Biliary Tract CancerPhase 1ABC-08NCT02351765
ABC-08: Phase Ib Trial of Acelarin in Combination With Cisplatin in Locally Advanced/ Metastatic Biliary Tract Cancers
A Phase 1 study testing Acelarin and Cisplatin in people with Biliary Tract Cancer and Gallbladder Cancer, run by The Christie NHS Foundation Trust at 5 sites in United Kingdom.
Trial summary
The purpose of this study is to determine the recommended phase II dose, and to assess the safety of acelarin in combination with cisplatin in patients with locally advanced/ metastatic biliary tract cancers. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Biliary Tract Cancer, Gallbladder Cancer, Cholangiocarcinoma
- What is being tested?
- Acelarin and Cisplatin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 5 sitesUnited Kingdom
- Study dates
- Jan 2016to Mar 2019
- 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
- Histologically/cytologically verified, non-resectable or recurrent/metastatic cholangiocarcinoma, gallbladder or ampullary carcinoma.
- No prior systemic therapy allowed for advanced biliary cancer. Prior low dose chemotherapy used with or without radiotherapy in the adjuvant setting is allowed if completed > 6 months from enrolment. Recent palliative radiation (within 28 days prior to consent) is allowed if candidate has measurable disease outside radiation field.
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
- Age ≥ 18 years and life expectancy > 3 months.
- Adequate renal function with serum urea and serum creatinine < 1.5 times upper limit of normal (ULN) and creatinine clearance ≥ 30ml/min.
- Adequate haematological function: Hb ≥ 10g/dl, white blood count (WBC) ≥ 3.0 x 10*9/L, absolute neutrophil count (ANC) ≥ 1.5 x 10*9/L, platelet count ≥ 100,000/mm3.
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- Adequate liver function: total bilirubin < 30 μmol/L and alkaline phosphatase, along with aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≤ 5 x ULN.
- Adequate biliary drainage, with no evidence of ongoing infection.
- Women of child bearing age MUST have a negative pregnancy test prior to study entry AND be using a highly effective contraception method (combined or progestogen-only hormonal contraception, intrauterine device, intrauterine hormone-releasing system, vasectomised partner*(a) or sexual abstinence**(b)) which must be continued for 6 months after the end of study treatment, unless child bearing potential has been terminated by surgery/radical radiotherapy or infertility due to bilateral tubal occlusion.
- Male subjects must either have had a successful vasectomy (confirmed azoospermia) or they and their female partner meet the criteria above (not of childbearing potential or practicing adequate contraception [e.g. combined or progestogen-only hormonal contraception, intrauterine device, intrauterine hormone-releasing system, sexual abstinence**(b)] throughout the study period and for 6 months after the end of study treatment).
- Patients must not have a history of other malignant diseases (within the previous 5 years and there must be no evidence of recurrence), other than adequately treated non-melanotic skin cancer or in-situ carcinoma of the uterine cervix.
- Patients must have given written informed consent.
- (a) The vasectomised partner must have received medical assessment confirming surgical success.
- (b) Sexual abstinence in line with the preferred and usual lifestyle of the subject.
Who cannot join
- History of allergic reactions attributed to previous gemcitabine or cisplatin treatment.
- Documented history of allergic reactions attributed to any of the excipients used in the formulation (Kolliphor ELP; Tween 80; DMA).
- Previous treatment with Acelarin.
- Incomplete recovery from previous therapy (surgery/adjuvant therapy/radiotherapy) or unresolved biliary tree obstruction.
- Any evidence of severe or uncontrolled systemic diseases which, in the view of the investigator, makes it undesirable for the patient to participate in the trial.
- Evidence of significant clinical disorder or laboratory finding which, in the opinion of the investigator makes it undesirable for the patient to participate in the trial.
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- Any patient with a medical or psychiatric condition that impairs their ability to give informed consent.
- Any other serious uncontrolled medical conditions.
- Clinical evidence of metastatic disease to the brain.
- Any pregnant or lactating woman.
