Symptoms and General Pathology

All Conditions

Neoplasms

Gland and Hormone Related Diseases

Rare Diseases

Recurrence

Carcinoma

Thyroid Neoplasms

Thyroid Cancer, Papillary

Carcinoma, Papillary

Thyroid Diseases

Carcinoma, Squamous Cell

Thyroid Carcinoma, Anaplastic

Carcinoma, Medullary

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Endocrine System Diseases

Endocrine Gland Neoplasms

Head and Neck Neoplasms

Carcinoma, Neuroendocrine

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Adenocarcinoma

Neoplasms, Nerve Tissue

Adenocarcinoma, Papillary

Papillary Thyroid Carcinoma

Anaplastic Thyroid Cancer

Thyroid Cancer, Medullary

Neuroendocrine Tumor

Neuroepithelioma

Patients receive selpercatinb PO BID on days 1-28. Treatment repeats every 28 days for up to 7 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care surgery.

Quality-of-Life Assessment

Questionnaire Administration

Selpercatinib

Therapeutic Conventional Surgery

Mark Zafereo

Francis Worden, MD

This phase II trial studies the effect of selpercatinib given before surgery in treating patients with thyroid cancer whose tumors have RET alterations (changes in the genetic material \[deoxyribonucleic acid (DNA)\]). Selpercatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving selpercatinib before surgery may help shrink the tumors and help control the disease.

PRIMARY OBJECTIVE:

I. To evaluate the efficacy of neoadjuvant selpercatinib in medullary thyroid cancer by objective response rate (ORR) per RECIST (standard Response Evaluation Criteria in Solid Tumors \[RECIST\]).

SECONDARY OBJECTIVES:

I. To evaluate the efficacy of neoadjuvant selpercatinib in medullary thyroid cancer by ORR per modified neck RECIST.

II. To evaluate the efficacy of neoadjuvant selpercatinib in medullary thyroid cancer per surgical margin status, which is categorized as R0, R1, and R2 surgical resection.

III. To evaluate the safety profile of neoadjuvant selpercatinib.

IV. To evaluate the efficacy of neoadjuvant selpercatinib on progression-free survival (PFS), including overall PFS and locoregional PFS.

V. To measure changes in expected and actual surgical morbidity/complexity as well as evaluate changes of R0/R1 resection rates in pre-specified extrathyroidal anatomic target interfaces before and after selpercatinib treatment.

EXPLORATORY OBJECTIVES:

I. In patients with differentiated thyroid cancer \[DTC\] and anaplastic thyroid cancer \[ATC\] only, to evaluate the efficacy of neoadjuvant selpercatinib by ORR per RECIST (standard RECIST and modified neck RECIST), surgical margin status (R0/R1 versus \[vs.\] R2), safety profile, surgical morbidity/complexity, PFS and overall survival (overall survival \[OS\], ATC only).

II. To define and measure changes of patient-reported outcomes and quality of life as measured by MD Anderson Symptom Inventory (MDASI) and European Quality of Life Five Dimension (EQ-5D) in patients with RET-altered thyroid cancer who receive selpercatinib treatment.

III. To explore translational endpoints in selpercatinib neoadjuvant therapy with biopsies/tissue collection before selpercatinib treatment and during surgery.

IV. To explore peripheral and tissue measures associated with selpercatinib mechanisms of resistance in patients who experience disease progression after selpercatinib treatment.

OUTLINE:

Patients receive selpercatinb orally (PO) twice daily (BID) on days 1-28. Treatment repeats every 28 days for up to 7 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care surgery.

After completion of study treatment, patients are followed up for disease progression status every 3-4 months for the first 2 years. ATC patients continue follow-up every 6 months for year 3 and 4, and once in year 5.

Selpercatinib Before Surgery for the Treatment of RET-Altered Thyroid Cancer

Neoadjuvant Treatment With Selpercatinib in RET-Altered Thyroid Cancers

Defined as the percentage of number of complete response or partial response in total number of patients treated. With ORR by Response Evaluation Criteria in Solid Tumors (RECIST), will report the percentages of patients that fall into each of the four categories: complete response, partial response, stable disease or progressive disease according to RECIST 1.1.

Assessed using modified neck RECIST, which applies the RECIST criteria only to lesions above the clavicles. Will report the percentages of patients that fall into each of the four categories: complete response, partial response, stable disease or progressive disease according to modified neck RECIST 1.1.

