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Recurrent Thyroid Gland CarcinomaPhase 2NCT00559949

Selumetinib in Treating Patients With Papillary Thyroid Cancer That Did Not Respond to Radioactive Iodine

A Phase 2 study testing Laboratory Biomarker Analysis and Selumetinib in people with Recurrent Thyroid Gland Carcinoma and Stage I Thyroid Gland Papillary Carcinoma, run by National Cancer Institute (NCI) at 6 sites in 2 countries.

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 papillary thyroid cancer that did not respond to radioactive iodine. 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?
Laboratory Biomarker Analysis and Selumetinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
39 participants
Where
6 sitesin 2 countries
Study dates
Dec 2007to Aug 2016
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 or cytologically confirmed papillary thyroid cancer or papillary thyroid cancer with follicular elements
  • No longer amenable to radioactive iodine therapy or curative surgical resection
  • Tumor is no longer iodine avid
  • Tumor did not respond to the most recent radioactive iodine treatment
  • Patient is ineligible for further radioactive iodine therapy due to medical contraindications (e.g., lung toxicity)
  • Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 20 mm with conventional techniques or as ≥ 10 mm with spiral CT scan
Show all 34Show fewer
  • Evidence of disease progression (objective growth of existing tumors)
  • New or enlarging measurable lesions within the past 12 months
  • If the most recent imaging study is older than 12 months, patients will still be eligible if objectively measurable disease progression is associated with clinical symptoms
  • Archival tumor tissue available for mutational analysis
  • No known brain metastases
  • ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
  • Life expectancy > 12 weeks
  • WBC ≥ 3,000/µL
  • ANC ≥ 1,500/µL
  • Platelet count ≥ 100,000/µL
  • Total bilirubin normal
  • AST and ALT < 2.5 times upper limit of normal
  • Creatinine normal OR creatinine clearance ≥ 60 mL/min
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception prior to, during, and for 4 weeks after completion of study treatment
  • Able to understand and willing to sign a written informed consent document
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to selumetinib (AZD6244) or its excipient Captisol®
  • QTc interval > 450 msec or other factors that increase the risk of QT prolongation
  • Arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome), including heart failure that meets NYHA class III and IV definition
  • Refractory nausea and vomiting, chronic gastrointestinal diseases (e.g., inflammatory bowel disease), or significant bowel resection that would preclude adequate absorption
  • Concurrent uncontrolled illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements
  • At least 4 weeks since prior radiotherapy or chemotherapy (6 weeks for nitrosoureas or mitomycin C)
  • Prior treatment with tyrosine kinase inhibitors that target RET or RAF
  • Prior treatment with MEK inhibitors
  • Concurrent combination antiretroviral therapy for HIV-positive patients
  • Concurrent medication that can prolong the QT interval
  • Other concurrent investigational agents

Who cannot join

None listed.

Trial locations and contacts

6 sites in 2 countries.

6 sites in 2 countries

United States5 sites

  • UNC Lineberger Comprehensive Cancer Center

    Chapel Hill, North Carolina, 27599

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637

  • Vanderbilt University/Ingram Cancer Center

    Nashville, Tennessee, 37232

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111

  • Moffitt Cancer Center

    Tampa, Florida, 33612

Other trials in United States

Canada1 site

  • University Health Network-Princess Margaret Hospital

    Toronto, Ontario, M5G 2M9

Other trials in Canada

About this study

Official title: Phase 2 Study of Selumetinib Hydrogen Sulfate in Iodine-131 Refractory Papillary Thyroid Carcinoma and Papillary Thyroid Carcinoma With Follicular Elements

This phase II trial is studying how well selumetinib works in treating patients with papillary thyroid cancer that did not respond to radioactive iodine. 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. Ascertain the objective response rate (complete response and partial response) in patients with iodine I 131-refractory papillary thyroid cancer treated with selumetinib.

SECONDARY OBJECTIVES:

  1. Determine the toxicity of this treatment in these patients. II. Determine the pharmacokinetic profile of this treatment in these patients. III. Determine the progression-free and overall survival of these patients. IV. Assess proxy measures of treatment response (thyroglobulin and PET scan) in patients treated with selumetinib.

IV. Compare relevant laboratory correlates between responders and non-responders.

OUTLINE: This is a multicenter study.

