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ABC-04 a Study of Cisplatin, Gemcitabine and Selumetinib in Patients With Advanced Biliary Tract Cancer (ABC-04)

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ClinicalTrials.gov Identifier: NCT01242605
Recruitment Status : Completed
First Posted : November 17, 2010
Last Update Posted : May 13, 2016
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
University College, London

July 6, 2010
November 17, 2010
May 13, 2016
February 2012
March 2013   (Final data collection date for 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 ]
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
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, gecmtiabine and selumetinib and to establsih 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
Complete list of historical versions of study NCT01242605 on ClinicalTrials.gov Archive Site
Response rate [ Time Frame: From baseline to end of treatment ]
To make a preliminary assessment of efficacy in terms of tumour control.
Same as current
Not Provided
Not Provided
 
ABC-04 a Study of Cisplatin, Gemcitabine and Selumetinib in Patients With Advanced Biliary Tract Cancer
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.

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.

Interventional
Phase 1
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • Biliary Tract Neoplasms
  • Cholangiocarcinoma
  • Gallbladder Neoplasms
  • Drug: selumetinib
    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.
    Other Name: AZD6244
  • Drug: gemcitabine
    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
  • Drug: cisplatin
    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
Experimental: single armed
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
Interventions:
  • Drug: selumetinib
  • Drug: gemcitabine
  • Drug: cisplatin
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. Erratum in: BMC Cancer. 2016;16(1):369.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
13
18
May 2016
March 2013   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • 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
  • 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.

Exclusion Criteria:

  • 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.
Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
No
Contact information is only displayed when the study is recruiting subjects
United Kingdom
 
 
NCT01242605
UCL/10/0254
2010-018522-39 ( EudraCT Number )
Yes
Not Provided
Plan to Share IPD: Undecided
University College, London
University College, London
AstraZeneca
Principal Investigator: John Bridgewater, MBBS UCL
University College, London
October 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP