Adaptive Tyrosine Kinase Inhibitor (TKI) Therapy In Patie... | NCT03630120

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Standard of Care: DTC	Active Comparator	Standard of Care (SOC) TKI Therapy for Differentiated Thyroid Cancer (DTC): Lenvatinib + Sorafenib.	Drug: Lenvatinib Drug: Sorafenib
Adaptive Care: DTC	Experimental	SOC followed by Adaptive Care TKI Therapy for DTC Participants with >=50% drop: Lenvatinib + Sorafenib.	Drug: Lenvatinib Drug: Sorafenib
Standard of Care: MTC	Active Comparator	Standard of Care (SOC) TKI Therapy for Medullary Thyroid Cancer: Cabozantinib + Vandetanib.	Drug: Cabozantinib Drug: Vandetanib
Adaptive Care: MTC	Experimental	SOC followed by Adaptive Care TKI Therapy for MTC Participants with >=50% drop: Cabozantinib + Vandetanib.	Drug: Cabozantinib Drug: Vandetanib

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Lenvatinib	Drug	Standard of Care: Lenvatinib 24 mg daily. All participants will start receiving standard of care treatment. Participants in the Adaptive Therapy regimen will receive TKI therapy in cycles: continuous treatment at the indicated dose until the patients' tumor marker (thyroglobulin in DTC or calcitonin in MTC patients) drops by ≥50% from the level at the time of enrollment ("baseline" level). A new cycle of TKI treatment will begin when/if the tumor marker increases to or above the "baseline" level.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Time to Tyrosine Kinase Inhibitor (TKI) Treatment Discontinuation Due to Progressive Disease	Median time-to-discontinuation (TTD) of treatment per study arm, due to Progressive Disease.	2 years
Time to Tyrosine Kinase Inhibitor (TKI) Treatment Discontinuation Due to Intolerability	Median time-to-discontinuation (TTD) of treatment per study arm, due to Intolerability.	2 years
Time to Tyrosine Kinase Inhibitor (TKI) Treatment Discontinuation Due to Disease Related Death	Median time-to-discontinuation (TTD) of treatment per study arm, due to Disease-related death at 2 years.	2 years

Secondary Outcomes

Measure	Description	Time Frame
Overall Response Rate (ORR)	The response rate will be estimated using binomial theory with Wilson's method for the 95% confidence interval. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter (LD). Stable Disease (SD): Neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum LD since the treatment started.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

