Gallbladder CancerPhase 2NCT04362449
Comparing the Current Hydration Regimen for the ABC02 Chemotherapy Regimen Versus a Shorter Hydration
A Phase 2 study testing Shortened hydration time and dispensary of Akynzeo in people with Gallbladder Cancer, run by Imperial College Healthcare NHS Trust at 1 site in United Kingdom.
Trial summary
This is an open label study for any patients with a bile duct cancer or gallbladder cancer, who will be treated with gemcitabine and cisplatin chemotherapy (the ABC02 regime). Patients recruited onto this study will have a reduction of their hydration time and be given Akynzeo as an anti-sickness drug, to assess… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gallbladder Cancer
- What is being tested?
- Shortened hydration time and dispensary of Akynzeo
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 2 Jan 2019to 2 Feb 2023
- Phase
- Phase 2
- 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
- Adults with normal renal function at the start i.e. eGFR>60, Performance status 0 and 1, controlled nausea and vomiting at baseline.
- ECOG performance status 0 or 1
- Diagnosed with either cholangio carcinoma, gallbladder cancer, pulmonary cancer or pancreatic cancer. Patients should be able to tolerate 1 litre of oral fluid pre-treatment and post treatment.
- Decision to treat with the gemcitabine and cisplatin used in the ABC02 trial.
Who cannot join
- Participants under the age of 18 years old with Chronic renal impairment. The standard exclusion of renal impairment for cisplatin implies that this study would not be offered to patients, who can't be safely offered cisplatin
- Uncontrolled nausea or vomiting
- Unable to drink 1 litre of fluid
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site, 1 recruiting
- Recruiting
Imperial College Healthcare NHS Trust
London, W12 0HS
Harpreet Wasan, MD, 0208 383 3089
Harpreet Wasan, MD
About this study
Official title: A Prospective Study of Tolerance Comparing the Current Hydration Regimen for the ABC02 Chemotherapy Regimen Versus a Shorter Hydration
This is an open label study for any patients with a bile duct cancer or gallbladder cancer, who will be treated with gemcitabine and cisplatin chemotherapy (the ABC02 regime). Patients recruited onto this study will have a reduction of their hydration time and be given Akynzeo as an anti-sickness drug, to assess tolerability compared to the current standard of care. The aim of this research is to assess the tolerability of a shorter hydration time, which may improve patient satisfaction as they would then spend less time in hospital having chemotherapy, saving both time and money for the institutions also.
Read the detailed description
The ABC02 treatment regime was established in 2010 following publication in the New England Journal of Medicine and has since become the standard of care treatment of bile duct cancers otherwise known as cholangiocarcinomas, as well as gallbladder cancer. The treatment consists of gemcitabine and cisplatin given synergistically. This combination has been shown to yield an overall survival advantage of 3.6 months compared to when gemcitabine is given on its own, with additional improvements in performance status and tumour control in patients.
Currently, the ABC02 regime includes a long hydration schedule based on previous use of high doses of cisplatin and perhaps historically the lack of efficacious antiemetics. Cisplatin is often associated with severe nausea and vomiting that lead to dehydration. In fact, cisplatin is a direct nephrotoxin, owing to its pro-inflammatory action in the kidneys and being able to cause immediate vasoconstriction of renal microvasculature on administration, and this coupled with its effect to induce dehydration due to nausea and vomiting, prevented the inclusion of cisplatin into many combinational regimens. 50% of patients in initial studies were found to suffer from nephrotoxicity on cisplatin and thus the administration of intravenous saline to combat this effect by inducing diuresis has also been standard of care when giving cisplatin chemotherapy. However, it is still not known what the optimal hydration solution and procedure are as there are no studies comparing either of these factors.
Akynzeo is a mixture of both a 5HT3 blocker palonosetron and a neurokinin 1 inhibitor netupitant. Together the drugs are able to combat nausea and vomiting during the acute phase and delayed phase after chemotherapy. The introduction of 5HT3 blockers cut the incidence of acute nausea and vomiting in chemotherapy patients considerably, but in fear of the historical nephrotoxicity, copious volumes of IV saline remains part of the regime. This entire procedure takes 8 hours for delivery and risks fluid overload often requiring diuretic management.
For reference: gemcitabine is an antimetabolite and works by imitating a pyrimidine and replacing the cytidine in nucleic acid during DNA replication. By doing so, gemcitabine halts tumour growth as actual nucleosides cannot be attached to this faulty nucleoside and this results in apoptosis. Cisplatin on the other hand is an alkylating agent and kills cancer cells by binding to DNA and interfering with its repair mechanism; upon binding to DNA it further attracts other DNA repair proteins to irreversibly bind to the structure distorting its shape and inducing apoptosis.
- Conditions
- Gallbladder Cancer
- Being tested
- Shortened hydration time and dispensary of Akynzeo, Standard of care
- Medical subject headings
- Gallbladder Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Shortened hydration time and dispensary of AkynzeoCombination product
Hydration is reduced to 1 hour and 40 minutes and Akynzeo is administered as an oral drug instead of Ondansetron being given as an IV before chemotherapy.
