Neoplasms

Gland and Hormone Related Diseases

All Conditions

Rare Diseases

Thyroid Neoplasms

Thyroid Cancer, Papillary

Thyroid Diseases

Adenocarcinoma, Follicular

Endocrine System Diseases

Endocrine Gland Neoplasms

Head and Neck Neoplasms

Papillary Thyroid Carcinoma

Thyroid Cancer, Follicular

Thyroid Cancer, Medullary

Hurthle Cell Thyroid Cancer

All Drugs and Chemicals

Imetelstat

Motesanib diphosphate

Protein Kinase Inhibitors

Enzyme Inhibitors

AMG 706

The purpose of the study is to determine if AMG 706 will have clinically meaningful anti-tumor activity in subjects with locally advanced or metastatic thyroid cancer who are not candidates for radioactive iodine therapy or local therapies.

A Phase 2, Open-label Study of AMG 706 to Treat Subjects With Locally Advanced or Metastatic Thyroid Cancer

Amgen

Adenocarcinoma

Adenocarcinoma, Papillary

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Antineoplastic Agents

Micronutrients

Anti-Infective Agents

Sunitinib

Iodine

Cadexomer iodine

Angiogenesis Inhibitors

Growth Inhibitors

Sutent 37.5 mg/day will be given orally after radioactive iodine therapy. Total time of Sutent drug administration will be 52 weeks, absent unacceptable toxicity or disease progression. Sutent is supplied as 12.5mg and 25 mg tablets. Patients are to swallow the tablets whole with approximately 250 ml (8 oz.) of water, fasting each morning. Patients will be given monthly calendars (patient diaries) to document the time when the Sutent pills are taken. At monthly visits, patients will bring back this record and the drug bottles.

SU011248, Sutent

Kenneth D Burman, MD

This study is comparing a drug called Sutent with standard of care treatment for people with advanced thyroid cancer. Because advanced thyroid cancer is becoming increasingly common and effective treatment options are limited, new therapies are desperately needed.

This study is designed to see if Sutent following therapy with radioactive iodine will target cancer cells and delay disease progression better than standard therapy alone. Newly diagnosed patients, who are scheduled to receive radioactive iodine as part of their standard care are possible candidates. By entering into this study, participants agree to take oral Sutent for approximately two years after completing standard therapy. During this time, study participants will be followed closely by their doctor.

This is a two-stage, phase II, single center, targeted therapy trial enrolling patients with stage 2 (for patients younger than 45 years of age), 3 or 4 differentiated thyroid cancer. The primary objective is to assess progression free survival in this population. Sutent will be given orally at 37.5mg daily for two (2) year, or 26 cycles. Each treatment cycle will consist of 28 days. Upon treatment discontinuation, patients will be followed for survival. The frequency and type of survival follow-up assessments performed will be at the discretion of the treating physician.

Sutent Adjunctive Treatment of Differentiated Thyroid Cancer

Progressive disease (PD) is defined as unequivocal progression of existing non-target lesions, or the appearance of 1 or more new lesions. Disease progression is accessed using the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).

Overall survival is defined as the time from the start of treatment to the time to death from any cause or final data collection, whatever happens first.

Pfizer

Medstar Health Research Institute

Sutent 37.5 mg/day will be given orally.

SU011248, Sutent: Sutent 37.5 mg/day will be given orally after radioactive iodine therapy. Total time of Sutent drug administration will be 52 weeks, absent unacceptable toxicity or disease progression. Sutent is supplied as 12.5mg and 25 mg tablets. Patients are to swallow the tablets whole with approximately 250 ml (8 oz.) of water, fasting each morning. Patients will be given monthly calendars (patient diaries) to document the time when the Sutent pills are taken. At monthly visits, patients will bring back this record and the drug bottles.