All histologically or cytologically confirmed diagnosis of thyroid cancer, other than anaplastic or stromal-cell derived cancers.
Participants with differentiated thyroid cancers (DTC) must have negative thyroglobulin antibodies.
Measurable disease meeting the following criteria and confirmed by central radiographic review:
- At least 1 lesion of ≥ 1.0 centimeter (cm) in the longest diameter for a non- lymph node or ≥ 1.5 cm in the short-axis diameter for a lymph node which is serially measurable according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 using computerized tomography/magnetic resonance imaging (CT/MRI). If there is only one target lesion and it is a non-lymph node, it should have a longest diameter of ≥ 1.5 cm.
- Lesions that have had external beam radiotherapy (EBRT) or locoregional therapies such as radiofrequency (RF) ablation must show evidence of progressive disease (substantial size increase of ≥ 20%) within 12 months to be deemed a target lesion.
Participants must show evidence of disease progression comparing (a) scan in screening and (b) historical scan obtained within 12 months prior to signing informed consent, according to RECIST 1.1 assessed and confirmed by central radiographic review of CT and/or MRI scans.
Participants with DTC must not be eligible for possible curative surgery and must be radioiodine (RAI)-refractory / resistant as defined by at least one of the following:
- One or more measurable lesions that do not demonstrate iodine uptake on any radioiodine scan
- One or more measurable lesions that has progressed by RECIST 1.1 within 12 months of RAI therapy, despite demonstration of radioiodine avidity at the time of that treatment by pre- or post-treatment scanning.
- Disease progression in a patient that has received a cumulative activity of RAI of ≥ 550 millicuries (mCi) (22 gigabecquerels), with the last RAI dose administered at least 6 months prior to study entry.
- Otherwise deemed not a candidate for further RAI therapy by a multidisciplinary tumor board within 60 days of enrollment.
Participants with DTC must be receiving thyroxine suppression therapy and thyroid stimulating hormone (TSH) should not be elevated (TSH should be ≤ 0.1 mU/L).
"Measurable" tumor marker (non-stimulated thyroglobulin >10 ng/mL or CEA>10 ng/ML in patients with DTC; or serum basal calcitonin >10 pg/mL in patients with MTC)
Participants may have received prior multi-kinase targeted therapy except the TKI used in this trial. For example, patients getting Lenvatinib on this study may have been previously treated with Sorafenib, Vandetanib, Sunitinib, Pazopanib, etc. Each of the TKI targeted agents will be counted individually, regardless of the duration of its administration.
Participants with known brain metastases who have completed whole brain radiotherapy, stereotactic radiosurgery or complete surgical resection, will be eligible if they have remained clinically stable, asymptomatic for 30 days.
All chemotherapy or radiation related toxicities must have resolved to < Grade 2 severity per Common Terminology Criteria for Adverse Events (CTCAE v 5.0), except alopecia infertility, anemia (see separate criteria) and any toxicities deemed irreversible by the treating physician.
Participants must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 - 2.
Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP ≤ 150/90 mm Hg at screening and no change in antihypertensive medications within 1 week prior to Cycle 1/Day 1
Adequate renal function defined as calculated creatinine clearance ≥ 30 mL/min (using Cockcroft/Gault formula)
Adequate bone marrow function
Adequate liver function
Males or females age ≥ 18 years at the time of informed consent
Females must not be breastfeeding or pregnant at Screening or Baseline.
Males and females must follow all contraception guidelines as outlined in the protocol guidelines.
Voluntary agreement to provide written informed consent and the willingness and ability to comply with all aspects of the protocol

Exclusion Criteria:

Participants who have received any anticancer treatment (including Chinese herbal medicine specified for the treatment of tumor) within 21 days or any investigational agent within 30 days prior to the first dose of study drug. This does not apply to the use of TSH-suppressive thyroid hormone therapy.
Major surgery within 21 days prior to the first dose of study drug.
Palliative radiation therapy within 14 days prior to the first dose of study drug.
Participants having > 30 mg/mL urine protein on urine dipstick testing (Participants with urine protein < 1 g/24 hour (h) will be eligible).
Gastrointestinal malabsorption or any other condition that in the opinion of the investigator might affect the absorption of Lenvatinib, Sorafenib, Cabozantinib, or Vandetanib.
Significant cardiovascular impairment: history of (a) congestive heart failure greater than New York Heart association (NYHA) Class II, (b) unstable angina, (c) myocardial infarction, (d) stroke, or (e) cardiac arrhythmia associated with impairment within 6 months of the first dose of study drug.
Bleeding or thrombotic disorders (Treatment with low molecular weight heparin is allowed).
Radiographic evidence of major blood vessel invasion/infiltration.
Active hemoptysis (bright red blood of at least 0.5 teaspoon) within 21 days prior to the first dose of study drug.
Active infection (any infection requiring systemic treatment).
Active malignancy (except for DTC/MTC or definitively treated basal or squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix or bladder) within the past 24 months.
Known intolerance to any of the study drugs (or any of the excipients).
Any medical or other condition which, in the opinion of the investigator, would preclude participation in a clinical trial.
Females who are pregnant or breastfeeding.
Participants who are taking prohibited medications outlined in protocol documentation.

