Status:

COMPLETED

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

Lead Sponsor:

University College, London

Collaborating Sponsors:

AstraZeneca

Conditions:

Biliary Tract Neoplasms

Cholangiocarcinoma

Eligibility:

All Genders

18+ years

Phase:

PHASE1

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.

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 pharmacodynam...

Eligibility Criteria

Inclusion

  • 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

  • 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.

Key Trial Info

Start Date :

February 1 2012

Trial Type :

INTERVENTIONAL

Allocation :

ACTUAL

End Date :

May 1 2016

Estimated Enrollment :

13 Patients enrolled

Trial Details

Trial ID

NCT01242605

Start Date

February 1 2012

End Date

May 1 2016

Last Update

May 13 2016

Active Locations (3)

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Page 1 of 1 (3 locations)

1

Hammersmith Hospital

London, United Kingdom

2

University College London Hospital

London, United Kingdom

3

The Christie Hospital

Manchester, United Kingdom