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Thyroid CancerNCT00970359

Reacquisition of Radioactive Iodine (RAI) Uptake of RAI-Refractory Metastatic Thyroid Cancers by Pretreatment With the Selective MEK Inhibitor AZD6244

A study testing AZD6244 in people with Thyroid Cancer, run by Memorial Sloan Kettering Cancer Center at 1 site 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

The purpose of this study is to find out if the drug AZD6244 can improve the radioactive iodine uptake by the patient's metastatic thyroid cancer. The investigator will also be testing the tumor specimen taken at the time of your surgery for specific genetic changes to see if one of them in particular (the BRAF… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Thyroid Cancer
What is being tested?
AZD6244
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
1 siteUnited States
Study dates
Sep 2009to Apr 2013
Phase
Interventional
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

  • Patients > or = to 18 years-old
  • Patients must have histopathologically confirmed at MSKCC differentiated thyroid carcinoma of follicular cell origin (D-TC-FCO), which includes papillary, follicular, or Hürthle cell histology, along with their respective variants.
  • Pathology specimen from the original tumor (thyroid) and/or metastases must be available for genotyping.
  • RAI-refractory metastatic disease on structural imaging, defined as any one of the following (as described in MSKCC protocol 08-066):
  • index metastatic lesion non-RAI avid on a diagnostic RAI scan performed up to 2 years prior to enrolment in the current study, OR
  • RAI-avid metastatic lesion which remained stable in size or progressed despite RAI treatment 6 months or more prior to entry in the study. Lesions will be assessed by 2 independent observers in nuclear medicine and in endocrinology. There is no minimal size limit for the index lesion.
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  • Patients with FDG avid lesions
  • Evaluable disease by RECIST
  • Preliminary reproductive toxicology data indicate that AZD6244 can have adverse effects on embryofetal development and survival at dose levels that do not induce maternal toxicity in mice. For this reason, female patients will need to be post-menopausal or with negative serum pregnancy test if pre-menopausal. Patients of childbearing potential must agree to employ adequate contraception throughout the study.
  • ANC > 1500 per mm3, platelets > 100,000 per mm3, and hemoglobin > 9 g/dL
  • ALT/SGOT and AST/SGPT ≤ 2.5 X upper limit of normal (ULN)
  • Bilirubin ≤ 1.5 X ULN
  • Ability to understand and the willingness to sign a written informed consent document.

Who cannot join

  • Patients may not be receiving any other investigational agents.
  • Patient with chronic renal insufficiency, as defined initially by an estimated creatinine clearance of < 30 ml/minute calculated using the Cockcroft and Gault equation: (140 - age in years) X (weight in kg) X (0.85 if female)/72 X serum Cr. If estimated creatinine clearance is < 30 ml/min, a 24 hour urine creatinine clearance may be collected and a patient would be eligible if the creatinine clearance is >30 ml/min.
  • Patients unable to follow a low iodine diet, patients requiring medication with high content in iodide (amiodarone), or patients receiving IV iodine containing contrast as part of radiographic procedure.
  • Patients with clinically significant cardiovascular disease as defined by the following:
  • LVEF < institutional LLN
  • New York Heart Association grade III or greater congestive heart failure
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  • uncontrolled hypertension, defined as systolic blood pressure > 180 mmHg OR diastolic blood pressure > 105 mmHg, on at least 2 repeated determinations on separate days within past 3 months
  • Uncontrolled coronary artery disease, angina, congestive heart failure, or ventricular arrhythmia requiring acute medical management.
  • Patient with known hypersensitivity to Thyrogen (human recombinant thyrotropin).
  • Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to agents used in the study.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements.
  • Pregnant women will be ineligible; breast feeding should be discontinued if the mother is treated with AZD6244.
  • Brain metastases or spinal cord compression unless treated and stable (for at least 3 months) off steroids.
  • Mean QTc interval >450 ms

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Memorial Sloan-Kettering Cancer Center

    New York, New York, 10065

Other trials in United States

About this study

Official title: Reacquisition of RAI Uptake of RAI-Refractory Metastatic Thyroid Cancers by Pretreatment With the Selective MEK Inhibitor AZD6244: A Pilot Study

The purpose of this study is to find out if the drug AZD6244 can improve the radioactive iodine uptake by the patient's metastatic thyroid cancer. The investigator will also be testing the tumor specimen taken at the time of your surgery for specific genetic changes to see if one of them in particular (the BRAF oncogene) makes your cancer more likely to become sensitive to radioactive iodine after treatment with the drug.