- Pre-existing hearing impairment.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United Kingdom5 sites
Beatson Oncology Centre
Glasgow
Clatterbridge Cancer Centre
Liverpool
Imperial College London
London
University College London
London
The Christie NHS Foundation Trust
Manchester
About this study
Official title: A Phase Ib, Multi-centre, Open-label Study of a First-in-class Nucleotide Analogue Acelarin (NUC-1031) in Combination With Cisplatin in Patients With Locally Advanced/Metastatic Biliary Tract Cancers
The purpose of this study is to determine the recommended phase II dose, and to assess the safety of acelarin in combination with cisplatin in patients with locally advanced/ metastatic biliary tract cancers.
Read the detailed description
Active chemotherapy drugs for the treatment of advanced biliary tract cancers (ABC) include gemcitabine, fluoropyrimidines and platinum agents. The United Kingdom (UK) National Cancer Research Network (NCRN) ABC-02 study established cisplatin and gemcitabine as the standard of care for the first-line treatment of patients with ABC and this regimen has been widely adopted in the UK and internationally. However, inherent and acquired tumour resistance limits the efficacy of gemcitabine and it is necessary to explore alternative treatments.
The study will explore the combination of acelarin, a drug designed to specifically overcome the key cancer resistance mechanisms associated with gemcitabine, with cisplatin. As this is the first time the combination of acelarin and cisplatin will be given to patients the aim of the study is to investigate the safety of the combination and to establish the recommended phase II dose of acelarin.
This is a phase Ib, single-arm, multi-centre, open-label trial. The trial design is a classic 3+3 design where patients are recruited into cohorts of 3 to 6 patients at different dose levels until the dose level for phase II is determined. Patients in each cohort will be monitored closely for safety and drug toxicity.
Secondary trial objectives will involve assessing the activity of acelarin in combination with cisplatin in terms of; progression-free survival, overall survival and response rate, as well as exploring the pharmacokinetic profile of the combination.
- Being tested
- Acelarin, Cisplatin
- Medical subject headings
- Biliary Tract Neoplasms, Gallbladder Neoplasms, Cholangiocarcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AcelarinDrug
Also called Code name: NUC-1031
First-in-class nucleotide analogue
CisplatinDrug
Also called Anatomical Therapeutic Chemical (ATC) code: L01XA01
Platinum-compound chemotherapy drug
| Study group | Role | What they receive |
|---|---|---|
| Acelarin & Cisplatin | Experimental | The maximum tolerated dose (MTD) of Acelarin in combination with 25mg/m2 Cisplatin will be determined.
The starting dose will be 625mg/m2 Acelarin which will be escalated to 725mg/m2 if the criteria for dose escalation is met (i.e. the proportion of dose limiting toxicities is acceptable as detailed in the protocol). Escalation will continue in accordance with the protocol up to a maximum of 925mg/m2. Only if the MTD is exceeded at the starting dose level (at least 2 of 3 participants or at least 2 of 6 participants have DLT at the first dose level) will there be a de-escalation to 500mg. Receives: Drug: Acelarin; Drug: Cisplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety profile of Acelarin in combination with Cisplatin, assessed by total incidence and rate of grade 3 and 4 adverse events according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)
Safety will be assessed by comparing the total incidence and rate of grade 3 and 4 adverse events that occur after initiation of therapy, according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)
Measured: Adverse events recorded from initiation of therapy until 30 day post-treatment
Maximum Tolerated Dose (MTD) of Aclerain in combination with Cisplatin
The MTD will be defined as the maximum dose level at which 0/3 patients or 1/6 patients experience dose-limiting toxicity (DLT). At any dose level, DLT in 1/3 patients will lead to expansion to 6 patients. If 2/6 patients experience DLT the preceding dose level will be declared the MTD. At the MTD up to 6 additional patients may be enrolled. If this level is well tolerated, it will be declared the recommended phase II dose (RP2D).
Measured: After 13 months of first patient included
Secondary outcomes (4)
Progression-free survival
Clinical progression assessed every six weeks, radiological progression assessed to Response Evaluation Criteria in Solid Tumors (RECIST) criteria every 12 weeks.
Measured: Evaluated by 6 weekly follow-up until 12 months after the last patient included
Overall survival
Measured: Evaluated by 6 weekly follow-up until 12 months after the last patient included
Response rate
Response will be calculated as a composite of objective response rate (ORR) by RECIST 1.1 (summation of patients with a complete or partial response [any time]).