Standard of careCombination product
Hydration remains at around 6 hours and 30 minutes due to no oral fluids being consumed prior to treatment and normal saline being administered for 90 minutes before cisplatin and then for 2 hours after cisplatin and before gemcitabine administration
| Study group | Role | What they receive |
|---|---|---|
| Shortened hydration time with dispensary of Akynzeo | Experimental | ABC-02 regime - gemcitabine and cisplatin with a shortened hydration time and administration of a newer antiemetic Receives: Combination Product: Shortened hydration time and dispensary of Akynzeo |
| Standard of care | Active comparator | ABC-02 regime - gemcitabine and cisplatin with currently approved hydration time and administration of the current choice of antiemetic Receives: Combination Product: Standard of care |
What is being measured
The primary outcome is the main question the study is designed to answer.
Nausea according to the Common Terminology Criteria for Adverse Events (CTCAE) V4.03
To compare the proportion of patients who experience CTCAE V3.0 grade 3 or 4 nausea (using a shortened hydration protocol and a modern antiemetic regimen) with those who are in the ABC02 trial arm which used a longer hydration procedure and a standard antiemetic regimen
Measured: Throughout study completion, up to 1 year
Secondary outcomes (6)
Renal function of patients
To compare proportion of patients who experience CTCAE V3.0 grade 3 or 4 impaired renal function
Measured: Throughout study completion, up to 1 year
Number of patients who have a complete response
To compare proportion of patients who have a complete response i.e. no nausea and vomiting recorded as a toxicity
Measured: Throughout study completion, up to 1 year
Number of patients with renal dysfunction
To compare the proportion of patients who experience renal dysfunction (a deterioration of calculated GFR of below 60)
Measured: Throughout study completion, up to 1 year
Number of cases of chemotherapy induced emesis
To determine the incidence of early and delayed chemotherapy induced emesis using the MAT antiemesis tool
Measured: Throughout study completion, up to 1 year
Nocturia experienced by patients
To determine the incidence of nocturia in the first night after chemotherapy
Measured: Throughout study completion, up to 1 year
Health economics in the context of duration of hospital attendance
Measuring the length of hospital visit (time in to time out) for each patient per treatment visit and comparing the difference between arms
Measured: Throughout study completion, up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Apr 2020
- Study start2 Jan 2019
- Primary completion2 Feb 2023 (estimated)
- Study completion2 Feb 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Gallbladder CancerStudies of the same condition, open and under way.
- 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
- Supportive care
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Imperial College Healthcare NHS Trust
- Sponsor type
- University, hospital or other
- Collaborators
- Chugai Pharma UK Limited
- Responsible party
- Sponsor
- Investigators
- Harpreet Wasan, MD, Principal investigator, Gastrointestinal Clinical Research Lead and Consultant Oncologist
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04362449
- Sponsor's protocol ID
- 214262
- Status last verified
- Jul 2022
- First submitted
- 17 Apr 2020
- Last updated
- 15 Jul 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 15 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective Study of Tolerance Comparing the Current Hydration Regimen for the ABC02 Chemotherapy Regimen Versus a Shorter Hydration
- ClinicalTrials.gov ID
- NCT04362449
- Acronym / sponsor ID
- 214262
- Conditions
- Gallbladder Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Imperial College Healthcare NHS TrustUniversity, hospital or other
- Collaborators
- Chugai Pharma UK Limited
- Study start
- 2 Jan 2019 (actual)
- Primary completion
- 2 Feb 2023 (estimated)
- Study completion
- 2 Feb 2023 (estimated)
- First posted
- 27 Apr 2020 (actual)
- 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 is an open label study for any patients with a bile duct cancer or gallbladder cancer, who will be treated with gemcitabine and cisplatin chemotherapy (the ABC02 regime). Patients recruited onto this study will have a reduction of their hydration time and be given Akynzeo as an anti-sickness drug, to assess tolerability compared to the current standard of care. The aim of this research is to assess the tolerability of a shorter hydration time, which may improve patient satisfaction as they would then spend less time in hospital having chemotherapy, saving both time and money for the institutions also.
Detailed description
The ABC02 treatment regime was established in 2010 following publication in the New England Journal of Medicine and has since become the standard of care treatment of bile duct cancers otherwise known as cholangiocarcinomas, as well as gallbladder cancer. The treatment consists of gemcitabine and cisplatin given synergistically. This combination has been shown to yield an overall survival advantage of 3.6 months compared to when gemcitabine is given on its own, with additional improvements in performance status and tumour control in patients.