Defined by proportion of patients who undergo successful thyroidectomy with clear (R0) or microscopically positive (R1) surgical margins. Will evaluate R0/R1 resection rates in each of 4 pre-specified extrathyroidal anatomic target interfaces: 1) perithyroid muscles (e.g. strap, sternocleidomastoid, inferior constrictor muscles) 2) cartilage (larynx/trachea) 3) esophagus 4) recurrent laryngeal nerve.

Defined as the time from patient registration to disease progression or death from any cause. Structural progression is defined according to RECIST criteria based on histopathologic findings, and biochemical progression is defined as abnormal thyroglobulin (Tg) or rising Tg antibody levels for anaplastic thyroid cancer/differentiated thyroid cancer, and abnormal carcinoembryonic antigen/calcitonin for medullary thyroid cancer.

Defined as the time from patient registration to locoregional progression or death from any cause. Locoregional progression is defined as disease progression above the clavicles according to modified neck RECIST criteria.

Surgical morbidity/complexity score will be measured at enrollment, prior to surgery and at surgery. The Thyroid Neck Group Morbidity Complexity Scoring and MGH/MEE-MSK-MD Anderson (MMM) Surgical Morbidity Complexity Score are incorporated, specifying on scale with 5 levels of complexity and mobidity of the surgery \[mild (level 0), moderate (level 1), severe (level 2), very severe (level 3), and unresectable (level 4)\]. The surgical morbidity/complexity scores will be collected at enrollment, prior to surgery and at surgery; descriptive statistics such as means and standard deviations will be calculated for each time point.

Defined as the time from patient registration to death from any causes.

Assessed as defined by Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0.

Assessed by the European Quality of Life 5 Dimension Questionnaire (EQ-5D). The EQ-5D consists of health state description and evaluation. The health state description consists of five dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), with each dimension specifying five levels of severity \[best (1)-worst (5)\]. The health state evaluation is assessed using the visual analogue scale (\[worse (0)-best (100)\].

Measured by the M.D. Anderson Symptom Inventory for Head and Neck Cancer (MDASI-HN) instrument.

M.D. Anderson Cancer Center

Skin and Connective Tissue Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Musculoskeletal Diseases

Breast Neoplasms

Triple Negative Breast Neoplasms

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Sarcoma

Histiocytoma, Malignant Fibrous

Osteosarcoma

Carcinosarcoma

Mixed Tumor, Mullerian

Chondrosarcoma

Bone Neoplasms

Giant Cell Tumors

Giant Cell Tumor of Bone

Histiocytoma

Breast Diseases

Skin Diseases

Disease Attributes

Neoplasms, Connective and Soft Tissue

Neoplasms, Bone Tissue

Neoplasms, Connective Tissue

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Gonadal Disorders

Bone Diseases

Neoplasms, Fibrous Tissue

Ovarian Cancer

Ovarian Epithelial Cancer

Soft Tissue Sarcoma

Undifferentiated Pleomorphic Sarcoma

Malignant Mixed Mullerian Tumor

Ovarian Carcinosarcoma

All Drugs and Chemicals

Antineoplastic Agents

Antirheumatic Agents

Anti-Infective Agents

Analgesics

Amino Acids

Antibodies

Antibodies, Monoclonal

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Aldesleukin

Nivolumab

Ipilimumab

Immunoglobulins

Interleukin-2

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Analgesics, Non-Narcotic

Anti-HIV Agents

Anti-Retroviral Agents

Antiviral Agents

Serine

Ipilimumab will be administered as a single dose prior to tumor resection. Nivolumab will be administered once prior to tumor resection. Patients receive cyclophosphamide IV over 2 hours on days -7 and -6, fludarabine IV over 15-30 minutes daily on days -5 to -1, LN-145-S1 IV over 45 minutes on day 0 and aldesleukin IV over 30 minutes on days 1-4 for up to 6 doses. Within 12 weeks after receiving LN-145-S1, patients receive nivolumab IV over 30 minutes every 4 weeks in the absence of disease progression or unacceptable toxicity. The second dose will be administered prior to TIL administration and dosing will continue every 4 weeks and continued until unacceptable toxicity, progression, or start of another cancer therapy.

Patients receive cyclophosphamide IV over 2 hours on days -7 and -6, fludarabine IV over 15-30 minutes daily on days -5 to -1, autologous tumor infiltrating lymphocytes LN-145 IV over 45 minutes on day 0 and aldesleukin IV over 30 minutes on days 1-4 for up to 6 doses.

