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Trial registered on ANZCTR


Registration number
ACTRN12618000232235
Ethics application status
Approved
Date submitted
7/02/2018
Date registered
13/02/2018
Date last updated
6/08/2019
Date data sharing statement initially provided
6/08/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Ibudilast for the prevention of nerve symptoms caused by oxalipatin chemotherapy, in patients with metastatic gastrointestinal cancer
Scientific title
A pilot study evaluating the impact of ibudilast on prevention of chemotherapy-induced neurotoxicity and evaluating pharmacokinetics in metastatic gastro-intestinal cancer patients receiving oxaliplatin
Secondary ID [1] 293968 0
Nil known
Universal Trial Number (UTN)
U1111-1209-0075
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute neurotoxicity
 306479 0
Chemotherapy induced peripheral neuropathy (CIPN) 306480 0
Metastatic gastrointestinal cancer 306481 0
Condition category
Condition code
Cancer 305576 305576 0 0
Bowel - Back passage (rectum) or large bowel (colon)
Cancer 305577 305577 0 0
Bowel - Anal
Neurological 305578 305578 0 0
Other neurological disorders
Cancer 305629 305629 0 0
Bowel - Small bowel (duodenum and ileum)
Cancer 305630 305630 0 0
Stomach
Cancer 305631 305631 0 0
Pancreatic
Cancer 305632 305632 0 0
Liver

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Ibudilast is a non-selective phosphodiesterase (PDE) inhibitor with anti-inflammatory properties which has shown to improve acute neurotoxicity in animal models. The study intervention will be oral ibudilast 30mg twice daily for the duration of one cycle, named Cycle B. The duration of the cycle is 2 weeks for patients receiving infusional fluorouracil with oxaliplatin (FOLFOX) and 3 weeks for patients receiving oral capecitabine with oxaliplatin (CapeOx). There is no washout period. Drug tablet return at the end of the cycle and weekly phone contact will be used to monitor adherence to the intervention.
Intervention code [1] 300236 0
Treatment: Drugs
Intervention code [2] 300237 0
Prevention
Comparator / control treatment
The study control is a cycle, named Cycle A, is the patient's usual chemotherapy without the addition of oral ibudilast (FOLFOX or CapeOx).
Control group
Active

Outcomes
Primary outcome [1] 304702 0
Proportion of patients developing neurotoxicity > Grade 2 following their chemotherapy cycle as measured by the oxaliplatin-specific neurotoxicity scale (OSNS) modified. Compared between day 3 of cycle A vs Day 3 of cycle B.
Timepoint [1] 304702 0
Day 3 of chemotherapy cycles
Secondary outcome [1] 342843 0
Daily diary acute neuropathy rating scale - questionnaire specifically designed for the study based on the National Cancer Institute (NCI) Common Criteria for Adverse Events (CTCAE)
Timepoint [1] 342843 0
Daily for each of the study cycles of chemotherapy
Secondary outcome [2] 342844 0
European Organisation for Research and Treatment of Cancer (EORTC)-Quality of life questionnaire (QLQ)-CIPN
Timepoint [2] 342844 0
Baseline and end of study cycles
Secondary outcome [3] 342845 0
Total neuropathy score - composite of symptoms, reflexes, pinprick, vibration
Timepoint [3] 342845 0
Baseline, Day 3 of study cycles, end of study cycles, 3 months post baseline
Secondary outcome [4] 342846 0
Difference in Grade of neuropathy between cycles A and B using NCI-CTCAE neuropathy sensory subscale
Timepoint [4] 342846 0
Baseline, Day 3 and end of study cycles, 3 months post baseline
Secondary outcome [5] 342847 0
Oxaliplatin dose reduction or delay, assessed by review of medical records at end of cycles A and B
Timepoint [5] 342847 0
End of study cycles, 3 months post baseline
Secondary outcome [6] 342848 0
Detection of 10g Von Frey filament on ball of foot: yes/no assessed by clinical observation.
Timepoint [6] 342848 0
Day 3 and end of study cycle, 3 months post baseline
Secondary outcome [7] 342849 0
Adverse events as measured by NCI-CTCAE, for example, anaemia, neutropenia, thrombocytopenia, nausea.
Timepoint [7] 342849 0
End of study cycles A and B and 3 months post baseline assessment
Secondary outcome [8] 342850 0
Plasma levels of platinum compared at matched time points between cycle A and B
Timepoint [8] 342850 0
Baseline, Day 1 of chemotherapy, Day 3 of chemotherapy and end of cycle sampling
Secondary outcome [9] 342995 0
Plasma levels of fluorouracil compared at matched time points between cycle A and B
Timepoint [9] 342995 0
Baseline, Day 1 of chemotherapy, Day 3 of chemotherapy, end of cycle
Secondary outcome [10] 343075 0
Pain threshold assessed by cold pressor task - time to withdrawal of hand.
Timepoint [10] 343075 0
Baseline, Day 1 of chemotherapy, Day 3 of chemotherapy, end of cycle