Currently, the ABC02 regime includes a long hydration schedule based on previous use of high doses of cisplatin and perhaps historically the lack of efficacious antiemetics. Cisplatin is often associated with severe nausea and vomiting that lead to dehydration. In fact, cisplatin is a direct nephrotoxin, owing to its pro-inflammatory action in the kidneys and being able to cause immediate vasoconstriction of renal microvasculature on administration, and this coupled with its effect to induce dehydration due to nausea and vomiting, prevented the inclusion of cisplatin into many combinational regimens. 50% of patients in initial studies were found to suffer from nephrotoxicity on cisplatin and thus the administration of intravenous saline to combat this effect by inducing diuresis has also been standard of care when giving cisplatin chemotherapy. However, it is still not known what the optimal hydration solution and procedure are as there are no studies comparing either of these factors.
Akynzeo is a mixture of both a 5HT3 blocker palonosetron and a neurokinin 1 inhibitor netupitant. Together the drugs are able to combat nausea and vomiting during the acute phase and delayed phase after chemotherapy. The introduction of 5HT3 blockers cut the incidence of acute nausea and vomiting in chemotherapy patients considerably, but in fear of the historical nephrotoxicity, copious volumes of IV saline remains part of the regime. This entire procedure takes 8 hours for delivery and risks fluid overload often requiring diuretic management.
For reference: gemcitabine is an antimetabolite and works by imitating a pyrimidine and replacing the cytidine in nucleic acid during DNA replication. By doing so, gemcitabine halts tumour growth as actual nucleosides cannot be attached to this faulty nucleoside and this results in apoptosis. Cisplatin on the other hand is an alkylating agent and kills cancer cells by binding to DNA and interfering with its repair mechanism; upon binding to DNA it further attracts other DNA repair proteins to irreversibly bind to the structure distorting its shape and inducing apoptosis.
Study design
- Primary purpose
- Supportive care
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Shortened hydration time with dispensary of Akynzeo | Experimental | Combination Product: Shortened hydration time and dispensary of AkynzeoABC-02 regime - gemcitabine and cisplatin with a shortened hydration time and administration of a newer antiemetic |
| Standard of care | Active comparator | Combination Product: Standard of careABC-02 regime - gemcitabine and cisplatin with currently approved hydration time and administration of the current choice of antiemetic |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Adults with normal renal function at the start i.e. eGFR>60, Performance status 0 and 1, controlled nausea and vomiting at baseline.
- ECOG performance status 0 or 1
- Diagnosed with either cholangio carcinoma, gallbladder cancer, pulmonary cancer or pancreatic cancer. Patients should be able to tolerate 1 litre of oral fluid pre-treatment and post treatment.
- Decision to treat with the gemcitabine and cisplatin used in the ABC02 trial.
Key exclusion criteria (3 listed)
- Participants under the age of 18 years old with Chronic renal impairment. The standard exclusion of renal impairment for cisplatin implies that this study would not be offered to patients, who can't be safely offered cisplatin
- Uncontrolled nausea or vomiting
- Unable to drink 1 litre of fluid
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 |
|---|---|---|
| Shortened hydration time and dispensary of AkynzeoHydration is reduced to 1 hour and 40 minutes and Akynzeo is administered as an oral drug instead of Ondansetron being given as an IV before chemotherapy. | Combination product | Shortened hydration time with dispensary of Akynzeo |
| Standard of careHydration remains at around 6 hours and 30 minutes due to no oral fluids being consumed prior to treatment and normal saline being administered for 90 minutes before cisplatin and then for 2 hours after cisplatin and before gemcitabine administration | Combination product | Standard of care |
Primary outcome
Nausea according to the Common Terminology Criteria for Adverse Events (CTCAE) V4.03
Time frame: Throughout study completion, up to 1 year
To compare the proportion of patients who experience CTCAE V3.0 grade 3 or 4 nausea (using a shortened hydration protocol and a modern antiemetic regimen) with those who are in the ABC02 trial arm which used a longer hydration procedure and a standard antiemetic regimen
6 secondary outcomes
Renal function of patients
Time frame: Throughout study completion, up to 1 year
Number of patients who have a complete response
Time frame: Throughout study completion, up to 1 year
Number of patients with renal dysfunction
Time frame: Throughout study completion, up to 1 year
Number of cases of chemotherapy induced emesis
Time frame: Throughout study completion, up to 1 year
Nocturia experienced by patients
Time frame: Throughout study completion, up to 1 year
Health economics in the context of duration of hospital attendance
Time frame: Throughout study completion, up to 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jul 2022.
- Individual participant dataSharing planned: Undecided
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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.
Harpreet Wasan, MD principal investigator
Gastrointestinal Clinical Research Lead and Consultant Oncologist
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 Shortened hydration time and dispensary of Akynzeo in people with Gallbladder Cancer, run by Imperial College Healthcare NHS Trust at 1 site in United Kingdom.
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 4 inclusion and 3 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: status not confirmed, as of the sponsor's last update on 15 Jul 2022. 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 Kingdom. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Harpreet Wasan, MD (0208 383 3089, h.wasan@imperial.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Nausea according to the Common Terminology Criteria for Adverse Events (CTCAE) V4.03 (time frame: Throughout study completion, up to 1 year). 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 15 Jul 2022.