Treatment Arm - Sutent

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

Dr Kenneth D. Burman

Progression Free Survival

Overall Survival

Overall Study

Symptoms and General Pathology

Neoplasm Metastasis

Antirheumatic Agents

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Aldesleukin

Immunomodulating Agents

Carbamide Peroxide

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Anti-HIV Agents

Anti-Retroviral Agents

Antiviral Agents

All patients will receive a non-myeloablative lymphocyte depleting preparative regimen of cyclophosphamide and fludarabine followed by antithyroglobulin mTCR PBL and aldesleukin.

Aldeskeukin 720,000 IU/kg IV over 15 minutes approximately every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 3 days (maximum of 9 doses).

Day -7 to -3:Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.

Days -7 and -6:Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hour.

On day 0, one to four days after last dose of fludarabine, cells will be infused intravenously (IV) over 20 to 30 minutes.

Anti-Thyroglobulin mTCR PBL

James C Yang, M.D.

Background

The NCI Surgery Branch has developed an experimental therapy for treating patient with metastatic thyroid cancer that involves taking white blood cells from the patient, growing them in the laboratory in large numbers, genetically modifying these specific cells with a type of virus (retrovirus) to attack only the tumor cells, and then giving the cells back to the patient. This type of therapy is called gene transfer. In this protocol, we are modifying the patient s white blood cells with a retrovirus that has the gene for anti-thyroglobulin incorporated in the retrovirus.

Objectives:

The purpose of this study is to see if these tumor fighting cells (genetically modified cells) that express the receptor for the thyroglobulin molecule on their surface can cause thyroid tumors to shrink and to see if this treatment is safe.

Eligibility:

\<TAB\>Adults 18 and older with thyroid cancer that has the thyroglobulin molecule on tumor surfaces

Design:

\<TAB\>Work up stage: Patients will be seen as an outpatient at the NIH clinical Center and undergo a history and physical examination, scans, x-rays, lab tests, and other tests as needed

\<TAB\>Leukapheresis: If the patients meet all of the requirements for the study they will undergo leukapheresis to obtain white blood cells to make the anti- thyroglobulin cells. {Leukapheresis is a common procedure, which removes only the white blood cells from the patient.}

\<TAB\>Treatment: Once their cells have grown, the patients will be admitted to the hospital for the conditioning chemotherapy, the anti-thyroglobulin cells and aldesleukin. They will stay in the hospital for about 4 weeks for the treatment.

Follow up:

Patients will return to the clinic for a physical exam, review of side effects, lab tests, and scans about every 1-3 months for the first year, and then every 6 months to 1 year as long as their tumors are shrinking. Follow up visits take up to 2 days.

Background:

* We generated a murine T-cell receptor (mTCR) that recognizes human thyroglobulin (hTG) in the context of HLA-A0201 and constructed a single retroviral vector that contains its alpha and beta chains and will confer hTG recognition to HLA-A0201+ PBL on transduction.
* In co-cultures with HLA-A0201+, hTG+ target cells, anti-TG mTCR transduced T cells secrete significant amounts of IFN- \>= with high specificity.

Objectives:

Primary objectives:

* To determine the safety of administering PBL transduced with this anti-TG mTCR in concert with preparative lymphodepletion and high dose interleukin-2 (IL-2; aldesleukin).
* Determine if these mTCR-transduced PBL can mediate the regression of TG-expressing tumors.

Eligibility:

Patients who are HLA-A\*0201 positive and 18 years of age or older must have

-Advanced TG-expressing thyroid cancer (including those with bone-only disease) which has progressed after surgery (if indicated) and radioiodine ablation

Patients may not have:

-Contraindications for high dose aldesleukin administration.