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

Archived tissue is examined for gene mutations, including RET, BRAF, NTRK, and RAS, by fluorescence in situ hybridization and/or polymerase chain reaction and fluorescence melting curve analysis. Protein expression of ERK and phosphorylated ERK is assessed by immunohistochemical staining.

Blood samples are collected periodically for pharmacokinetic analysis and biomarker assessment (thyroglobulin and antithyroglobulin autoantibodies).

After completion of study therapy, patients are followed periodically for up to 2 years.

Being tested
Laboratory Biomarker Analysis, Selumetinib
Medical subject headings
Thyroid Neoplasms, Thyroid Cancer, Papillary

What participants receive

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

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • SelumetinibDrug

    Also called ARRY-142886, AZD6244, MEK Inhibitor AZD6244

    Selumetinib was administered orally as a free base suspension at a dose of 100 mg twice daily for 28-day cycles. Those participants experiencing Common Terminology Criteria for Adverse Events (CTCAE) v3.0 grade 3 toxicity or worse had their dose reduced to 50 mg twice daily and then to 50 mg once daily, if necessary.

Study groups in NCT00559949
Study groupRoleWhat they receive
Arm IExperimentalPatients receive oral selumetinib twice daily on days 1-28. Treatment repeats every 28 days in the absence of unacceptable toxicity or disease progression.
Receives: Other: Laboratory Biomarker Analysis; Drug: Selumetinib

What is being measured

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

  1. Objective Response Rate (ORR)

    ORR: Complete Response (CR) and Partial Response (PR) evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST). CR: Disappearance of all target lesions. PR: At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. A conservative estimate of the response rate of the best-studied agent in this disease, doxorubicin, is approximately 5%. Therefore, investigators will assume that selumetinib (AZD6244, NSC 741078) would be worth further pursuit if the response rate (CR+PR) were at least 20%.

    Measured: Up to 2 years

Secondary outcomes (3)

  1. Median Progression-Free Survival (PFS)

    PFS is defined as the duration of time from start of treatment to time of progression or death. Progression evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST). Progressive Disease (PD): 20% increase in the sum of appropriate diameters of target measurable lesions over smallest sum observed (over baseline if no decrease during therapy) using the same techniques as baseline, as well as an absolute increase of at least 0.5 cm. Secondary end points include toxicity, progression free survival, and overall survival. Due to the small sample size and absence of high quality historic data for this disease, these analyses were planned to be mostly exploratory and descriptive in nature.

    Measured: Up to 2 years

  2. Occurrence of Treatment Related Adverse Events

    Number of participants with related adverse events, per category and Grade category. Toxicity assessed using NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

    Measured: Up to 2 years

  3. Overall Survival (OS)

    Overall Survival using the Kaplan-Meier method with associated confidence intervals. OS analysis was intended to be mostly exploratory and descriptive in nature.

    Measured: Up to 2 years

Timeline

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

  1. First posted19 Nov 2007 (estimated)
  2. Study startDec 2007
  3. Primary completionAug 2016
  4. Study completionAug 2016

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
39 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00559949
Sponsor's protocol ID
NCI-2009-01056
Other IDs
NCI-2009-01056, LOI 7918, CDR0000574262, LOI 7918, 7918, N01CM62201, N01CM62203, N01CM62208
Status last verified
Dec 2016
First submitted
16 Nov 2007
Last updated
30 Jan 2017
Data monitoring committee
Yes

Publications

  • Hayes DN, Lucas AS, Tanvetyanon T, Krzyzanowska MK, Chung CH, Murphy BA, Gilbert J, Mehra R, Moore DT, Sheikh A, Hoskins J, Hayward MC, Zhao N, O'Connor W, Weck KE, Cohen RB, Cohen EE. Phase II efficacy and pharmacogenomic study of Selumetinib (AZD6244; ARRY-142886) in iodine-131 refractory papillary thyroid carcinoma with or without follicular elements. Clin Cancer Res. 2012 Apr 1;18(7):2056-65. doi: 10.1158/1078-0432.CCR-11-0563. Epub 2012 Jan 12.

    PubMed 22241789

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Laboratory Biomarker Analysis and Selumetinib in people with Recurrent Thyroid Gland Carcinoma and Stage I Thyroid Gland Papillary Carcinoma, run by National Cancer Institute (NCI) at 6 sites in 2 countries.

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 34 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 30 Jan 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States, Canada. 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 30 Jan 2017). 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 (ORR) (time frame: Up to 2 years). 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 NCT00559949, 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 30 Jan 2017.

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