Name	Affiliation	Role
Christine H. Chung, M.D.	H. Lee Moffitt Cancer Center and Research Institute	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
H. Lee Moffitt Cancer Center and Research Institute		Tampa	Florida	33612	United States

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Standard of Care: DTC	Standard of Care (SOC) TKI Therapy for Differentiated Thyroid Cancer (DTC): Lenvatinib + Sorafenib.
FG001	Adaptive Care: DTC	SOC followed by Adaptive Care TKI Therapy for DTC Participants with >=50% drop: Lenvatinib + Sorafenib. Lenvatinib: Standard of Care: Lenvatinib 24 mg daily. All participants will start receiving standard of care treatment. Participants in the Adaptive Therapy regimen will receive TKI therapy in cycles: continuous treatment at the indicated dose until the patients' tumor marker (thyroglobulin in DTC or calcitonin in MTC patients) drops by ≥50% from the level at the time of enrollment ("baseline" level). A new cycle of TKI treatment will begin when/if the tumor marker increases to or above the "baseline" level. Sorafenib: Standard of Care: Sorafenib 400 mg twice daily. All participants will start receiving standard of care treatment. Participants in the Adaptive Therapy regimen will receive TKI therapy in cycles: continuous treatment at the indicated dose until the patients' tumor marker (thyroglobulin in DTC or calcitonin in MTC patients) drops by ≥50% from the level at the time of enrollment ("baseline" level). A new cycle of TKI treatment will begin when/if the tumor marker increases to or above the "baseline" level.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Jan 22, 2019

Arm/Group Information

ID	Title	Description
BG000	Standard of Care: DTC	Standard of Care (SOC) TKI Therapy for Differentiated Thyroid Cancer (DTC): Lenvatinib + Sorafenib. Lenvatinib: Standard of Care: Lenvatinib 24 mg daily. All participants will start receiving standard of care treatment. Participants in the Adaptive Therapy regimen will receive TKI therapy in cycles: continuous treatment at the indicated dose until the patients' tumor marker (thyroglobulin in DTC or calcitonin in MTC patients) drops by ≥50% from the level at the time of enrollment ("baseline" level). A new cycle of TKI treatment will begin when/if the tumor marker increases to or above the "baseline" level. Sorafenib: Standard of Care: Sorafenib 400 mg twice daily. All participants will start receiving standard of care treatment. Participants in the Adaptive Therapy regimen will receive TKI therapy in cycles: continuous treatment at the indicated dose until the patients' tumor marker (thyroglobulin in DTC or calcitonin in MTC patients) drops by ≥50% from the level at the time of enrollment ("baseline" level). A new cycle of TKI treatment will begin when/if the tumor marker increases to or above the "baseline" level.
BG001	Adaptive Care: DTC	SOC followed by Adaptive Care TKI Therapy for DTC Participants with >=50% drop: Lenvatinib + Sorafenib. Lenvatinib: Standard of Care: Lenvatinib 24 mg daily. All participants will start receiving standard of care treatment. Participants in the Adaptive Therapy regimen will receive TKI therapy in cycles: continuous treatment at the indicated dose until the patients' tumor marker (thyroglobulin in DTC or calcitonin in MTC patients) drops by ≥50% from the level at the time of enrollment ("baseline" level). A new cycle of TKI treatment will begin when/if the tumor marker increases to or above the "baseline" level. Sorafenib: Standard of Care: Sorafenib 400 mg twice daily. All participants will start receiving standard of care treatment. Participants in the Adaptive Therapy regimen will receive TKI therapy in cycles: continuous treatment at the indicated dose until the patients' tumor marker (thyroglobulin in DTC or calcitonin in MTC patients) drops by ≥50% from the level at the time of enrollment ("baseline" level). A new cycle of TKI treatment will begin when/if the tumor marker increases to or above the "baseline" level.
BG002	Standard of Care: MTC	Standard of Care (SOC) TKI Therapy for Medullary Thyroid Cancer: Cabozantinib + Vandetanib. Cabozantinib: Standard of Care: Cabozantinib 140 mg daily. All participants will start receiving standard of care treatment. Participants in the Adaptive Therapy regimen will receive TKI therapy in cycles: continuous treatment at the indicated dose until the patients' tumor marker (thyroglobulin in DTC or calcitonin in MTC patients) drops by ≥50% from the level at the time of enrollment ("baseline" level). A new cycle of TKI treatment will begin when/if the tumor marker increases to or above the "baseline" level. Vandetanib: Standard of Care: Vandetanib 300 mg daily. All participants will start receiving standard of care treatment. Participants in the Adaptive Therapy regimen will receive TKI therapy in cycles: continuous treatment at the indicated dose until the patients' tumor marker (thyroglobulin in DTC or calcitonin in MTC patients) drops by ≥50% from the level at the time of enrollment ("baseline" level). A new cycle of TKI treatment will begin when/if the tumor marker increases to or above the "baseline" level.
BG003	Adaptive Care: MTC	SOC followed by Adaptive Care TKI Therapy for MTC Participants with >=50% drop: Cabozantinib + Vandetanib. Cabozantinib: Standard of Care: Cabozantinib 140 mg daily. All participants will start receiving standard of care treatment. Participants in the Adaptive Therapy regimen will receive TKI therapy in cycles: continuous treatment at the indicated dose until the patients' tumor marker (thyroglobulin in DTC or calcitonin in MTC patients) drops by ≥50% from the level at the time of enrollment ("baseline" level). A new cycle of TKI treatment will begin when/if the tumor marker increases to or above the "baseline" level. Vandetanib: Standard of Care: Vandetanib 300 mg daily. All participants will start receiving standard of care treatment. Participants in the Adaptive Therapy regimen will receive TKI therapy in cycles: continuous treatment at the indicated dose until the patients' tumor marker (thyroglobulin in DTC or calcitonin in MTC patients) drops by ≥50% from the level at the time of enrollment ("baseline" level). A new cycle of TKI treatment will begin when/if the tumor marker increases to or above the "baseline" level.
BG004	Total	Total of all reporting groups