Autologous Tumor Infiltrating Lymphocytes LN-145

Autologous Tumor Infiltrating Lymphocytes LN-145-S1

Amir A Jazaeri

This phase II trial studies how well autologous tumor infiltrating lymphocytes LN-145 (LN-145) or LN-145-S1 works in treating patients with ovarian cancer, triple negative breast cancer (TNBC), anaplastic thyroid cancer, osteosarcoma, or other bone and soft tissue sarcomas that do not respond to treatment (refractory) or that has come back (relapsed).

LN-145 is made by collecting and growing specialized white blood cells (called T-cells) that are collected from the patient's tumor. LN-145-S1 is made using a modified process that chooses a specific portion of the T-cells. The T cells may specifically recognize, target, and kill the tumor cells.

PRIMARY OBJECTIVE:

I. To evaluate efficacy using objective response rate (ORR) using Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 in each cohort.

SECONDARY OBJECTIVES:

I. Determine the disease control rate (DCR) within and across cohorts. II. Determine the duration of response (DOR). III. Determine progression-free survival (PFS) and overall survival (OS). IV. Further characterize the safety profile of adoptive cell therapy with tumor infiltrating lymphocytes (TIL) across multiple tumor types.

EXPLORATORY OBJECTIVES:

I. Establish duration of tumor-infiltrating lymphocyte (TIL) persistence. II. Compare the molecular and immunological features of tumors before and after TIL therapy.

III. Prospectively evaluate the existing immunotherapy response criteria (immune-related \[ir\]RECIST) as the best response assessment tool for TIL therapy among a diverse group of solid tumors.

IV. To investigate TIL attributes (CD8 percentage \[%\], CD27 and CD28 expression) and correlation with response to therapy.

V. Assess tumor marker (CA-125) response in patients who produce this tumor marker.

VI. To assess Health-Related Quality of Life (HRQOL).

OUTLINE: Patients are assigned to 1 of 2 cohorts.

THYROID CANCER COHORT: Patients receive cyclophosphamide intravenously (IV) over 2 hours on days -7 and -6, fludarabine IV over 15-30 minutes daily on days -5 to -1, autologous tumor infiltrating lymphocytes LN-145 IV over 45 minutes on day 0 and aldesleukin IV over 30 minutes on days 1-4 for up to 6 doses.

ICI OVARIAN CANCER, OSTEOSARCOMA, Triple Negative Breast Cancer, or OTHER BONE AND SOFT TISSUE SARCOMAS COHORT: Within 2-4 weeks prior to surgery, patients receive a single dose of nivolumab IV over 30 minutes, followed by a single dose of ipilimumab IV over 30 minutes Patients receive cyclophosphamide IV over 2 hours on days -7 and -6, fludarabine IV over 15-30 minutes daily on days -5 to -1, LN-145-S1 IV over 45 minutes on day 0 and aldesleukin IV over 30 minutes on days 1-4 for up to 6 doses. Within 12 weeks after receiving LN-145-S1, patients receive nivolumab IV over 30 minutes every 4 weeks in the absence of disease progression or unacceptable toxicity.

For cohorts treated without immune checkpoint inhibitors, completion of treatment is defined as having received any volume of LN-145/LN-145-S1 infusion followed by at least 1 dose of adjuvant IL-2. For cohorts treated with TIL + ICI, completion of treatment will correspond to the last dose of nivolumab or IL2 (if the subject is deemed unsuitable to receive adjuvant nivolumab). Patients are followed up at 18 weeks, 6, 9, 12, 18 and 24 months, then every 3 months for at least 3 years.

LN-145 or LN-145-S1 in Treating Patients With Relapsed or Refractory Ovarian Cancer, Triple Negative Breast Cancer (TNBC), Anaplastic Thyroid Cancer, Osteosarcoma, or Other Bone and Soft Tissue Sarcomas

Clinical Study to Assess Efficacy and Safety of LN-145/LN-145-S1 (Autologous Centrally Manufactured Tumor Infiltrating Lymphocytes) Across Multiple Tumor Types

Determined by T-cell receptor (TCR) sequencing of infused T cells serially isolated following LN-145/LN-145-S1 infusion, or alternatively iRepertoire assessment of messenger ribonucleic acid for the TCRs.

Pearson correlation coefficient and linear regression, when appropriate, will be used to quantify the relationship between phenotypic attributes (CD8 percentage \[%\], CD27 and CD28 expression, etc.) and response to therapy.

Pearson correlation coefficient and linear regression, when appropriate, will be used to quantify the relationship between phenotypic attributes (CD8 %, CD27 and CD28 expression, etc.) and response to therapy.

