (IMBO)
Secondary ID [1] 302049 0
054/20
Universal Trial Number (UTN)
Trial acronym
IMBO Pilot study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Bowel Obstruction 318646 0
Malignant Bowel Obstruction 323349 0
Bowel cancer 323350 0
Condition category
Condition code
Cancer 316659 316659 0 0
Bowel - Small bowel (duodenum and ileum)
Cancer 316660 316660 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Crushed Famotidine tablet for oral consumption, 40 mg every 24 hours for 5 days, within 24 hours of baseline assessments, administered in a thick fluid such as yoghurt or apple puree. Administered by nursing staff, witnessed and recorded as administered within the medication record. The medical record is considered the record of adherence.
Crushed Dexamethasone for oral consumption, 8mg once per day in the morning for 5 days and to be commenced before midday on the first day or the next morning (if baseline assessments are completed in the afternoon), administered in a thick fluid such as yoghurt or apple puree. Administered by nursing staff, witnessed and recorded as administered within the medication record. The medical record is considered the record of adherence.
Isotonic fluid administered as a parenteral infusion, at 10 – 20 mL / kg / 24-hours, commenced on on completion of the baseline assessments (unless dehydrated at the time the study is commenced where the treating clinician’s discretion may be used in the first 24 hours).
Intervention code [1] 318352 0
Treatment: Drugs
Comparator / control treatment
Crushed oral placebo for oral consumption every 24 hours for a total of 5 days, within 24 hours of baseline assessments. Administered by nursing staff, witnessed and recorded as administered within the medication record. The medical record is considered the record of adherence. The placebo contains PROSOLV® EASYTab SP which contains: Microcrystalline Cellulose, Colloidal Silicon Dioxide, Sodium Starch Glycolate and Sodium Stearyl Fumarate.
Crushed Dexamethasone for oral consumption, 8mg once per day in the morning for 5 days and to be commenced before midday on the first day or the next morning (if baseline assessments are completed in the afternoon), administered in a thick fluid such as yoghurt or apple puree. Administered by nursing staff, witnessed and recorded as administered within the medication record. The medical record is considered the record of adherence.
Isotonic fluid administered as a parenteral infusion, at 10 – 20 mL / kg / 24-hours, commenced on on completion of the baseline assessments (unless dehydrated at the time the study is commenced where the treating clinician’s discretion may be used in the first 24 hours).
Control group
Placebo

Outcomes
Primary outcome [1] 324785 0
The primary outcome is whether this study is feasible to extend to a fully powered phase III clinical trial.