Units	Counts
Participants	BG0002 BG0012 BG0021 BG0031 BG0046

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Time to Tyrosine Kinase Inhibitor (TKI) Treatment Discontinuation Due to Progressive Disease

Median time-to-discontinuation (TTD) of treatment per study arm, due to Progressive Disease.

Data not collected. Only 3 participants remained on study treatment, and none for full length of trial.

Posted

2 years

ID	Title	Description
OG000	Standard of Care: DTC	Standard of Care (SOC) TKI Therapy for Differentiated Thyroid Cancer (DTC): Lenvatinib + Sorafenib. Lenvatinib: Standard of Care: Lenvatinib 24 mg daily. All participants will start receiving standard of care treatment. Participants in the Adaptive Therapy regimen will receive TKI therapy in cycles: continuous treatment at the indicated dose until the patients' tumor marker (thyroglobulin in DTC or calcitonin in MTC patients) drops by ≥50% from the level at the time of enrollment ("baseline" level). A new cycle of TKI treatment will begin when/if the tumor marker increases to or above the "baseline" level. Sorafenib: Standard of Care: Sorafenib 400 mg twice daily. All participants will start receiving standard of care treatment. Participants in the Adaptive Therapy regimen will receive TKI therapy in cycles: continuous treatment at the indicated dose until the patients' tumor marker (thyroglobulin in DTC or calcitonin in MTC patients) drops by ≥50% from the level at the time of enrollment ("baseline" level). A new cycle of TKI treatment will begin when/if the tumor marker increases to or above the "baseline" level.
OG001	Adaptive Care: DTC	SOC followed by Adaptive Care TKI Therapy for DTC Participants with >=50% drop: Lenvatinib + Sorafenib. Lenvatinib: Standard of Care: Lenvatinib 24 mg daily. All participants will start receiving standard of care treatment. Participants in the Adaptive Therapy regimen will receive TKI therapy in cycles: continuous treatment at the indicated dose until the patients' tumor marker (thyroglobulin in DTC or calcitonin in MTC patients) drops by ≥50% from the level at the time of enrollment ("baseline" level). A new cycle of TKI treatment will begin when/if the tumor marker increases to or above the "baseline" level. Sorafenib: Standard of Care: Sorafenib 400 mg twice daily. All participants will start receiving standard of care treatment. Participants in the Adaptive Therapy regimen will receive TKI therapy in cycles: continuous treatment at the indicated dose until the patients' tumor marker (thyroglobulin in DTC or calcitonin in MTC patients) drops by ≥50% from the level at the time of enrollment ("baseline" level). A new cycle of TKI treatment will begin when/if the tumor marker increases to or above the "baseline" level.
OG002	Standard of Care: MTC	Standard of Care (SOC) TKI Therapy for Medullary Thyroid Cancer: Cabozantinib + Vandetanib. Cabozantinib: Standard of Care: Cabozantinib 140 mg daily. All participants will start receiving standard of care treatment. Participants in the Adaptive Therapy regimen will receive TKI therapy in cycles: continuous treatment at the indicated dose until the patients' tumor marker (thyroglobulin in DTC or calcitonin in MTC patients) drops by ≥50% from the level at the time of enrollment ("baseline" level). A new cycle of TKI treatment will begin when/if the tumor marker increases to or above the "baseline" level. Vandetanib: Standard of Care: Vandetanib 300 mg daily. All participants will start receiving standard of care treatment. Participants in the Adaptive Therapy regimen will receive TKI therapy in cycles: continuous treatment at the indicated dose until the patients' tumor marker (thyroglobulin in DTC or calcitonin in MTC patients) drops by ≥50% from the level at the time of enrollment ("baseline" level). A new cycle of TKI treatment will begin when/if the tumor marker increases to or above the "baseline" level.