Paired t-test will be used to examine the molecular and immunological features of tumors before and after TIL therapy.

Assessed per the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) questionnaire.

Assessed by Response Evaluation Criteria in Solid Tumors version 1.1. Estimation will use 80% confidence intervals by the Wilson score method.

Will be summarized using Kaplan-Meier estimates.

Iovance Biotherapeutics, Inc.

National Cancer Institute (NCI)

Lenvatinib

Pembrolizumab

Protein Kinase Inhibitors

Enzyme Inhibitors

Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 3 weeks for up to 35 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive lenvatinib PO daily on days 1-21. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

Maria E Cabanillas

Maria E. Cabanillas

This phase II trial studies how well lenvatinib and pembrolizumab work in treating patients with anaplastic thyroid cancer that is stage IVB and has spread to nearby tissue or lymph nodes (locally advanced) and cannot be removed by surgery (unresectable), or stage IVC that has spread to other places in the body (metastatic). Lenvatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Given lenvatinib and pembrolizumab may work better than giving either one alone in treating stage IVB or C anaplastic thyroid cancer.

PRIMARY OBJECTIVE:

I. Demonstrate the efficacy (overall survival \[OS\]) of lenvatinib plus pembrolizumab in treatment naive patients.

SECONDARY OBJECTIVES:

I. Determine the response rate and progression-free survival (PFS) in patients treated with lenvatinib plus pembrolizumab.

II. Establish safety for concurrent administration of lenvatinib plus pembrolizumab.

EXPLORATORY OBJECTIVE:

I. Translational endpoints: cell-free deoxyribonucleic acid (DNA) changes and immune biomarkers will be studied.

OUTLINE:

Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Treatment repeats every 3 weeks for up to 35 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive lenvatinib orally (PO) daily on days 1-21. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 2 years, and then annually thereafter.

Lenvatinib and Pembrolizumab for the Treatment of Stage IVB Locally Advanced and Unresectable or Stage IVC Metastatic Anaplastic Thyroid Cancer

Lenvatinib in Combination With Pembrolizumab for Stage IVB Locally Advanced and Unresectable or Stage IVC Metastatic Anaplastic Thyroid Cancer

Kaplan-Meier method will be used to estimate the overall survival distribution. 95% confidence intervals for median and probabilities will be computed.

Will be assessed by Response Evaluation Criteria in Solid Tumors.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Selpercatinib Before Surgery for the Treatment of RET-Altered Thyroid Cancer	NCT04759911	Malignant Thyro... Poorly Differen... Recurrent Thyro... Thyroid Gland A... Thyroid Gland M... Thyroid Gland P... Thyroid Gland S...	Quality-of-Life... Questionnaire A... Selpercatinib Therapeutic Con...	12 Years -	M.D. Anderson Cancer Center
LN-145 or LN-145-S1 in Treating Patients With Relapsed or Refractory Ovarian Cancer, Triple Negative Breast Cancer (TNBC), Anaplastic Thyroid Cancer, Osteosarcoma, or Other Bone and Soft Tissue Sarcomas	NCT03449108	Bone Sarcoma Dedifferentiate... Giant Cell Tumo... Malignancy in G... Malignant Solid... Ovarian Carcino... Platinum-Resist... Poorly Differen... Recurrent Osteo... Recurrent Ovari... Refractory Oste... Soft Tissue Sar... Thyroid Gland A... Thyroid Gland S... Undifferentiate... Triple Negative...	Aldesleukin Autologous Tumo... Autologous Tumo... Cyclophosphamid... Fludarabine Ipilimumab Nivolumab Quality-of-Life... Questionnaire A...	16 Years - 70 Years	M.D. Anderson Cancer Center
Lenvatinib and Pembrolizumab for the Treatment of Stage IVB Locally Advanced and Unresectable or Stage IVC Metastatic Anaplastic Thyroid Cancer	NCT04171622	Metastatic Thyr... Poorly Differen... Stage IVB Thyro... Stage IVC Thyro... Thyroid Gland S... Unresectable Th...	Lenvatinib Pembrolizumab	18 Years -	M.D. Anderson Cancer Center
Selpercatinib Before Surgery for the Treatment of RET-Altered Thyroid Cancer	NCT04759911	Malignant Thyro... Poorly Differen... Recurrent Thyro... Thyroid Gland A... Thyroid Gland M... Thyroid Gland P... Thyroid Gland S...	Quality-of-Life... Questionnaire A... Selpercatinib Therapeutic Con...	12 Years -	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for thyroid gland squamous cell carcinoma