NCT01242605

Brief 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
13

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Feb 2012

Longer than P75 for phase_1

Geographic Reach
1 country

3 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 6, 2010

Completed
4 months until next milestone

First Posted

Study publicly available on registry

November 17, 2010

Completed
1.2 years until next milestone

Study Start

First participant enrolled

February 1, 2012

Completed
1.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2013

Completed
3.2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2016

Completed
Last Updated

May 13, 2016

Status Verified

October 1, 2015

Enrollment Period

1.1 years

First QC Date

July 6, 2010

Last Update Submit

May 11, 2016

Conditions

Biliary Tract NeoplasmsCholangiocarcinomaGallbladder Neoplasms

Keywords

unresectableadvanced

Outcome Measures

Primary Outcomes (1)

  • 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

    from baseline to 28 days post last patient last treatment

Secondary Outcomes (1)

  • Response rate

    From baseline to end of treatment

Study Arms (1)

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

Drug: selumetinibDrug: gemcitabineDrug: cisplatin

Interventions

selumetinibDRUG

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.

Also known as: AZD6244
single armed
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

single armed
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

single armed

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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)
  • 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
  • +4 more criteria

You may not qualify if:

  • 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%
  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Hammersmith Hospital

London, United Kingdom

Location

University College London Hospital

London, United Kingdom

Location

The Christie Hospital

Manchester, United Kingdom

Location

Related Publications (1)

  • 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.

    PMID: 26912134DERIVED

Related Links

MeSH Terms

Conditions

Biliary Tract NeoplasmsCholangiocarcinomaGallbladder Neoplasms

Interventions

AZD 6244GemcitabineCisplatin

Condition Hierarchy (Ancestors)

Digestive System NeoplasmsNeoplasms by SiteNeoplasmsBiliary Tract DiseasesDigestive System DiseasesAdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeGallbladder Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic CompoundsDeoxycytidineCytidinePyrimidine NucleosidesPyrimidinesHeterocyclic Compounds, 1-RingChlorine CompoundsInorganic ChemicalsNitrogen CompoundsPlatinum Compounds

Study Officials

  • John Bridgewater, MBBS

    UCL

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 6, 2010

First Posted

November 17, 2010

Study Start

February 1, 2012

Primary Completion

March 1, 2013

Study Completion

May 1, 2016

Last Updated

May 13, 2016

Record last verified: 2015-10

Locations

GB(3)