Eligibility
Key inclusion criteria
1. Diagnosis of metastatic upper gastrointestinal or colorectal cancer
2. Aged > 18 years
3. Patient has received at least one prior cycle of FOLFOX or CapeOx
4. Planned to receive at least two further cycles of the same chemotherapy
5. Speak and read sufficientEnglish to answer the questionnaires
6. Normal renal function with glomerular filtration rate >90mL/min
7. Give written informed consent
8. Patient must be accessible for treatment and follow up. Investigators must assure themselves the patients will be available for complete documentation of the treatment adverse events and follow up.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. ECOG Performance Status of less than or equal to 2
2. Any major active psychiatric illness, dementia, or alcohol abuse that in the opinion of the principal investigator may interfere with their ability to complete neurotoxicity assessments
3. Any contraindication to taking ibudilast, including uncontrolled nausea or vomiting with chemotherapy
4. Inability to swallow capsules

Study design
Purpose of the study
Prevention
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Not applicable as non randomised trial
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Not applicable as non randomised trial
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Prospective, open-label, sequential crossover pilot study, with safety, efficacy and pharmacokinetics endpoints.
Phase
Phase 1
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
This trial is a pilot study, the results of which can provide rationale to perform a larger randomised control trial if positive. We based our sample size calculations assuming almost all patients receiving oxaliplatin develop acute neurotoxicity by cycle 2 and 50% develop CIPN by 3 months. We would consider ibudilast promising for further evaluation if in 20 patients, less than 10 patients develop acute neurotoxicity (as measured by OSNS).

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
2/04/2018
Actual
8/05/2018
Date of last participant enrolment
Anticipated
30/11/2018
Actual
16/01/2019
Date of last data collection
Anticipated
28/02/2019
Actual
16/04/2019
Sample size
Target
20
Accrual to date
Final
16
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 9956 0
Concord Repatriation Hospital - Concord
Recruitment postcode(s) [1] 18786 0
2139 - Concord

Funding & Sponsors
Funding source category [1] 298600 0
Hospital
Name [1] 298600 0
Concord Cancer Centre
Country [1] 298600 0
Australia
Primary sponsor type
Hospital
Name
Concord Cancer Centre
Address
Hospital Road Concord NSW 2139
Country
Australia
Secondary sponsor category [1] 297760 0
None
Name [1] 297760 0
Address [1] 297760 0
Country [1] 297760 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299562 0
Human Research Ethics Comitte - Concord Repatriation General Hospital (CGRH)
Ethics committee address [1] 299562 0
Hospital Rd
Concord NSW 2139
Ethics committee country [1] 299562 0
Australia
Date submitted for ethics approval [1] 299562 0
29/01/2018
Approval date [1] 299562 0
16/03/2018
Ethics approval number [1] 299562 0

Summary
Brief summary
This study aims to determine if ibudilast, an anti-inflammatory drug, can prevent acute neurotoxicity and chemotherapy induced peripheral neuropathy.

Who is it for?
You may be eligible if you are over 18 years old, have been diagnosed with metastatic gastrointestinal cancer and have at least two cycles of chemotherapy with oxaliplatin planned.

Study details
Participants will be required to take the study drug, twice a day, for one cycle of chemotherapy treatment (2-3 weeks depending on the length of the chemotherapy cycle). Participants will also be observed for one cycle of chemotherapy treatment.

Participants will also need to complete questionnaires, take blood tests and complete a physical assessment with a clinician. This will occur at the beginning of the study, during the chemotherapy cycles and one more time 3 months later.

This study will help to inform research into minimising side effects for patients while undergoing chemotherapy.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 80846 0
A/Prof Janette Vardy
Address 80846 0
Concord Cancer Centre
Hospital Rd, Concord NSW 2139
Country 80846 0
Australia
Phone 80846 0
+61 02 97676354
Fax 80846 0
+61 02 97675764
Email 80846 0
[email protected]
Contact person for public queries
Name 80847 0
Christina Teng
Address 80847 0
Concord Cancer Centre
Hospital Rd, Concord NSW 2139
Country 80847 0
Australia
Phone 80847 0
+61 02 97676354
Fax 80847 0
+61 02 97675764
Email 80847 0
[email protected]
Contact person for scientific queries
Name 80848 0
Christina Teng
Address 80848 0
Concord Cancer Centre
Hospital Rd, Concord NSW 2139
Country 80848 0
Australia
Phone 80848 0
+61 02 97676354
Fax 80848 0
+61 02 97675764
Email 80848 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De identified patient reported outcome and toxicity data on request and by agreement of investigators.
When will data be available (start and end dates)?
Oct-Dec 2019
Available to whom?
Case by case basis at discretion of investigators
Available for what types of analyses?
To achieve aims as stated in protocol
How or where can data be obtained?
Subject to approval by Principal investigator


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.