Design:

* PBMC obtained by leukapheresis will be cultured in the presence of anti-CD3 (OKT3) and aldesleukin in order to stimulate T-cell growth.
* Transduction is initiated by exposure of these cells to retroviral vector supernatant containing replication-incompetent virus encoding the anti-TG mTCR.
* All patients will receive a non-myeloablative lymphocyte depleting preparative regimen of cyclophosphamide and fludarabine.
* On day 0 patients will receive their PBL transduced with the anti-TG mTCR and then begin high dose aldesleukin.
* A complete evaluation of evaluable lesions will be conducted approximately 4-6 weeks after treatment.
* The study will be conducted using a Phase I/II optimal design.
* The objective will be to determine if the combination of high dose aldesleukin, lymphocyte depleting chemotherapy, and anti-TG mTCR-gene engineered lymphocytes is able to be associated with a clinical response rate that can rule out 5% (p0=0.05) in favor of a modest 20% PR + CR rate (p1=0.20).
* A total of up to 68 patients may be required; approximately 25 patients in the phase I portion of the study and 43 (41, plus an allowance of up to 2 non-evaluable) patients in the phase II portion of the study.

Administering Peripheral Blood Lymphocytes Transduced With a Murine T-Cell Receptor Recognizing Human Thyroglobulin to People With Thyroglobulin Expressing Thyroid Cancer

Phase I/II Study Administering Peripheral Blood Lymphocytes Transduced With a Murine T-Cell Receptor Recognizing Human Thyroglobulin to Patients With Thyroglobulin Expressing Thyroid Cancer

National Cancer Institute (NCI)

The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits.

* Participants will be treated with Selpercatinib for 4 weeks.
* In the fourth week of treatment, participants will receive a therapeutic dose of I-131.

  * Those participants in whom radioiodine uptake has been restored may be offered a second 4-week course of selpercatinib plus I-131 treatment

Selpercatinib Oral, twice daily during initial treatment period (28 Days). A second course of selpercatinib if the participant is demonstrating clinical benefit to the initial course selpercatinib and deemed clinically appropriate by the treating investigator

Selpercatinib

I-131, oral, is a standard treatment for all types of follicular-derived thyroid cancers, except anaplastic thyroid cancer

Sodium Iodine I-131

RhTSH injection, dosage per protocol, timing per protocol during the initial treatment period per standard of care.

Participants may receive a second course of rhTSH if the participant is demonstrating clinical benefit to the initial course rhTSH and deemed clinically appropriate by the treating investigator.

rhTSH

Lori J. Wirth, MD

Lori J Wirth, MD

This research is being done to determine the efficacy of selpercatinib to restore radioactive iodine (I-131) uptake and allow for I-131 treatment in people with RET fusion-positive radioiodine-refractory thyroid cancer.

This research study involves the study drug selpercatinib in combination with standard of care treatments, I-131 and thyrotropin alfa (rhTSH).

The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits.

* This research study involves the study drug selpercatinib in combination with standard of care treatments, I-131 and thyrotropin alfa (rhTSH). Participants receive study treatment for as long as the disease does not worsen (disease progression) for approximately 1 month for up to two courses of treatment, if participants do not experience any unacceptable side effects, and/or until withdrawal of consent.
* Participants will be followed for 2 years from the date of study registration.
* It is expected that about 30 people will take part in this research study/
* This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. "Investigational" means that the drug is being studied.

  * The U.S. FDA has approved selpercatinib, I-131 and rhTSH as a treatment option for this disease.
  * The combination therapy is investigational as it has not been approved to treat this disease.
* Selpercatinib, I-131 and rhTSH are standard of care treatment options for thyroid cancer. Selpercatinib is a small molecule designed to block the active RET signaling.

Restor. I-131 Upt. + Selpercatinib in RET F-P RAI-R TC

Restoration of Radioiodine Uptake With Selpercatinib in RET Fusion-Positive Radioiodine-Refractory Thyroid Cancer: A Phase 2 Study Performed in Collaboration With the International Thyroid Oncology Group (ITOG)

The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to Sponsor Investigator or designee. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

RECIST v1.1 or Nies criteria in adolescents without RECIST-measurable disease The primary endpoint is best overall response (ORR) (CR and PR) at 6 months. The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started).Complete Response (CR) Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters

The safety profile of selpercatinib plus I-131 treatment in this patient population, will be evaluated by assessing by the incidence of treatment-related adverse events per Common Terminology Criteria for Adverse Events (CTCAE) v5.0

The estimated rate of restoration of I-131 uptake in patients with RAI-refractory RET fusion-positive thyroid cancer treated with selpercatinib will be estimated by determining the rate of positive whole body scans performed after I-131 administration.