OG003	Adaptive Care: MTC	SOC followed by Adaptive Care TKI Therapy for MTC Participants with >=50% drop: Cabozantinib + Vandetanib. Cabozantinib: Standard of Care: Cabozantinib 140 mg daily. All participants will start receiving standard of care treatment. Participants in the Adaptive Therapy regimen will receive TKI therapy in cycles: continuous treatment at the indicated dose until the patients' tumor marker (thyroglobulin in DTC or calcitonin in MTC patients) drops by ≥50% from the level at the time of enrollment ("baseline" level). A new cycle of TKI treatment will begin when/if the tumor marker increases to or above the "baseline" level. Vandetanib: Standard of Care: Vandetanib 300 mg daily. All participants will start receiving standard of care treatment. Participants in the Adaptive Therapy regimen will receive TKI therapy in cycles: continuous treatment at the indicated dose until the patients' tumor marker (thyroglobulin in DTC or calcitonin in MTC patients) drops by ≥50% from the level at the time of enrollment ("baseline" level). A new cycle of TKI treatment will begin when/if the tumor marker increases to or above the "baseline" level.

Units	Counts
Participants	OG0000 OG0010 OG0020 OG003

Primary

Time to Tyrosine Kinase Inhibitor (TKI) Treatment Discontinuation Due to Intolerability

Median time-to-discontinuation (TTD) of treatment per study arm, due to Intolerability.

Data not collected. Only 3 participants remained on study treatment, and none for full length of trial.

Posted

2 years

ID	Title	Description
OG000	Standard of Care: DTC	Standard of Care (SOC) TKI Therapy for Differentiated Thyroid Cancer (DTC): Lenvatinib + Sorafenib. Lenvatinib: Standard of Care: Lenvatinib 24 mg daily. All participants will start receiving standard of care treatment. Participants in the Adaptive Therapy regimen will receive TKI therapy in cycles: continuous treatment at the indicated dose until the patients' tumor marker (thyroglobulin in DTC or calcitonin in MTC patients) drops by ≥50% from the level at the time of enrollment ("baseline" level). A new cycle of TKI treatment will begin when/if the tumor marker increases to or above the "baseline" level. Sorafenib: Standard of Care: Sorafenib 400 mg twice daily. All participants will start receiving standard of care treatment. Participants in the Adaptive Therapy regimen will receive TKI therapy in cycles: continuous treatment at the indicated dose until the patients' tumor marker (thyroglobulin in DTC or calcitonin in MTC patients) drops by ≥50% from the level at the time of enrollment ("baseline" level). A new cycle of TKI treatment will begin when/if the tumor marker increases to or above the "baseline" level.
OG001	Adaptive Care: DTC

Primary

Time to Tyrosine Kinase Inhibitor (TKI) Treatment Discontinuation Due to Disease Related Death

Median time-to-discontinuation (TTD) of treatment per study arm, due to Disease-related death at 2 years.

