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Thyroid CancerPhase 2NCT03630120

Adaptive Tyrosine Kinase Inhibitor (TKI) Therapy In Patients With Thyroid Cancer

A Phase 2 study testing Lenvatinib, Sorafenib and Cabozantinib in people with Thyroid Cancer and Thyroid Cancer, Medullary, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

Participants will have been diagnosed with advanced progressive thyroid cancer and are about to start treatment with a tyrosine kinase inhibitor (TKI). The purpose of this study is to evaluate the efficacy and tolerability of tyrosine kinase inhibitor therapy (Lenvatinib or Sorafenib for differentiated thyroid cancer… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Lenvatinib, Sorafenib and Cabozantinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
6 participants
Where
1 siteUnited States
Study dates
6 Aug 2018to 5 Dec 2019
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

  • 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.
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  • 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

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • H. Lee Moffitt Cancer Center and Research Institute

    Tampa, Florida, 33612

Other trials in United States

About this study

Official title: Adaptive Tyrosine Kinase Inhibitor Therapy In Patients With Advanced Progressive Thyroid Cancer

Participants will have been diagnosed with advanced progressive thyroid cancer and are about to start treatment with a tyrosine kinase inhibitor (TKI).

The purpose of this study is to evaluate the efficacy and tolerability of tyrosine kinase inhibitor therapy (Lenvatinib or Sorafenib for differentiated thyroid cancer [which includes papillary thyroid cancer, follicular thyroid cancer, and poorly differentiated thyroid cancer]; and Cabozantinib or Vandetanib for medullary thyroid cancer) through adaptive (intermittent) versus conventional (continuous) regimen.

Read the detailed description

Population: Patients with advanced progressive 131I-refractory DTC or MTC will be enrolled to this study. Forty-five patients responding to TKI therapy (defined as 50% drop in tumor marker level within the first two months of treatment) will be randomized to receive TKI therapy either through adaptive (intermittent) or conventional (continuous) regimen.

Being tested
Lenvatinib, Sorafenib, Cabozantinib, Vandetanib
Keywords
Thyroid disease, Tyrosine kinase inhibitor, TKI, Medullary thyroid cancer, DTC, Advanced thyroid cancer, Progressive thyroid cancer, MTC
Medical subject headings
Thyroid Neoplasms, Thyroid cancer, medullary, Thyroid Cancer, Papillary, Adenocarcinoma, Follicular, Thyroid Diseases, Carcinoma, Medullary

What participants receive

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

  • LenvatinibDrug

    Also called Lenvima®

    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.

  • SorafenibDrug

    Also called Nexavar®

    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.

  • CabozantinibDrug

    Also called Cabometyx®

    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.

  • VandetanibDrug

    Also called Caprelsa®

    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.

Study groups in NCT03630120
Study groupRoleWhat they receive
Standard of Care: DTCActive comparatorStandard of Care (SOC) TKI Therapy for Differentiated Thyroid Cancer (DTC): Lenvatinib + Sorafenib.
Receives: Drug: Lenvatinib; Drug: Sorafenib
Adaptive Care: DTCExperimentalSOC followed by Adaptive Care TKI Therapy for DTC Participants with >=50% drop: Lenvatinib + Sorafenib.
Receives: Drug: Lenvatinib; Drug: Sorafenib
Standard of Care: MTCActive comparatorStandard of Care (SOC) TKI Therapy for Medullary Thyroid Cancer: Cabozantinib + Vandetanib.
Receives: Drug: Cabozantinib; Drug: Vandetanib
Adaptive Care: MTCExperimentalSOC followed by Adaptive Care TKI Therapy for MTC Participants with >=50% drop: Cabozantinib + Vandetanib.
Receives: Drug: Cabozantinib; Drug: Vandetanib

What is being measured

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

  1. 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.

    Measured: 2 years

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

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

    Measured: 2 years

  3. 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.

    Measured: 2 years

Secondary outcomes (3)
  1. 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.

    Measured: Up to 48 months

  2. 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.

    Measured: Up to 48 months

  3. 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.

    Measured: Up to 48 months

Timeline

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

  1. First posted14 Aug 2018
  2. Study start6 Aug 2018
  3. Primary completion14 Nov 2019
  4. Study completion5 Dec 2019

Why it stopped: Lack of efficacy

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
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Investigator
Enrolment
6 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03630120
Sponsor's protocol ID
MCC-19442
Status last verified
Jul 2021
First submitted
10 Aug 2018
Last updated
14 Jul 2021
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Lenvatinib, Sorafenib and Cabozantinib in people with Thyroid Cancer and Thyroid Cancer, Medullary, run by H. Lee Moffitt Cancer Center and Research Institute 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 25 inclusion and 15 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: stopped early, as of the sponsor's last update on 14 Jul 2021. 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.

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 22 Jan 2021). 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?

Time to Tyrosine Kinase Inhibitor (TKI) Treatment Discontinuation Due to Progressive Disease (time frame: 2 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
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 14 Jul 2021.

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