Neoplasms

All Conditions

Gland and Hormone Related Diseases

Rare Diseases

Carcinoma

Carcinoma, Squamous Cell

Thyroid Neoplasms

Thyroid Diseases

Thyroid Carcinoma, Anaplastic

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Endocrine System Diseases

Endocrine Gland Neoplasms

Head and Neck Neoplasms

Anaplastic Thyroid Cancer

Antineoplastic Agents

All Drugs and Chemicals

Lenvatinib

Pembrolizumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

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.

National Cancer Institute (NCI)

M.D. Anderson Cancer Center

Paclitaxel

Albumin-Bound Paclitaxel

Bevacizumab

Atezolizumab

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Immunoglobulin G

Endothelial Growth Factors

Mitogens

Immunoglobulins, Intravenous

Vemurafenib

Tubulin Modulators

Antimitotic Agents

Angiogenesis Inhibitors

Growth Inhibitors

Immunologic Factors

Patients receive vemurafenib PO BID on days 1-21, cobimetinib PO QD on days 1-21, and atezolizumab IV over 30-60 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression and unacceptable toxicity.

Patients receive cobimetinib PO QD on days 1-21 and atezolizumab IV over 30-60 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression and unacceptable toxicity.

Patients receive atezolizumab IV over 30-60 minutes and bevacizumab IV over 60-90 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression and unacceptable toxicity.

Patients receive nab-paclitaxel IV over 30 minutes on days 1, 8, and 15 and atezolizumab IV on day 1 over 30-60 minutes. Patients may receive paclitaxel IV over 30 minutes on day 1 as a substitute for nab-paclitaxel. Cycles repeat every 21 days in the absence of disease progression and unacceptable toxicity.

Cobimetinib

Nab-paclitaxel

This phase II trial studies how well atezolizumab in combination with chemotherapy works in treating patients with anaplastic or poorly differentiated thyroid cancer. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Vemurafenib and cobimetinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of cancer cells to grow and spread. Drugs such as nab-paclitaxel and paclitaxel work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. This trial is being done to see if atezolizumab in combination with chemotherapy works better in treating patients with anaplastic or poorly differentiated thyroid cancer compared to standard treatments.

PRIMARY OBJECTIVE:

I. To determine if targeted therapy + atezolizumab (cohorts 1-3) will lead to improved overall survival (OS) in patients with anaplastic thyroid carcinoma (ATC).

SECONDARY OBJECTIVES:

I. To evaluate the safety and efficacy (Response Evaluation Criteria in Solid Tumors \[RECIST\] response rate, progression-free survival \[PFS\]) of targeted therapy + atezolizumab (cohorts 1-3) in ATC and poorly differentiated thyroid cancer (PDTC).

II. To determine the OS in patients with PDTC treated with targeted therapy + atezolizumab (cohorts 1-3).

III. To determine the efficacy (RECIST/immune-related Response Criteria \[irRC\] response rate, progression-free survival \[PFS\]) and OS of ATC and PDTC patients treated with taxanes + atezolizumab (cohort 4).

EXPLORATORY OBJECTIVES:

I. To evaluate changes in the tumor-associated and systemic immune system biomarkers in ATC and PDTC patients treated with immunotherapy.

II. To report radioactive iodine (RAI) uptake in patients who have a diagnostic whole body scan and therapeutic I-131 in cohort 2.

OUTLINE: Patients are assigned to 1 of 4 cohorts.

COHORT I (BRAF MUTATION): Patients receive vemurafenib orally (PO) twice daily (BID) on days 1-21, cobimetinib PO once daily (QD) on days 1-21, and atezolizumab intravenously (IV) over 30-60 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression and unacceptable toxicity.

COHORT II (RAS, NF1, OR NF2 MUTATION including patients with MAPK activating mutations at or above MEK): Patients receive cobimetinib PO QD on days 1-21 and atezolizumab IV over 30-60 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression and unacceptable toxicity.

COHORT III (NON-BRAF/NON-RAS MUTATION): Patients receive atezolizumab IV over 30-60 minutes and bevacizumab IV over 60-90 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression and unacceptable toxicity.

COHORT IV: Patients receive nab-paclitaxel IV over 30 minutes on days 1, 8, and 15 and atezolizumab IV over 30-60 minutes on day 1. Patients may receive paclitaxel IV over 30 minutes on day 1 as a substitute for nab-paclitaxel. Cycles repeat every 21 days in the absence of disease progression and unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for years 1-2, every 6 months for years 3-4, then yearly thereafter.

Atezolizumab With Chemotherapy in Treating Patients With Anaplastic or Poorly Differentiated Thyroid Cancer

Atezolizumab Combinations With Chemotherapy for Anaplastic and Poorly Differentiated Thyroid Carcinomas

Overall survival is defined as the time from start date of cohort specific treatment to death from any cause will be estimated using the Kaplan-Meier method.

Progression-free survival defined as the time from start date of cohort specific treatment to progression or death (whichever occurs first) will be estimated using the Kaplan-Meier method.

Adverse events recorded per The Common Terminology Criteria for Adverse Events (CTCAE).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
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
Atezolizumab With Chemotherapy in Treating Patients With Anaplastic or Poorly Differentiated Thyroid Cancer	NCT03181100	Metastatic Thyr... Poorly Differen... Stage IVA Thyro... Stage IVB Thyro... Stage IVC Thyro... Thyroid Gland A... Unresectable Th...	Atezolizumab Bevacizumab Cobimetinib Nab-paclitaxel Paclitaxel Vemurafenib	18 Years -	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for stage ivc thyroid gland anaplastic carcinoma ajcc v8