Data not collected. Only 3 participants remained on study treatment, and none for full length of trial.

Posted

2 years

ID	Title	Description
OG000	Standard of Care: DTC	Standard of Care (SOC) TKI Therapy for Differentiated Thyroid Cancer (DTC): Lenvatinib + Sorafenib. Lenvatinib: Standard of Care: Lenvatinib 24 mg daily. All participants will start receiving standard of care treatment. Participants in the Adaptive Therapy regimen will receive TKI therapy in cycles: continuous treatment at the indicated dose until the patients' tumor marker (thyroglobulin in DTC or calcitonin in MTC patients) drops by ≥50% from the level at the time of enrollment ("baseline" level). A new cycle of TKI treatment will begin when/if the tumor marker increases to or above the "baseline" level. Sorafenib: Standard of Care: Sorafenib 400 mg twice daily. All participants will start receiving standard of care treatment. Participants in the Adaptive Therapy regimen will receive TKI therapy in cycles: continuous treatment at the indicated dose until the patients' tumor marker (thyroglobulin in DTC or calcitonin in MTC patients) drops by ≥50% from the level at the time of enrollment ("baseline" level). A new cycle of TKI treatment will begin when/if the tumor marker increases to or above the "baseline" level.
OG001	Adaptive Care: DTC

Secondary

Overall Response Rate (ORR)

The response rate will be estimated using binomial theory with Wilson's method for the 95% confidence interval. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter (LD). Stable Disease (SD): Neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum LD since the treatment started.

Data not collected. Only 3 participants remained on study treatment, and none for full length of trial.

Posted

Up to 48 months

ID	Title	Description
OG000	Standard of Care: DTC	Standard of Care (SOC) TKI Therapy for Differentiated Thyroid Cancer (DTC): Lenvatinib + Sorafenib. Lenvatinib: Standard of Care: Lenvatinib 24 mg daily. All participants will start receiving standard of care treatment. Participants in the Adaptive Therapy regimen will receive TKI therapy in cycles: continuous treatment at the indicated dose until the patients' tumor marker (thyroglobulin in DTC or calcitonin in MTC patients) drops by ≥50% from the level at the time of enrollment ("baseline" level). A new cycle of TKI treatment will begin when/if the tumor marker increases to or above the "baseline" level. Sorafenib: Standard of Care: Sorafenib 400 mg twice daily. All participants will start receiving standard of care treatment. Participants in the Adaptive Therapy regimen will receive TKI therapy in cycles: continuous treatment at the indicated dose until the patients' tumor marker (thyroglobulin in DTC or calcitonin in MTC patients) drops by ≥50% from the level at the time of enrollment ("baseline" level). A new cycle of TKI treatment will begin when/if the tumor marker increases to or above the "baseline" level.

Secondary

Progression-free Survival (PFS)

The median progression-free survival rates will be estimated from the Kaplan-Meier curve with the 95% confidence interval obtained from Greenwood's formula. Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

Data not collected. Only 3 participants remained on study treatment, and none for full length of trial.

Posted

Up to 48 months

ID	Title	Description
OG000	Standard of Care: DTC	Standard of Care (SOC) TKI Therapy for Differentiated Thyroid Cancer (DTC): Lenvatinib + Sorafenib. Lenvatinib: Standard of Care: Lenvatinib 24 mg daily. All participants will start receiving standard of care treatment. Participants in the Adaptive Therapy regimen will receive TKI therapy in cycles: continuous treatment at the indicated dose until the patients' tumor marker (thyroglobulin in DTC or calcitonin in MTC patients) drops by ≥50% from the level at the time of enrollment ("baseline" level). A new cycle of TKI treatment will begin when/if the tumor marker increases to or above the "baseline" level. Sorafenib: Standard of Care: Sorafenib 400 mg twice daily. All participants will start receiving standard of care treatment. Participants in the Adaptive Therapy regimen will receive TKI therapy in cycles: continuous treatment at the indicated dose until the patients' tumor marker (thyroglobulin in DTC or calcitonin in MTC patients) drops by ≥50% from the level at the time of enrollment ("baseline" level). A new cycle of TKI treatment will begin when/if the tumor marker increases to or above the "baseline" level.

