Biliary Tract NeoplasmsPhase 1ABC-04NCT01242605
ABC-04 a Study of Cisplatin, Gemcitabine and Selumetinib in Patients With Advanced Biliary Tract Cancer
A Phase 1 study testing selumetinib, gemcitabine and cisplatin in people with Biliary Tract Neoplasms and Cholangiocarcinoma, run by University College, London at 3 sites in United Kingdom.
Trial summary
The objective of this study is to establish the recommended dose of selumetinib, a novel MEK inhibitor for use in combination with gemcitabine and cisplatin. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Biliary Tract Neoplasms, Cholangiocarcinoma, Gallbladder Neoplasms
- What is being tested?
- selumetinib, gemcitabine and cisplatin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 3 sitesUnited Kingdom
- Study dates
- Feb 2012to May 2016
- 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
- A histopathological or cytological diagnosis of non-resectable, recurrent or metastatic biliary tract (intra- or extra-hepatic), gallbladder or ampullary carcinoma
- ECOG performance status 0, 1, or 2
- Age ≥ 18
- Estimated life expectancy > 3 months
- Adequate haematological function:
- Haemoglobin 9g/dL (prior transfusions for patients with low haemoglobin are allowed)
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- WBC >/= 3.0 x 10*9/L
- Absolute neutrophil count (ANC) >/= 1.5 x 10*9/L
- Platelet count >/= 100 x 10*9/L
- Adequate liver function:
- Total bilirubin ≤1.5 x upper limit of normal (ULN) OR ≤ 3.0 x upper limit of normal (ULN) if stable for a duration of two weeks
- ALT and/or AST \& alkaline phosphatase ≤ 5 x ULN
- Adequate renal function:
- Serum urea and serum creatinine < 1.5 times ULN
- Calculated GFR >/= 45 mL/min. If the calculated GFR is below 45ml/min, isotope EDTA confirmation of adequate renal function is required
- Capable of giving written informed consent
- Prior therapy is allowed (provided there has been a full recovery):
- Surgery (non-curative operation), must have evidence on nonresectable disaes progression prior to trial entry
- Radiotherapy, must have clear evidence of disease progression prior to inclusion
- Prior adjuvant chemotherapy is allowed provided neither gemcitabine nor cisplation were used and treatment was completed 28 days prior to trial entry.
Who cannot join
- Any prior exposure to MEK, Ras, or Raf inhibitors
- Cardiac conditions as follows:
- Uncontrolled hypertension (BP ≥150/95 despite optimal therapy)
- Heart failure (NYHA Class II or above)
- Prior or current cardiomyopathy
- Baseline LVEF ≤50%
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- Atrial fibrillation with heart rate >100 bpm
- Unstable ischaemic heart disease (MI within 6 months prior to starting treatment, or angina requiring use of nitrates more than once weekly).
- Incomplete recovery from previous surgery.
- Patients undergoing current treatment with curative intent.
- History of prior malignancy that could interfere with the response evaluation (exceptions include in-situ carcinoma of the cervix treated by cone-biopsy/resection, non-metastatic basal and/or squamous cell carcinomas of the skin, any early stage (stage I) malignancy adequately resected for cure greater than 5 years previously).
- Any evidence of severe or uncontrolled systemic diseases or laboratory finding that in the view of the investigator makes it undesirable for the patient to participate in the trial.
- Any psychiatric or other disorder (e.g brain metastases) likely to impact on informed consent.
- Pregnancy or breast-feeding. Women of child-bearing potential should must have a negative pregnancy test prior to study entry AND be using an adequate contraception method, which must be continued for 3 months after completion of chemotherapy
- NB. Whilst not excluded, patients with significant impaired hearing must be made aware of potential ototoxicity and may choose not to be included. If included, baseline audiograms are recommended and should be followed by repeat audiograms prior to cycle 2.
Trial locations and contacts
3 sites in 1 country.
United Kingdom3 sites
Hammersmith Hospital
London
University College London Hospital
London
The Christie Hospital
Manchester
About this study
Official title: ABC-04 a Phase 1B Study of Cisplatin, Gemcitabine and Selumetinib in Patients With Advanced Biliary Tract Cancer
The objective of this study is to establish the recommended dose of selumetinib, a novel MEK inhibitor for use in combination with gemcitabine and cisplatin.
Read the detailed description
This trial aims to evaluate the safety and tolerability of selumetinib in combination with CisGem and to establish the recommended dose to take into phase II studies. Pharmacokinetic and pharmacodynamic endpoints will be assessed and preliminary efficacy data will also be collected.