Measured: After 12 weeks of treatment
Exploration of the pharmacokinetic profile for the combination of Acelarin with Cisplatin
Plasma and intracellular levels of acelarin, cisplatin, gemcitibine (2', 2'-difluoro 2'-deoxycytidine) (dFdC), gemcitabine monophosphate (dFdCMP), gemcitabine diphosphate (dFdCDP), gemcitabine triphosphate (dFdCTP) and difluorodeoxyuridine (dFdU) will be measured and correlated with clinical activity and safety profile.
Measured: At baseline (prior to chemotherapy administration), 30, 60 and 240 minutes following line flush at the end of acelarin administration. Cycle 1 day 1 only
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2015 (estimated)
- Study startJan 2016
- Primary completionMar 2019
- Study completionMar 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Biliary Tract 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Christie NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mairéad G McNamara, MD, Study chair, The Christie NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02351765
- Sponsor's protocol ID
- CFTSp096
- Other IDs
- 2015-000100-26, 2015
- Acronym
- ABC-08
- Status last verified
- May 2023
- First submitted
- 27 Jan 2015
- Last updated
- 17 May 2023
- Results posted
- No
- Data monitoring committee
- Yes
Publications
McNamara MG, Bridgewater J, Palmer DH, Faluyi O, Wasan H, Patel A, Ryder WD, Barber S, Gnanaranjan C, Ghazaly E, Evans TRJ, Valle JW. A Phase Ib Study of NUC-1031 in Combination with Cisplatin for the First-Line Treatment of Patients with Advanced Biliary Tract Cancer (ABC-08). Oncologist. 2021 Apr;26(4):e669-e678. doi: 10.1002/onco.13598. Epub 2020 Dec 3.
PubMed 33210382
Study at a glance
From the registry record, last updated by the sponsor on 17 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib, Multi-centre, Open-label Study of a First-in-class Nucleotide Analogue Acelarin (NUC-1031) in Combination With Cisplatin in Patients With Locally Advanced/Metastatic Biliary Tract Cancers
- ClinicalTrials.gov ID
- NCT02351765
- Acronym / sponsor ID
- ABC-08 / CFTSp096
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- The Christie NHS Foundation TrustUniversity, hospital or other
- Study start
- Jan 2016
- Primary completion
- Mar 2019 (actual)
- Study completion
- Mar 2019 (actual)
- First posted
- 30 Jan 2015 (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.
The purpose of this study is to determine the recommended phase II dose, and to assess the safety of acelarin in combination with cisplatin in patients with locally advanced/ metastatic biliary tract cancers.
Detailed description
Active chemotherapy drugs for the treatment of advanced biliary tract cancers (ABC) include gemcitabine, fluoropyrimidines and platinum agents. The United Kingdom (UK) National Cancer Research Network (NCRN) ABC-02 study established cisplatin and gemcitabine as the standard of care for the first-line treatment of patients with ABC and this regimen has been widely adopted in the UK and internationally. However, inherent and acquired tumour resistance limits the efficacy of gemcitabine and it is necessary to explore alternative treatments.
The study will explore the combination of acelarin, a drug designed to specifically overcome the key cancer resistance mechanisms associated with gemcitabine, with cisplatin. As this is the first time the combination of acelarin and cisplatin will be given to patients the aim of the study is to investigate the safety of the combination and to establish the recommended phase II dose of acelarin.
This is a phase Ib, single-arm, multi-centre, open-label trial. The trial design is a classic 3+3 design where patients are recruited into cohorts of 3 to 6 patients at different dose levels until the dose level for phase II is determined. Patients in each cohort will be monitored closely for safety and drug toxicity.
Secondary trial objectives will involve assessing the activity of acelarin in combination with cisplatin in terms of; progression-free survival, overall survival and response rate, as well as exploring the pharmacokinetic profile of the combination.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Acelarin & Cisplatin | Experimental | Drug: Acelarin, Drug: CisplatinThe maximum tolerated dose (MTD) of Acelarin in combination with 25mg/m2 Cisplatin will be determined. The starting dose will be 625mg/m2 Acelarin which will be escalated to 725mg/m2 if the criteria for dose escalation is met (i.e. the proportion of dose limiting toxicities is acceptable as detailed in the protocol). Escalation will continue in accordance with the protocol up to a maximum of 925mg/m2. Only if the MTD is exceeded at the starting dose level (at least 2 of 3 participants or at least 2 of 6 participants have DLT at the first dose level) will there be a de-escalation to 500mg. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Histologically/cytologically verified, non-resectable or recurrent/metastatic cholangiocarcinoma, gallbladder or ampullary carcinoma.
