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Metastatic Thyroid CancerPhase 2ERRITINCT04619316

Enhancing Radioiodine Incorporation Into Radio Iodine Refractory Thyroid Cancers With MAPK Inhibition

A Phase 2 study testing Trametinib 2 MG [Mekinist] and Trametinib 2 MG [Mekinist] and Dabrafenib 75 MG (2-0-2) [Tafinlar] in people with Metastatic Thyroid Cancer, run by University Hospital, Essen at 1 site in Germany.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

This is a prospective interventional trial that aims to restore iodine incorporation in tumoral lesions of patients with unresectable, radioiodine-refractory thyroid cancer. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Thyroid Cancer
What is being tested?
Trametinib 2 MG [Mekinist] and Trametinib 2 MG [Mekinist] and Dabrafenib 75 MG (2-0-2) [Tafinlar]
Could I receive a placebo?
No, everyone receives an active treatment
How many people
70 participants
Where
1 siteGermany
Study dates
5 Feb 2018to 31 Dec 2024
Phase
Phase 2
Are there results?
None posted in the registry

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 must have histologically or cytologically confirmed radioiodine refractory metastatic thyroid carcinoma of follicular origin (including papillary and its respective variants).
  • Confirmation of the mutation status of BRAF gene (primary tumor, recurrent tumor, or metastasis) .
  • Patients who do not undergo a systemic treatment with sorafenib or lenvatinib or chemotherapy or with other TKIs or other investigational drugs.
  • Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥ 15 mm with CT scan, MRI, or calipers by clinical exam. Tumors in previously irradiated fields may be considered measureable if there is evidence of tumor progression after radiation treatment.
  • RAI-refractory disease on structural imaging, defined as following:
  • A metastatic lesion that is not radioiodine-avid on a diagnostic or therapeutic radioiodine scan performed less than 1 year prior to enrollment in the current study, There are no size limitations for the index lesion used to satisfy this entry criterion.
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  • No recent treatment for thyroid cancer as defined as:
  • No prior 131I therapy is allowed < 6 months prior to initiation of therapy on this protocol. A diagnostic study using < 400 MBq (±100) of 131I is not considered 131I therapy.
  • No external beam radiation therapy < 4 weeks prior to initiation of therapy on this protocol. (Previous treatment with radiation for any indication is allowed if the investigator judges that the previous radiation does not significantly compromise patient safety on this protocol.)
  • No chemotherapy or targeted therapy (e.g., tyrosine kinase inhibitor) is allowed < 4 weeks prior to the initiation of therapy on this protocol.
  • Age ≥ 18 years
  • ECOG performance status ≤ 2.
  • Life expectancy of greater than 3 months. Able to swallow and retain orally-administered medication and does not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels.
  • Patients must have normal organ and bone marrow function as defined below:
  • Absolute neutrophil count (ANC) > 1.5x10^9/L
  • Hemoglobin ≥ 9 g/dL
  • Platelets ≥ 100 x 10^9/L
  • Albumin ≥ 2.5 g/dL
  • Total bilirubin ≤ 1.5x institutional ULN
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2x institutional ULN unless it is related to the primary disease
  • creatinine ≤ 1.5 mg/dL OR calculated creatinine clearance (Cockcroft-Gault formula) ≥ 50 mL/min OR 24-hour urine creatinine clearance ≥ 50 mL/min
  • Negative pregnancy test within 7 days prior to starting the study premenopausal women. Women of non-childbearing potential may be included without pregnancy test if they are either surgically sterile or have been postmenopausal for ≥ 1 year.
  • Fertile men and women must use an effective method of contraception during treatment and for at least 6 months after completion of treatment as directed by their physician. Effective methods of contraception are defined as those, which result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly (for example implants, injectables, combined oral contraception or intra-uterine devices). At the discretion of the investigator, acceptable methods of contraception may include total abstinence in cases where the lifestyle of the patient ensures compliance. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, postovulation methods] and withdrawal are not acceptable methods of contraception.)
  • Ability to understand and the willingness to sign a written informed consent document.
  • Patients must agree to undergo to research biopsy of a malignant lesion if the mutation status cannot be proven through archival tissue specimen.
  • Availability of archival tumor tissue from the thyroid cancer primary or metastasis (a tissue block or a minimum of 30 unstained slides would be required. Patients with less archival tissue available may still be eligible for the study after discussion with the Principal Investigator). This does not apply to patients who undergo a biopsy.

Who cannot join

  • Concomitant malignancies or previous malignancies of life-limiting potential within the last 3 years.
  • Use of other investigational drugs within 28 days preceding the first dose of drug treatment during this study.
  • Known leptomeningeal or brain metastases or spinal metastases.
  • Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to trametinib and/or to dabrafenib or other known contents of the two investigational drugs.
  • History or evidence of cardiovascular risk including any of the following:
  • History or evidence of current, clinically significant uncontrolled arrhythmias (exception: patients with controlled atrial fibrillation for > 30 days prior to the initiation of therapy on this protocol are eligible).
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  • History of acute coronary syndromes (specifically, myocardial infarction and unstable angina), severe/unstable angina, coronary angioplasty, or stenting within 6 months prior to the initiation of therapy on this protocol.
  • History of symptomatic congestive heart failure within 6 months prior to the initiation of therapy on this protocol.
  • History of cerebrovascular attack or transient ischemic attack within 6 months prior to the initiation of therapy on this protocol.
  • 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, lactating, or breast feeding women.
  • Patients unable to follow a low iodine diet or requiring medication with high content in iodide (amiodarone).
  • Patients who received iodinated intravenous contrast as part of a radiographic procedure within 3 months of study registration. Those that have had iodinated intravenous contrast within this time frame may still be eligible if a urinary iodine analysis reveals that the excess iodine has been adequately cleared after the last intravenous contrast administration.
  • Unwillingness or inability to comply with study and follow-up procedures.
  • Disorders of eye background as listed in the respective study drug prescribing information.
  • Patients with pancreatitis, prolonged QTc-time on EKG, uncontrolled hypertension, thrombosis or high risk of bleedings.
  • Condition of patient which is critical to participate in this study in the discretion of the PI.

