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Liver and Intrahepatic Biliary Tract CancerPhase 2NCT00553332

Selumetinib in Treating Patients With Biliary Cancer That Cannot Be Removed By Surgery

A Phase 2 study testing selumetinib and laboratory biomarker analysis in people with Liver and Intrahepatic Biliary Tract Cancer and Recurrent Extrahepatic Bile Duct Cancer, run by National Cancer Institute (NCI) at 7 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This phase II trial is studying how well selumetinib works in treating patients with biliary cancer that cannot be removed by surgery. Selumetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
selumetinib and laboratory biomarker analysis
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
29 participants
Where
7 sitesUnited States
Study dates
Nov 2007to Jan 2013
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Histologically confirmed biliary tract carcinoma
  • Surgically unresectable disease
  • Meets any of the following criteria for biliary cancers only:
  • Received ≤ 1 prior systemic anticancer therapy, including chemoembolization
  • Received prior cryotherapy, radiofrequency ablation, ethanol injection, transarterial chemoembolization, or photodynamic therapy AND meets the following criteria:
  • More than 6 weeks have elapsed since any of the prior therapy described above
Show all 40Show fewer
  • Indicator lesion(s) must be outside the area of prior treatment OR must demonstrate clear evidence of disease progression if the only indicator lesion is inside the prior treatment area
  • Indicator lesion must have clearly distinct edges on CT scan
  • Prior radiotherapy with or without the use of a fluoropyrimidine as a radiosensitizer is allowed, provided more than 12 weeks have elapsed since treatment
  • Fresh or paraffin-embedded tissue from tumor blocks must be available for review
  • Measurable disease, defined as ≥ 1 unidimensionally measurable lesion > 20 mm by conventional techniques or > 10 mm by spiral CT scan
  • No known brain metastases
  • Life expectancy > 12 weeks
  • ECOG performance status (PS) 0-1 or Karnofsky PS 70-100%
  • ANC ≥ 1,500/μL
  • Platelet count ≥ 75,000/μL
  • Total bilirubin ≤ 2 times upper limit of normal(ULN)
  • AST or ALT ≤ 3 times ULN
  • Serum albumin ≥ 2.5 mg/dL
  • INR ≤ 1.5 (not receiving anticoagulation therapy)
  • Creatinine normal or creatinine clearance ≥ 60 mL/min
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile women must use effective contraception during and for four weeks after the last dose of AZD6244
  • Fertile men must use effective contraception during and for 16 weeks after the last dose of AZD6244
  • No significant traumatic injury within the past 3 weeks
  • No uncontrolled symptoms consistent with encephalopathy
  • No history of allergic reactions attributed to compounds of similar chemical or biologic composition to AZD6244 or its excipient, Captisol®
  • No QTc interval > 500 msecs or other factors that increase the risk of QT prolongation or arrhythmic events (e.g., hypokalemia or family history of long QT interval syndrome), including NYHA class III-IV heart failure
  • No other malignancy within the past 3 years, except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
  • No refractory nausea and vomiting, chronic gastrointestinal disease (e.g., inflammatory bowel disease), or significant bowel resection that would preclude adequate absorption
  • No uncontrolled concurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situation that would limit compliance with study requirements
  • No malignant hypertension within the past year
  • No prior sorafenib or MEK inhibitors
  • More than 4 weeks since prior chemotherapy, biologic therapy, or immunotherapy (6 weeks for nitrosoureas or mitomycin C) and recovered to ≤ grade 1 adverse events
  • No major surgery within the past 3 weeks
  • No other concurrent investigational agents
  • No concurrent requirement for medication that can prolong the QT interval
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No concurrent consumption of grapefruit or grapefruit juice

Who cannot join

None listed.

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

United States7 sites

  • University of Michigan Cancer Center (UMCC) Research Base

    Ann Arbor, Michigan, 48109-0352

  • Emory University

    Atlanta, Georgia, 30322

  • University of North Carolina

    Chapel Hill, North Carolina, 27599

  • Ohio State University Medical Center

    Columbus, Ohio, 43210

  • Wayne State University

    Detroit, Michigan, 48202

  • Vanderbilt University

    Nashville, Tennessee, 37232

  • H. Lee Moffitt Cancer Center and Research Institute

    Tampa, Florida, 33612

Other trials in United States

About this study

Official title: A Phase 2 Study of AZD6244 in Biliary Cancers

This phase II trial is studying how well selumetinib works in treating patients with biliary cancer that cannot be removed by surgery. Selumetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To evaluate the objective response rate (complete response [CR] and partial response [PR]) in patients with unresectable biliary carcinoma treated with AZD6244 (selumetinib).