The estimated best thyroglobulin biochemical response rates will be determined by comparing serial serum thyroglobulin levels taken every 3 months following treatment to that of the pretreatment baseline level in participants with measurable serum thyroglobulin. Best biochemical response is defined as follows: equals normalization of thyroglobulin level; partial response equals

≥50% decrease from baseline thyroglobulin; stable disease equals \<50% decrease or increase from baseline; and biochemical progression equals ≥50% increase from baseline (each maintained for at least 4 weeks).

Kaplan-Meier Method Time to subsequent systemic treatment in patients with RET fusion-positive RAIrefractory thyroid cancer will also be estimated.

The structural, biochemical, and overall response rate perl \[19\] for adolescent patients who enroll without measurable disease will be reported descriptively for adolescents who enroll without RECIST measurable disease.

Eli Lilly and Company

Massachusetts General Hospital

Principal Investigator

Carcinoma, Papillary

Neoplasms, Squamous Cell

Durvalumab

Tremelimumab

Antineoplastic Agents, Immunological

Durvalumab 1500 mg plus tremelimumab 75 mg every 4 weeks up to 4 cycles followed by durvalumab 1500 mg every 4 weeks until disease progression, unacceptable toxicity or patients' decision.

Subjects will be allocated in each primary tumor cohort to receive durvalumab 1500 mg every 4 weeks (Q4W) plus tremelimumab 75 mg Q4W for up to 4 doses during the first 4 cycles of combined therapy. After the first 4 cycles (or before is tremelimumab is stopped due to toxicity), patients will continue to receive durvalumab 1500 mg Q4W until disease progression or unacceptable toxicity. Cycles are defined by 4 weeks or 28 days.

Jaume Capdevila, M.D., Ph.D.

This is a prospective, multi-centre, open label, stratified, exploratory phase II study evaluating the efficacy and safety of durvalumab plus tremelimumab in different cohorts of patients with thyroid cancers.

* Cohort 1: Advanced, radioiodine-refractory differentiated thyroid carcinoma, including papillary, follicular, Hürtle. Cell and poorly-differentiated thyroid carcinoma (DTC).
* Cohort 2: Advanced medullary thyroid carcinoma (MTC).
* Cohort 3: Advanced anaplastic thyroid cancer (ATC).

Durvalumab Plus Tremelimumab for the Treatment of Patients With Progressive, Refractory Advanced Thyroid Carcinoma -The DUTHY Trial

A Phase II Study of Durvalumab (MEDI4736) Plus Tremelimumab for the Treatment of Patients With Progressive, Refractory Advanced Thyroid Carcinoma - The DUTHY Trial

Percentage of patients without progression of disease at month 6, according RECIST 1.1 criteria.

Percentage of patients alive at month 6 from first dose of treatment.

Response to treatment according to RECIST 1.1 criteria or iRECIST 1.1 criteria

Length of time between start of treatment and date of evidenced response and progression of disease according irRECIST or RECIST 1.1 criteria, or death

Length of time between date of evidenced response and progression of disease according irRECIST or RECIST 1.1 criteria, or death, or death

Number and type of adverse events reported throughout the study period

Length of time between start of treatment and death

MFAR

Grupo Espanol de Tumores Neuroendocrinos

Sirolimus

Anti-Bacterial Agents

Antibiotics, Antitubercular

Clotrimazole

Miconazole

Antifungal Agents

Sirolimus 4 mg, PO, days 1-28 as well as Cyclophosphamide 100 mg, PO, days 1-5 and 15-19

Cyclophosphamide 100 mg, PO, days 1-5 and 15-19

Cancer AnswerLine

Paul Swiecicki, M.D.

