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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
University College, London
ClinicalTrials.gov Identifier:
NCT01242605
First received: July 6, 2010
Last updated: September 26, 2013
Last verified: September 2013
  Purpose

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.


Condition Intervention Phase
Biliary Tract Neoplasms
Cholangiocarcinoma
Gallbladder Neoplasms
Drug: selumetinib
Drug: gemcitabine
Drug: cisplatin
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: ABC-04 a Phase 1B Study of Cisplatin, Gemcitabine and Selumetinib in Patients With Advanced Biliary Tract Cancer

Resource links provided by NLM:


Further study details as provided by University College, London:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

    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



Secondary Outcome Measures:
  • Response rate [ Time Frame: From baseline to end of treatment ] [ Designated as safety issue: No ]
    To make a preliminary assessment of efficacy in terms of tumour control.


Estimated Enrollment: 30
Study Start Date: February 2012
Estimated Study Completion Date: January 2015
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 * 10g/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 >/= 100,000/mm*3)
  • 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 60, isotope EDTA confirmation of adequate renal function is required
  • No evidence of active uncontrolled infection (patients on antibiotics are eligible)
  • Capable of giving written informed consent

Exclusion Criteria:

  • 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 (eg 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, in those randomised to cisplatin, should be followed by repeat audiograms prior to cycle 2.
  • Patients with any grade NYHA cardiomyopathy and uncontrolled hypertension (>150/95mmhg).
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01242605

Locations
United Kingdom
University College London Hospital
London, United Kingdom
Sponsors and Collaborators
University College, London
AstraZeneca
Investigators
Principal Investigator: John Bridgewater, MD UCL
  More Information

No publications provided

Responsible Party: University College, London
ClinicalTrials.gov Identifier: NCT01242605     History of Changes
Other Study ID Numbers: ABC-04, 2010-018522-39
Study First Received: July 6, 2010
Last Updated: September 26, 2013
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by University College, London:
unresectable
advanced

Additional relevant MeSH terms:
Biliary Tract Neoplasms
Neoplasms
Gallbladder Neoplasms
Cholangiocarcinoma
Digestive System Neoplasms
Neoplasms by Site
Biliary Tract Diseases
Digestive System Diseases
Gallbladder Diseases
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Gemcitabine
Cisplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on April 16, 2014