Patients with Advanced Biliary tract Cancer will receive CisGem regimen and selumetinib. A dose de-escalation scheme will be employed to determine the recommended phase II dose of selumetinib.
Patients will be recruited in cohorts of three and assessed for dose limiting toxicity (DLT) during the first cycle of treatment. Depending on the number of DLTs observed, the cohort may be expanded, the next cohort may be enrolled at a lower dose or the dose may be declared the recommended dose. Patients will receive up to eight cycles of CisGem and may continue to receive selumetinib until progression of disease.
- Being tested
- selumetinib, gemcitabine, cisplatin
- Keywords
- unresectable, advanced
- Medical subject headings
- Biliary Tract Neoplasms, Cholangiocarcinoma, Gallbladder Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
selumetinibDrug
Also called AZD6244
The starting dose of selumetinib will depend on the cohort. The first dose of selumetinib to be studied will be 75 mg twice daily (bd). Selumetinib will be taken every day (continuously) either once or twice a day, depending on the dose. Treatment with selumetinib may continue until disease progression.
gemcitabineDrug
gemcitabine: taken in combination with cisplatin will be given at 1000 mg/m*2 in 250 - 500 ml 0.9% saline over 30 minutes by intravenous infusion on days 1, and 8 of each 21-day cycle for eight cycles in total
cisplatinDrug
cisplatin: 25 mg/m*2 in 1000 ml 0.9% saline given over 1 hour followed by 500mls 0.9% saline over 30 minutes followed by gemcitabine on days 1, and 8 of each 21-day cycle for eight cycles in total
| Study group | Role | What they receive |
|---|---|---|
| single armed | Experimental | This is not a randomised trial, there is only one study group. All patients will receive cisplatin/gemcitabine chemotherapy in addition to oral daily dosing of selumetinib Receives: Drug: selumetinib; Drug: gemcitabine; Drug: cisplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
To investigate the safety and tolerability of the combination of cisplatin, gemcitabine and selumetinib, and to establish the recommended phase II dose of selumetinib when given in this combination.
To investigate the safety and tolerability of the combination of cisplatin, gemcitabine (CisGem) and selumetinib and to establish the recommended phase II dose of selumetinib when given in this combination.
The recommended dose of selumetinib to use in combination with CisGem in future studies will be the dose at which less than 33% of patients experience a DLT. The recommended dose will not be higher than 75mg/m*2
Measured: from baseline to 28 days post last patient last treatment
Secondary outcomes (1)
Response rate
To make a preliminary assessment of efficacy in terms of tumour control.
Measured: From baseline to end of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Nov 2010 (estimated)
- Study startFeb 2012
- Primary completionMar 2013
- Study completionMay 2016
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 NeoplasmsStudies of the same condition, open and under way.
- More trials run by University College, LondonThe sponsor's other registered studies.
- 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
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- University College, London
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca
- Responsible party
- Sponsor
- Investigators
- John Bridgewater, MBBS, Principal investigator, UCL
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01242605
- Sponsor's protocol ID
- UCL/10/0254
- Other IDs
- 2010-018522-39
- Acronym
- ABC-04
- Status last verified
- Oct 2015
- First submitted
- 6 Jul 2010
- Last updated
- 13 May 2016
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Publications
Bridgewater J, Lopes A, Beare S, Duggan M, Lee D, Ricamara M, McEntee D, Sukumaran A, Wasan H, Valle JW. A phase 1b study of Selumetinib in combination with Cisplatin and Gemcitabine in advanced or metastatic biliary tract cancer: the ABC-04 study. BMC Cancer. 2016 Feb 24;16:153. doi: 10.1186/s12885-016-2174-8.
PubMed 26912134
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- ABC-04 a Phase 1B Study of Cisplatin, Gemcitabine and Selumetinib in Patients With Advanced Biliary Tract Cancer
- ClinicalTrials.gov ID
- NCT01242605
- Acronym / sponsor ID
- ABC-04 / UCL/10/0254
- Keywords
- unresectable, advanced
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- University College, LondonUniversity, hospital or other
- Collaborators
- AstraZeneca
- Study start
- Feb 2012
- Primary completion
- Mar 2013 (actual)
- Study completion
- May 2016 (actual)
- First posted
- 17 Nov 2010 (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 objective of this study is to establish the recommended dose of selumetinib, a novel MEK inhibitor for use in combination with gemcitabine and cisplatin.