Secondary

Overall Survival (OS)

The median overall survival rates will be estimated from the Kaplan-Meier curve with the 95% confidence interval obtained from Greenwood's formula.

Data not collected. Only 3 participants remained on study treatment, and none for full length of trial.

Posted

Up to 48 months

ID	Title	Description
OG000	Standard of Care: DTC	Standard of Care (SOC) TKI Therapy for Differentiated Thyroid Cancer (DTC): Lenvatinib + Sorafenib. Lenvatinib: Standard of Care: Lenvatinib 24 mg daily. All participants will start receiving standard of care treatment. Participants in the Adaptive Therapy regimen will receive TKI therapy in cycles: continuous treatment at the indicated dose until the patients' tumor marker (thyroglobulin in DTC or calcitonin in MTC patients) drops by ≥50% from the level at the time of enrollment ("baseline" level). A new cycle of TKI treatment will begin when/if the tumor marker increases to or above the "baseline" level. Sorafenib: Standard of Care: Sorafenib 400 mg twice daily. All participants will start receiving standard of care treatment. Participants in the Adaptive Therapy regimen will receive TKI therapy in cycles: continuous treatment at the indicated dose until the patients' tumor marker (thyroglobulin in DTC or calcitonin in MTC patients) drops by ≥50% from the level at the time of enrollment ("baseline" level). A new cycle of TKI treatment will begin when/if the tumor marker increases to or above the "baseline" level.
OG001	Adaptive Care: DTC