- No prior systemic therapy allowed for advanced biliary cancer. Prior low dose chemotherapy used with or without radiotherapy in the adjuvant setting is allowed if completed > 6 months from enrolment. Recent palliative radiation (within 28 days prior to consent) is allowed if candidate has measurable disease outside radiation field.
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
- Age ≥ 18 years and life expectancy > 3 months.
- Adequate renal function with serum urea and serum creatinine < 1.5 times upper limit of normal (ULN) and creatinine clearance ≥ 30ml/min.
Key exclusion criteria (11 listed)
- History of allergic reactions attributed to previous gemcitabine or cisplatin treatment.
- Documented history of allergic reactions attributed to any of the excipients used in the formulation (Kolliphor ELP; Tween 80; DMA).
- Previous treatment with Acelarin.
- Incomplete recovery from previous therapy (surgery/adjuvant therapy/radiotherapy) or unresolved biliary tree obstruction.
- Any evidence of severe or uncontrolled systemic diseases which, in the view of the investigator, makes it undesirable for the patient to participate in the trial.
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 |
|---|---|---|
| AcelarinAlso: Code name: NUC-1031First-in-class nucleotide analogue | Drug | Acelarin & Cisplatin |
| CisplatinAlso: Anatomical Therapeutic Chemical (ATC) code: L01XA01Platinum-compound chemotherapy drug | Drug | Acelarin & Cisplatin |
Primary outcome
Safety profile of Acelarin in combination with Cisplatin, assessed by total incidence and rate of grade 3 and 4 adverse events according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)
Time frame: Adverse events recorded from initiation of therapy until 30 day post-treatment
Safety will be assessed by comparing the total incidence and rate of grade 3 and 4 adverse events that occur after initiation of therapy, according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)
Maximum Tolerated Dose (MTD) of Aclerain in combination with Cisplatin
Time frame: After 13 months of first patient included
The MTD will be defined as the maximum dose level at which 0/3 patients or 1/6 patients experience dose-limiting toxicity (DLT). At any dose level, DLT in 1/3 patients will lead to expansion to 6 patients. If 2/6 patients experience DLT the preceding dose level will be declared the MTD. At the MTD up to 6 additional patients may be enrolled. If this level is well tolerated, it will be declared the recommended phase II dose (RP2D).
4 secondary outcomes
Progression-free survival
Time frame: Evaluated by 6 weekly follow-up until 12 months after the last patient included
Overall survival
Time frame: Evaluated by 6 weekly follow-up until 12 months after the last patient included
Response rate
Time frame: After 12 weeks of treatment
Exploration of the pharmacokinetic profile for the combination of Acelarin with Cisplatin
Time frame: At baseline (prior to chemotherapy administration), 30, 60 and 240 minutes following line flush at the end of acelarin administration. Cycle 1 day 1 only
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 17 May 2023.
- Derived from this study: PubMed 33210382McNamara MG, Bridgewater J, Palmer DH, Faluyi O, Wasan H, Patel A, Ryder WD, Barber S, Gnanaranjan C, Ghazaly E, Evans TRJ, Valle JW. A Phase Ib Study of NUC-1031 in Combination with Cisplatin for the First-Line Treatment of Patients with Advanced Biliary Tract Cancer (ABC-08). Oncologist. 2021 Apr;26(4):e669-e678. doi: 10.1002/onco.13598. Epub 2020 Dec 3.
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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.
Mairéad G McNamara, MD study chair
The Christie NHS Foundation Trust
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Acelarin and Cisplatin in people with Biliary Tract Cancer and Gallbladder Cancer, run by The Christie NHS Foundation Trust at 5 sites 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 14 inclusion and 11 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 17 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites 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 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?
Safety profile of Acelarin in combination with Cisplatin, assessed by total incidence and rate of grade 3 and 4 adverse events according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) (time frame: Adverse events recorded from initiation of therapy until 30 day post-treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02351765, which also lists 1 linked publication.
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 17 May 2023.