SECONDARY OBJECTIVES:

  1. To evaluate the toxicity profile of this drug in these patients. II. To evaluate the 6- and 12-month survival, 6-month progression-free survival, and overall survival rates of patients treated with this drug.

III. To correlate genetic mutations, epigenetic silencing, and/or protein levels of RAS/RAF/MEK/ERK signaling pathway activation with therapeutic efficacy of AZD6244 in these patients.

IV. To genotype tumors for the presence of RAS mutations (i.e., NRAS, KRAS, HRAS) and BRAF mutations (e.g., V600E) in biliary tumor samples from these patients.

  1. To assess the presence of activation of the MEK1, MEK2, ERK, and/or Akt pathways in tumor samples from these patients.

VI. To assess the epigenetic alterations (i.e., methylation) affecting the level of gene/protein expression of RASSF1A, NORE1A, and NORE1B in tumor samples from these patients.

OUTLINE:

Patients receive oral selumetinib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Formalin fixed paraffin-embedded tissue blocks or fresh tissue samples are obtained from all patients prior to treatment. Tissue samples are analyzed by immunohistochemistry for the expression level of target proteins (MEK, p-MEK, ERK, p-ERK, Akt, p-AKT, RASSF1A, NORE1A and NORE1B); PCR for mutational status of target genes RAS, BRAF and EGFR); and in methylation-specific PCR for methylation of target gene promoters (promoters for RASSF1A, NORE1A and NORE1B). Samples are also analyzed by quantitative real-time PCR to compare methylation status. Fresh frozen tissue, when available, is evaluated by Western analysis to measure expression levels of target proteins.

After completion of study treatment, patients are followed up for 4 weeks.

Being tested
selumetinib, laboratory biomarker analysis
Medical subject headings
Carcinoma, Hepatocellular, Bile Duct Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • selumetinibDrug

    Also called ARRY-142886, AZD6244

    Given orally

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT00553332
Study groupRoleWhat they receive
Treatment (enzyme inhibitor therapy)ExperimentalPatients receive oral selumetinib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: selumetinib; Other: laboratory biomarker analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective Response Rate (CR and PR)

    Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

    Measured: Every 8 weeks

Secondary outcomes (5)

  1. Toxicity Profile of AZD6244

    Toxicitity will be assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v 3.0

    Measured: From the time of first treatment with AZD6244, assessed up to 4 weeks

  2. Median Progression Free Survival for Patients

    Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

    Measured: Up to 6 months

  3. Overall Survival

    Measured: Up to 12 months

  4. RAS/RAF/MEK/ERK Signaling Pathway Activation

    Measured: At baseline

  5. Protein Levels of RAS/RAF/MEK/ERK Signaling Pathway Activation

    Measure the proteins levels of RAS/RAF/MEK/ERK signaling pathway activation to AZD6244

    Measured: At baseline

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Nov 2007 (estimated)
  2. Study startNov 2007
  3. Primary completionJan 2013
  4. Study completionJan 2013

Resources

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
29 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00553332
Sponsor's protocol ID
NCI-2009-00251
Other IDs
OSU 07056, OSU-07056, CDR0000573452, N01CM62208, N01CM62207
Status last verified
Mar 2016
First submitted
2 Nov 2007
Last updated
22 Apr 2016

Publications

  • Bekaii-Saab T, Phelps MA, Li X, Saji M, Goff L, Kauh JS, O'Neil BH, Balsom S, Balint C, Liersemann R, Vasko VV, Bloomston M, Marsh W, Doyle LA, Ellison G, Grever M, Ringel MD, Villalona-Calero MA. Multi-institutional phase II study of selumetinib in patients with metastatic biliary cancers. J Clin Oncol. 2011 Jun 10;29(17):2357-63. doi: 10.1200/JCO.2010.33.9473. Epub 2011 Apr 25.

    PubMed 21519026

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing selumetinib and laboratory biomarker analysis in people with Liver and Intrahepatic Biliary Tract Cancer and Recurrent Extrahepatic Bile Duct Cancer, run by National Cancer Institute (NCI) at 7 sites in United States.

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 40 inclusion and 0 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 22 Apr 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in United States. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 Apr 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Objective Response Rate (CR and PR) (time frame: Every 8 weeks). 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 NCT00553332, 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 22 Apr 2016.

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