Detailed description
This trial aims to evaluate the safety and tolerability of selumetinib in combination with CisGem and to establish the recommended dose to take into phase II studies. Pharmacokinetic and pharmacodynamic endpoints will be assessed and preliminary efficacy data will also be collected.
Patients with Advanced Biliary tract Cancer will receive CisGem regimen and selumetinib. A dose de-escalation scheme will be employed to determine the recommended phase II dose of selumetinib.
Patients will be recruited in cohorts of three and assessed for dose limiting toxicity (DLT) during the first cycle of treatment. Depending on the number of DLTs observed, the cohort may be expanded, the next cohort may be enrolled at a lower dose or the dose may be declared the recommended dose. Patients will receive up to eight cycles of CisGem and may continue to receive selumetinib until progression of disease.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| single armed | Experimental | Drug: selumetinib, Drug: gemcitabine, Drug: cisplatinThis is not a randomised trial, there is only one study group. All patients will receive cisplatin/gemcitabine chemotherapy in addition to oral daily dosing of selumetinib |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- A histopathological or cytological diagnosis of non-resectable, recurrent or metastatic biliary tract (intra- or extra-hepatic), gallbladder or ampullary carcinoma
- ECOG performance status 0, 1, or 2
- Age ≥ 18
- Estimated life expectancy > 3 months
- Adequate haematological function:
Key exclusion criteria (15 listed)
- Any prior exposure to MEK, Ras, or Raf inhibitors
- Cardiac conditions as follows:
- Incomplete recovery from previous surgery.
- Patients undergoing current treatment with curative intent.
- History of prior malignancy that could interfere with the response evaluation (exceptions include in-situ carcinoma of the cervix treated by cone-biopsy/resection, non-metastatic basal and/or squamous cell carcinomas of the skin, any early stage (stage I) malignancy adequately resected for cure greater than 5 years previously).
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 |
|---|---|---|
| selumetinibAlso: AZD6244The starting dose of selumetinib will depend on the cohort. The first dose of selumetinib to be studied will be 75 mg twice daily (bd). Selumetinib will be taken every day (continuously) either once or twice a day, depending on the dose. Treatment with selumetinib may continue until disease progression. | Drug | single armed |
| gemcitabinegemcitabine: taken in combination with cisplatin will be given at 1000 mg/m*2 in 250 - 500 ml 0.9% saline over 30 minutes by intravenous infusion on days 1, and 8 of each 21-day cycle for eight cycles in total | Drug | single armed |
| cisplatincisplatin: 25 mg/m*2 in 1000 ml 0.9% saline given over 1 hour followed by 500mls 0.9% saline over 30 minutes followed by gemcitabine on days 1, and 8 of each 21-day cycle for eight cycles in total | Drug | single armed |
Primary outcome
To investigate the safety and tolerability of the combination of cisplatin, gemcitabine and selumetinib, and to establish the recommended phase II dose of selumetinib when given in this combination.
Time frame: from baseline to 28 days post last patient last treatment
To investigate the safety and tolerability of the combination of cisplatin, gemcitabine (CisGem) and selumetinib and to establish the recommended phase II dose of selumetinib when given in this combination. The recommended dose of selumetinib to use in combination with CisGem in future studies will be the dose at which less than 33% of patients experience a DLT. The recommended dose will not be higher than 75mg/m*2
1 secondary outcome
Response rate
Time frame: From baseline to end of treatment
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 13 May 2016.
- Derived from this study: PubMed 26912134Bridgewater J, Lopes A, Beare S, Duggan M, Lee D, Ricamara M, McEntee D, Sukumaran A, Wasan H, Valle JW. A phase 1b study of Selumetinib in combination with Cisplatin and Gemcitabine in advanced or metastatic biliary tract cancer: the ABC-04 study. BMC Cancer. 2016 Feb 24;16:153. doi: 10.1186/s12885-016-2174-8.
- PublicationLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
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Not yet recruitingPhase 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.
John Bridgewater, MBBS principal investigator
UCL
3 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 selumetinib, gemcitabine and cisplatin in people with Biliary Tract Neoplasms and Cholangiocarcinoma, run by University College, London at 3 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 20 inclusion and 15 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 13 May 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 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?
To investigate the safety and tolerability of the combination of cisplatin, gemcitabine and selumetinib, and to establish the recommended phase II dose of selumetinib when given in this combination. (time frame: from baseline to 28 days post last patient last treatment). 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 NCT01242605, 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 13 May 2016.