Francis Worden, M.D.

Paul Swieciki, M.D.

This study will be a non-randomized pilot trial using Cyclophosphamide and Sirolimus for the treatment of metastatic differentiated thyroid cancer. Patients will be treated with Sirolimus 4 mg, PO, days 1-28 as well as Cyclophosphamide 100 mg, PO, days 1-5 and 15-19. Cycle length will be 28 days. Patients will be monitored closely for toxicity and undergo imaging to evaluate efficacy once every 2 cycles.

Cyclophosphamide and Sirolimus for the Treatment of Metastatic, RAI-refractory, Differentiated Thyroid Cancer

An Open Label Phase II Trial Evaluating the Efficacy of Cyclophosphamide and Sirolimus for the Treatment of Metastatic, RAI-refractory, Differentiated Thyroid Cancer

The primary measure of efficacy will be the overall response rate (ORR) which is defined as those achieving either complete response (CR) or partial response (PR). Partial response is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions. Complete response is defined as Disappearance of all target lesions, determined by two separate observations conducted not less than 4 weeks apart (there can be no appearance of new lesions) and the disappearance of all non-target lesions and normalization of tumor marker level.

The number of patients that experience toxicity by type will be reported.

The median duration of time from start of treatment until death

The median duration of time from start of treatment until progression. Progression is defined as at least a 20% increase in the sum of the LD (longest diameter) of target lesions, taking as reference the smallest sum LD recorded since the treatment started, or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Phase 2, Open-label Study of AMG 706 to Treat Subjects With Locally Advanced or Metastatic Thyroid Cancer	NCT00121628	Thyroid Cancer	AMG 706	18 Years -	Amgen
Sutent Adjunctive Treatment of Differentiated Thyroid Cancer	NCT00668811	Papillary Thyro... Follicular Thyr... Differentiated ...	SU011248, Suten...	18 Years -	Medstar Health Research Institute
Administering Peripheral Blood Lymphocytes Transduced With a Murine T-Cell Receptor Recognizing Human Thyroglobulin to People With Thyroglobulin Expressing Thyroid Cancer	NCT02390739	Metastatic Thyr...	Aldesleukin Fludarabine Cyclophosphamid... Anti-Thyroglobu...	18 Years - 70 Years	National Institutes of Health Clinical Center (CC)
Restor. I-131 Upt. + Selpercatinib in RET F-P RAI-R TC	NCT05668962	Thyroid Cancer Thyroid Carcino... Metastatic Thyr... Follicular Thyr... Unresectable Th... Papillary Thyro...	Selpercatinib Sodium Iodine I... rhTSH	12 Years -	Massachusetts General Hospital
Administering Peripheral Blood Lymphocytes Transduced With a Murine T-Cell Receptor Recognizing Human Thyroglobulin to People With Thyroglobulin Expressing Thyroid Cancer	NCT02390739	Metastatic Thyr...	Aldesleukin Fludarabine Cyclophosphamid... Anti-Thyroglobu...	18 Years - 70 Years	National Institutes of Health Clinical Center (CC)
Durvalumab Plus Tremelimumab for the Treatment of Patients With Progressive, Refractory Advanced Thyroid Carcinoma -The DUTHY Trial	NCT03753919	Metastatic Thyr... Metastatic Thyr... Metastatic Thyr...	Durvalumab Tremelimumab	18 Years -	Grupo Espanol de Tumores Neuroendocrinos
Cyclophosphamide and Sirolimus for the Treatment of Metastatic, RAI-refractory, Differentiated Thyroid Cancer	NCT03099356	Metastatic Thyr...	Cyclophosphamid... Sirolimus	18 Years -	University of Michigan Rogel Cancer Center

Spots Global Cancer Trial Database for metastatic thyroid cancer