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Standard of Care: DTC	Standard of Care (SOC) TKI Therapy for Differentiated Thyroid Cancer (DTC): Lenvatinib + Sorafenib. Lenvatinib: Standard of Care: Lenvatinib 24 mg daily. All participants will start receiving standard of care treatment. Participants in the Adaptive Therapy regimen will receive TKI therapy in cycles: continuous treatment at the indicated dose until the patients' tumor marker (thyroglobulin in DTC or calcitonin in MTC patients) drops by ≥50% from the level at the time of enrollment ("baseline" level). A new cycle of TKI treatment will begin when/if the tumor marker increases to or above the "baseline" level. Sorafenib: Standard of Care: Sorafenib 400 mg twice daily. All participants will start receiving standard of care treatment. Participants in the Adaptive Therapy regimen will receive TKI therapy in cycles: continuous treatment at the indicated dose until the patients' tumor marker (thyroglobulin in DTC or calcitonin in MTC patients) drops by ≥50% from the level at the time of enrollment ("baseline" level). A new cycle of TKI treatment will begin when/if the tumor marker increases to or above the "baseline" level.	0	2	2	1	2
EG001	Adaptive Care: DTC	SOC followed by Adaptive Care TKI Therapy for DTC Participants with >=50% drop: Lenvatinib + Sorafenib. Lenvatinib: Standard of Care: Lenvatinib 24 mg daily. All participants will start receiving standard of care treatment. Participants in the Adaptive Therapy regimen will receive TKI therapy in cycles: continuous treatment at the indicated dose until the patients' tumor marker (thyroglobulin in DTC or calcitonin in MTC patients) drops by ≥50% from the level at the time of enrollment ("baseline" level). A new cycle of TKI treatment will begin when/if the tumor marker increases to or above the "baseline" level. Sorafenib: Standard of Care: Sorafenib 400 mg twice daily. All participants will start receiving standard of care treatment. Participants in the Adaptive Therapy regimen will receive TKI therapy in cycles: continuous treatment at the indicated dose until the patients' tumor marker (thyroglobulin in DTC or calcitonin in MTC patients) drops by ≥50% from the level at the time of enrollment ("baseline" level). A new cycle of TKI treatment will begin when/if the tumor marker increases to or above the "baseline" level.	1	2	2	0	2
EG002	Standard of Care: MTC	Standard of Care (SOC) TKI Therapy for Medullary Thyroid Cancer: Cabozantinib + Vandetanib. Cabozantinib: Standard of Care: Cabozantinib 140 mg daily. All participants will start receiving standard of care treatment. Participants in the Adaptive Therapy regimen will receive TKI therapy in cycles: continuous treatment at the indicated dose until the patients' tumor marker (thyroglobulin in DTC or calcitonin in MTC patients) drops by ≥50% from the level at the time of enrollment ("baseline" level). A new cycle of TKI treatment will begin when/if the tumor marker increases to or above the "baseline" level. Vandetanib: Standard of Care: Vandetanib 300 mg daily. All participants will start receiving standard of care treatment. Participants in the Adaptive Therapy regimen will receive TKI therapy in cycles: continuous treatment at the indicated dose until the patients' tumor marker (thyroglobulin in DTC or calcitonin in MTC patients) drops by ≥50% from the level at the time of enrollment ("baseline" level). A new cycle of TKI treatment will begin when/if the tumor marker increases to or above the "baseline" level.	1	1	1	0	1
EG003	Adaptive Care: MTC	SOC followed by Adaptive Care TKI Therapy for MTC Participants with >=50% drop: Cabozantinib + Vandetanib. Cabozantinib: Standard of Care: Cabozantinib 140 mg daily. All participants will start receiving standard of care treatment. Participants in the Adaptive Therapy regimen will receive TKI therapy in cycles: continuous treatment at the indicated dose until the patients' tumor marker (thyroglobulin in DTC or calcitonin in MTC patients) drops by ≥50% from the level at the time of enrollment ("baseline" level). A new cycle of TKI treatment will begin when/if the tumor marker increases to or above the "baseline" level. Vandetanib: Standard of Care: Vandetanib 300 mg daily. All participants will start receiving standard of care treatment. Participants in the Adaptive Therapy regimen will receive TKI therapy in cycles: continuous treatment at the indicated dose until the patients' tumor marker (thyroglobulin in DTC or calcitonin in MTC patients) drops by ≥50% from the level at the time of enrollment ("baseline" level). A new cycle of TKI treatment will begin when/if the tumor marker increases to or above the "baseline" level.	1	1	1	0	1

ID	Term
D013964	Thyroid Neoplasms
C536914	Thyroid cancer, medullary
D000077273	Thyroid Cancer, Papillary
D018263	Adenocarcinoma, Follicular
D013959	Thyroid Diseases
D018276	Carcinoma, Medullary

ID	Term
D004701	Endocrine Gland Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D006258	Head and Neck Neoplasms
D004700	Endocrine System Diseases
D000231	Adenocarcinoma, Papillary
D000230	Adenocarcinoma
D002277	Carcinoma
D009375	Neoplasms, Glandular and Epithelial
D009370	Neoplasms by Histologic Type
D018278	Carcinoma, Neuroendocrine
D018358	Neuroendocrine Tumors
D017599	Neuroectodermal Tumors
D009373	Neoplasms, Germ Cell and Embryonal
D018299	Neoplasms, Ductal, Lobular, and Medullary
D009380	Neoplasms, Nerve Tissue

ID	Term
C531958	lenvatinib
D000077157	Sorafenib
C558660	cabozantinib
C452423	vandetanib

ID	Term
D010671	Phenylurea Compounds
D014508	Urea
D000577	Amides
D009930	Organic Chemicals
D001555	Benzene Derivatives
D006841	Hydrocarbons, Aromatic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D009536	Niacinamide
D009539	Nicotinic Acids
D000147	Acids, Heterocyclic
D006571	Heterocyclic Compounds
D011725	Pyridines
D006573	Heterocyclic Compounds, 1-Ring