Trial locations and contacts

1 site in 1 country.

Wolfgang P Fendler, MD contact

+49 201 723 2032

wolfgang.fendler@uk-essen.de

Manuel M Weber, MD contact

+49 201 723 2032

manuel.weber@uk-essen.de

Germany1 site, 1 recruiting

  • Manuel M. Weber

    Essen, North Rhine-Westphalia, 45147

    Wolfgang P Fendler, MD, +49 201 723 2032, wolfgang.fendler@uk-essen.de

    Manuel M Weber, MD, +49 201 723 2032, manuel.weber@uk-essen.de

    Recruiting

Other trials in Germany

About this study

Official title: Enhancing Radioiodine Incorporation Into Radio Iodine Refractory Thyroid Cancers With MAPK Inhibition: A Single Center Pilot Study

This is a prospective interventional trial that aims to restore iodine incorporation in tumoral lesions of patients with unresectable, radioiodine-refractory thyroid cancer.

Read the detailed description

This is a prospective interventional study testing the hypothesis that the inhibition of MEK can restore iodine incorporation in BRAF wild type (WT) and a combined inhibition of BRAF and MEK can restore iodine incorporation in BRAFV600E mutant (MUT), radioiodine-refractory (RAIR) thyroid cancer. Patients with proven iodine negative tumor lesion(s) will be included in this study. Patients will then receive Trametinib (WT-group) or Dabrafenib and Trametinib combination-therapy (MUT-group) for approximately 3 weeks, after which a Thyrogen-stimulated 123I SPECT imaging will be performed. For patients whose tumor(s) demonstrate sufficient iodine incorporation in the post drug treatment 123I SPECT imaging, a treatment according to guidelines for iodine positive lesions will be performed. The follow up of the patients will be conducted as standard of care.

Being tested
Trametinib 2 MG [Mekinist], Trametinib 2 MG [Mekinist] and Dabrafenib 75 MG (2-0-2) [Tafinlar]
Medical subject headings
Thyroid Neoplasms

What participants receive

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

  • Trametinib 2 MG [Mekinist]Drug

    Monotherapy with Trametinib is given in patients with BRAF wildtype.

  • Trametinib 2 MG [Mekinist] and Dabrafenib 75 MG (2-0-2) [Tafinlar]Drug

    Combination therapy is given in patients with BRAF V600E mutation.

Study groups in NCT04619316
Study groupRoleWhat they receive
BRAF wild typeOtherIn BRAF wild type patients trametinib 2mg (1-0-0) is applied daily over a time span of 3 weeks, then the effect is evaluated via 123I whole-body scintigraphy
Receives: Drug: Trametinib 2 MG [Mekinist]
BRAF V600E MutationOtherIn BRAF wild type patients trametinib 2mg (1-0-0) and dabrafenib 75mg (2-0-2) are applied daily over a time span of 3 weeks, then the effect is evaluated via 123I whole-body scintigraphy
Receives: Drug: Trametinib 2 MG [Mekinist] and Dabrafenib 75 MG (2-0-2) [Tafinlar]

What is being measured

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

  1. Proportion of patients with sufficiently increased tumoral iodine incorporation

    To determine the proportion of patients with BRAF WT RAIR thyroid cancer in which trametinib and the proportion of patients with BRAF MUT RAIR thyroid cancer in which the combination-therapy of dabrafenib and trametinib can increase tumoral iodine incorporation sufficiently.

    Measured: At the time point of 123I whole-body scintigraphy, 3 weeks after the start of redifferentiation therapy

Secondary outcomes (2)

  1. Changes in thyroglobulin levels

    Declines or increases in thyroglobulin levels after redifferentiation therapy

    Measured: Within 12 months after redifferentiation therapy

  2. The incidence and severity of adverse effects under trametinib (+dabrafenib) treatment

    The incidence and severity of adverse effects and necessary therapeutic measures are monitored pursuant to CTCAE 4.0 criteria

    Measured: Within 3 months

Timeline

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

  1. First posted6 Nov 2020
  2. Study start5 Feb 2018
  3. Primary completion31 Dec 2024 (estimated)
  4. Study completion31 Dec 2024 (estimated)

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
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
70 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04619316
Sponsor's protocol ID
ERRITI
Other IDs
2016-002941-49, Version 2.0, 2016
Acronym
ERRITI
Status last verified
Jun 2023
First submitted
1 Nov 2020
Last updated
22 Jun 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Trametinib 2 MG [Mekinist] and Trametinib 2 MG [Mekinist] and Dabrafenib 75 MG (2-0-2) [Tafinlar] in people with Metastatic Thyroid Cancer, run by University Hospital, Essen at 1 site in Germany.

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 26 inclusion and 17 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: status not confirmed, as of the sponsor's last update on 22 Jun 2023. 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 Germany. 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?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Wolfgang P Fendler, MD (+49 201 723 2032, wolfgang.fendler@uk-essen.de), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Proportion of patients with sufficiently increased tumoral iodine incorporation (time frame: At the time point of 123I whole-body scintigraphy, 3 weeks after the start of redifferentiation therapy). 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 NCT04619316.

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 Jun 2023.

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