The investigators want to find out if AZD6244 helps to increase the entry of radioactive iodine into thyroid cancer cells that have spread and are resistant to radioactive iodine therapy, especially if they have the BRAF mutation. To measure how much iodine can enter your cancer, the investigators will use iodine-124, a different form of radioactive iodine. Iodine-124 allows the investigators to measure precisely how much radioactivity can enter the cancer cells, whereas iodine-131 does not. The process of scanning with iodine-124 is called "lesional dosimetry". Iodine-124 is an investigational agent approved by the FDA (Food and Drug Administration) for use in this research study.

Conditions
Thyroid Cancer
Being tested
AZD6244
Keywords
thyroid, metastases, AZD6244, 09-048
Medical subject headings
Thyroid Neoplasms, Thyroid Diseases, Neoplasm Metastasis

What participants receive

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

  • AZD6244Biological

    Within 1 week of starting the study: Low iodine diet

    The patient will receive three bottles of capsules containing the drug AZD6244. Each capsule contains 25 milligrams of AZD6244. They will take 3 capsules orally, by mouth twice a day for 4 weeks. AZD6244 should be taken on an empty stomach (either one hour before or 2 hours after meals). AZD6244 capsules should be taken with water only. Lesional dosimetry with iodine-124 PET will be done twice, at the beginning and at the end of the study. This is done the same way that a radioactive iodine scan is done and is spread out over 5 days. It requires injection with human recombinant TSH (Thyrogen) on day 1 and 2, as well as blood tests on day 1 and day 5. On day 3, you will receive the iodine-124 in form of an oral drink, and the PET scan will be obtained on day 5. You will need to follow a low iodine diet starting 5 days before and throughout the process.

Study groups in NCT00970359
Study groupRoleWhat they receive
pts with thyroid cancer with and without BRAF mutationExperimentalPatients receive selumetinib orally (PO) twice daily (BID) for 4 weeks. Within 1 month, patients with adequate RAI uptake may receive 131I per standard of care and continue selumetinib until 2 days following 131I.
Receives: Biological: AZD6244

What is being measured

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

  1. Number of Patients Whose Tumor(s) Acquire an Increased Propensity for Iodine Uptake as Detected on Iodine-124 Positron Emission Tomography Scan

    Measured: 2 years

  2. Tumor Response Defined as Either a Complete Response or Partial Response

    as defined by the RECIST v1.1 criteria Descriptive statistics will be used to summarize the data.

    Measured: 6 months

Secondary outcomes (1)

  1. Change From Baseline in Serum Thyroglobulin Levels After Treatment With 131I

    Will perform a Wilcoxon signed rank test for paired samples to compare the serum thyroglobulin level before and after 131I treatment in the subset of patients treated with 131I following AZD6244.

    Measured: At 2 months and 6 months after Radioiodine administration

Timeline

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

  1. First posted2 Sep 2009 (estimated)
  2. Study startSep 2009
  3. Primary completionApr 2013
  4. Study completionApr 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 N/A
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00970359
Sponsor's protocol ID
09-048
Status last verified
Mar 2017
First submitted
1 Sep 2009
Last updated
12 Apr 2017
Data monitoring committee
Yes

Publications

  • Ho AL, Grewal RK, Leboeuf R, Sherman EJ, Pfister DG, Deandreis D, Pentlow KS, Zanzonico PB, Haque S, Gavane S, Ghossein RA, Ricarte-Filho JC, Dominguez JM, Shen R, Tuttle RM, Larson SM, Fagin JA. Selumetinib-enhanced radioiodine uptake in advanced thyroid cancer. N Engl J Med. 2013 Feb 14;368(7):623-32. doi: 10.1056/NEJMoa1209288.

    PubMed 23406027

Questions about this trial

What is this clinical trial studying?

A study testing AZD6244 in people with Thyroid Cancer, run by Memorial Sloan Kettering Cancer Center at 1 site 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 13 inclusion and 14 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 12 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Apr 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?

Number of Patients Whose Tumor(s) Acquire an Increased Propensity for Iodine Uptake as Detected on Iodine-124 Positron Emission Tomography Scan (time frame: 2 years). The study lists 2 primary outcomes in all. 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 NCT00970359, 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 12 Apr 2017.

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