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

NCT04619316 | Unknown Phase 2

• 3 other identifiers: ERRITI2016-002941-49Version 2.0
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Metastatic Thyroid Cancer

Outcome Measures

Primary Outcomes (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.

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

Secondary Outcomes (2)

• Changes in thyroglobulin levels

  Within 12 months after redifferentiation therapy

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

  Within 3 months

Study Arms (2)

BRAF wild type

OTHER

In 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

Drug: Trametinib 2 MG [Mekinist]

BRAF V600E Mutation

OTHER

In 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

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

Interventions

Trametinib 2 MG [Mekinist] DRUG

Monotherapy with Trametinib is given in patients with BRAF wildtype.

BRAF wild type

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

Combination therapy is given in patients with BRAF V600E mutation.

BRAF V600E Mutation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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).
• 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.

Sponsors & Collaborators

• University Hospital, Essen: lead

Study Sites (1)

Manuel M. Weber

Essen, North Rhine-Westphalia, 45147, Germany

RECRUITING

MeSH Terms

Conditions

Thyroid Neoplasms

Interventions

trametinib; dabrafenib

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Endocrine System Diseases; Thyroid Diseases

Study Officials

• Wolfgang P Fendler, MD

  Department of Nuclear Medicine, Essen University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 1, 2020
• First Posted: November 6, 2020
• Study Start: February 5, 2018
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2024
• Last Updated: June 22, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)