Feasibility is defined as:
1. An average of one participant identified per site every eight weeks using recruitment tracking data bases;
2. One participant recruited per site every 12 weeks using recruitment racking databases; and
3. Collect data for >80% of people randomised, to the primary endpoint of 120 hours or study exit assessed by reviewing the data entry into the study data base..
Timepoint [1] 324785 0
On completion of the study
Secondary outcome [1] 385731 0
Safety and tolerability. Safety and tolerability will be measured by the number of possible or probably related grade 4 or 5 (using the Common Terminology Criteria for Adverse Events (CTCAE5.0) intervention toxicities.
Causality will be assessed using 'The WHO-UMC system for standardised case causality assessment'.
Possible adverse reactions are symptoms such as infusion site reaction, assessed by clinicians, and abdominal symptoms such as flatulence, abdominal pain, reported by the participant, and hypoglycemia, assessed by bedside blood sugar monitoring.
Timepoint [1] 385731 0
The types and severity of AEs and SAEs will be recorded from the initiation of treatment until 4 weeks after treatment cessation (follow-up period).
Secondary outcome [2] 385732 0
Changes in the frequency of vomiting in each arm assessed using participant self report and accessing patient medical record.
Timepoint [2] 385732 0
Vomiting will be assessed each 24 hours up to 120 hours after commencing therapy
Secondary outcome [3] 385733 0
Rates of Inoperable Malignant Bowel Obstruction (IMBO) resolution, clinician assessed defined as a cessation of vomiting for a period of 24-hours or greater with flatus.
Timepoint [3] 385733 0
From the initiation of treatment until 4 weeks after treatment cessation (follow-up period).
Secondary outcome [4] 385734 0
Overall survival via accessing the patient clinical record.
Timepoint [4] 385734 0
From the initiation of treatment until 4 weeks after treatment cessation (follow-up period).
Secondary outcome [5] 385735 0
Patient health related quality of life using the EQ-5D-5L questionnaire. The EORTC QLQ-C15-PAL will be administered if the patient is well enough to complete a second questionnaire.
Timepoint [5] 385735 0
At initiation of treatment, cessation of treatment and weekly for for 4 weeks after treatment cessation (follow-up period).
Secondary outcome [6] 385736 0
Caregiver health related quality of life using the Caregiver Quality of Life Index-Cancer (CQOLC) scale
Timepoint [6] 385736 0
At initiation of treatment, cessation of treatment and weekly for for 4 weeks after treatment cessation (follow-up period).
Secondary outcome [7] 385738 0
Efficacy of treatment using measures for treatment failure (use of nasogastric tube, increases in use of symptomatic medications, progression to surgery, increasing adverse events, and commencement of alternate treatment by the treating clinician). This information will be taken from the medical record.
Timepoint [7] 385738 0
From the initiation of treatment, every 24 hours for 120 hours, or until treatment cessation if prior to 120 hours, and weekly for 4 weeks after treatment cessation (follow-up period).
Secondary outcome [8] 400076 0
Efficacy of treatment using measures for the restoration of (limited) bowel function (through documentation of oral intake, flatus and resumption of bowel function), information will be taken from the medical record, or participant reported if in follow-up and discharged from hospital.
Timepoint [8] 400076 0
From the initiation of treatment, every 24 hours for 120 hours, or until treatment cessation if prior to 120 hours, and weekly for 4 weeks after treatment cessation (follow-up period).
Secondary outcome [9] 400077 0
Efficacy of treatment using global measures including performance status (AKPS)
Timepoint [9] 400077 0
At initiation of treatment, cessation of treatment and weekly for for 4 weeks after treatment cessation (follow-up period).
Secondary outcome [10] 401323 0
Efficacy of treatment using global measures of performance status using symptom scores for pain on a numeric rating scale of 0-10.
Timepoint [10] 401323 0
At initiation of treatment, every 24 hours for 120 hours, or until cessation of treatment if prior to 120 hours, and weekly for for 4 weeks after treatment cessation (follow-up period).
Secondary outcome [11] 401324 0
Efficacy of treatment using global measures of quality of life using the EQ-5D-5L.
Timepoint [11] 401324 0
At initiation of treatment, cessation of treatment and weekly for for 4 weeks after treatment cessation (follow-up period).
Secondary outcome [12] 401325 0
Efficacy of treatment using global measures of quality of life using the EORTC QLQ C15 Pal.
Timepoint [12] 401325 0
At initiation of treatment, cessation of treatment and weekly for for 4 weeks after treatment cessation (follow-up period).
Secondary outcome [13] 401328 0
Efficacy of treatment using general measure of survival using date of death taken from the medical record.
Timepoint [13] 401328 0
On completion of 4 weeks of follow-up, or earlier if death is prior to 4 weeks.

Eligibility
Key inclusion criteria
• Advanced cancer;
• Clinically confirmed bowel obstruction at any level with vomiting that precipitates a hospital admission or change in clinical care;
• Deemed by two consultant level medical practitioners that this person has a bowel obstruction (partial or complete) for which immediate surgery is not indicated;
• Disease-modifying therapy (surgery, chemotherapy, radiotherapy, hormone therapy; biological/targeted therapies) is deemed by relevant practitioners unlikely to change the bowel obstruction;
• If participant has a nasogastric tube (NGT), final decompression must be at least 12 hours before treatment start;
• Participant is capable of completing assessments and complying with the study procedures;
• Record a St Louis Mental Status Exam Score (SLUMS) of greater than or equal to 23 or as deemed suitable by the site principal investigator; and
• Participant is able to give fully informed, written consent.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Previous adverse reaction to any of the study medications;
• Calculated creatinine clearance <10 mL / min using the Modification of Diet in Renal Disease Study (MDRD) formula;
• Venting or feeding gastrostomy or jejunostomy;
• Participant has a NGT that, in the investigator’s opinion, cannot be clamped for the duration of treatment; and
• Oral food intake that cannot be reduced to clear fluids

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
All tablets will be crushed by the site clinical trial pharmacist according to the randomisation schedule and placed in a clear, labelled vial for dispensing. Each vial will be numbered according to the pre-determined randomisation code and labelled according to the prescription from the investigator. All vials for a treatment (famotidine) and the placebo will look identical in colour and texture to preserve the blinding irrespective of the contents. Medication will be administered by nursing staff each day, mixing the contents of one vial per day with a thick fluid such as yoghurt or apple puree.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The REDCap (Research Electronic Data Capture) randomisation tool will be used to facilitate randomisation. Participants will be stratified according to the presence or absence of an NGT. Treatment for each participant will then be allocated in a 1:1 ratio as per their level of stratification. Block randomisation will ensure even allocation to each code.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
This study is comprised of a total of 20 patients, with the primary focus on feasibility within this patient population. Due to the low patient target number and primary outcome measure, there will be no inferential statistical analyses for the primary or secondary outcome measures. All results will be descriptive and exploratory in nature.

Recruitment
Recruitment status
Stopped early
Data analysis
Data collected is being analysed
Reason for early stopping/withdrawal
Participant recruitment difficulties
Date of first participant enrolment
Anticipated
1/11/2021
Actual
15/02/2022
Date of last participant enrolment
Anticipated
Actual
1/12/2022
Date of last data collection
Anticipated
Actual
10/12/2022
Sample size
Target
20
Accrual to date
Final
4
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 17263 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
Recruitment hospital [2] 17264 0
Liverpool Hospital - Liverpool
Recruitment hospital [3] 17265 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [4] 17423 0
Calvary Health Care Sydney Ltd - Kogarah
Recruitment hospital [5] 19886 0
Braeside Hospital - Prairiewood
Recruitment hospital [6] 23548 0
Camden Hospital - Camden
Recruitment postcode(s) [1] 30976 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 30977 0
2170 - Liverpool
Recruitment postcode(s) [3] 30978 0
3084 - Heidelberg
Recruitment postcode(s) [4] 31151 0
2217 - Kogarah
Recruitment postcode(s) [5] 34587 0
2176 - Prairiewood
Recruitment postcode(s) [6] 38970 0
2570 - Camden

Funding & Sponsors
Funding source category [1] 306469 0
Other
Name [1] 306469 0
SPHERE
Country [1] 306469 0
Australia
Primary sponsor type
University
Name
University of Technology Sydney
Address
15 Broadway
Ultimo
NSW 2007
Country
Australia
Secondary sponsor category [1] 306992 0
None
Name [1] 306992 0
Address [1] 306992 0
Country [1] 306992 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 306677 0
South Western Sydney Local Health District Human Research Ethics Committee
Ethics committee address [1] 306677 0
Research Directorate
Locked Bag 7103
LIVERPOOL BC NSW 1871
Ethics committee country [1] 306677 0
Australia
Date submitted for ethics approval [1] 306677 0
29/01/2021
Approval date [1] 306677 0
11/03/2021
Ethics approval number [1] 306677 0

Summary
Brief summary
The aim of this study is to determine whether it is feasible to conduct a study of crushed oral dexamethasone, at a dose of at least 8 mg daily, either with or without daily crushed oral famotidine in the management of inoperable bowel obstruction.

Who is it for?
You may be eligible for this study if you are aged 18 years or older, have advanced cancer, and have a clinically confirmed inoperable bowel obstruction at any level with vomiting that requires a hospital admission or a change in clinical care.

Study details
Participants will be randomised (i.e. allocated by chance) to receive 5 days of either 40mg per day of famotidine or placebo as a crushed oral tablet. All participants will also receive a single daily dose of 8mg of dexamethasone for 5 days and intravenous or subcutaneous fluids at 10-20ml/kg/24 hours, as part of standard care. Participants will be assessed daily for the duration of treatment to monitor safety and tolerability, where the study team will visit each day and assess any side effects and improvement. Participants will also complete a number of questionnaires on the last day of treatment, as well as weekly for 4 weeks post-treatment completion. These questionnaires will involve answering questions regarding general well-being and quality of life, vomiting episodes, pain, nausea, side effects, medication use, and use of rescue pain medications. Analysis for cost-effectiveness of the intervention will also occur.

It is hoped that this study will help clinicians to further understand the management of of inoperable malignant bowel obstruction.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 104638 0
Prof Meera Agar
Address 104638 0
Ingham Institute of Applied Medical Research,
1 Campbell Street,
Liverpool NSW 2170
Country 104638 0
Australia
Phone 104638 0
+61 02 9514 5967
Fax 104638 0
Email 104638 0
[email protected]
Contact person for public queries
Name 104639 0
Meera Agar
Address 104639 0
Ingham Institute of Applied Medical Research,
1 Campbell Street,
Liverpool NSW 2170
Country 104639 0
Australia
Phone 104639 0
+61 02 9514 5967
Fax 104639 0
Email 104639 0
[email protected]
Contact person for scientific queries
Name 104640 0
Meera Agar
Address 104640 0
Ingham Institute of Applied Medical Research,
1 Campbell Street,
Liverpool NSW 2170
Country 104640 0
Australia
Phone 104640 0
+61 02 9514 5967
Fax 104640 0
Email 104640 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
This study aims to assess feasibility of methods and study design to inform a phase 3 design and hence data will not be shared.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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No documents have been uploaded by study researchers.

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