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AzTrials

Metastatic Thyroid Gland CarcinomaPhase 2NCT03181100

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

A Phase 2 study testing Atezolizumab, Bevacizumab and Cobimetinib in people with Metastatic Thyroid Gland Carcinoma and Poorly Differentiated Thyroid Gland Carcinoma, run by M.D. Anderson Cancer Center at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Atezolizumab, Bevacizumab and Cobimetinib
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
1 siteUnited States
Study dates
27 Jul 2017to 31 Jul 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

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

  • Histologically confirmed anaplastic thyroid or poorly differentiated thyroid carcinomas.
  • Patients deemed to have unresectable locoregional disease or metastatic disease. Patients who are unwilling to undergo surgery or external beam radiation are also eligible.
  • Patients with poorly differentiated thyroid cancer must have at least one target lesion by RECIST version 1.1. This is not a requirement for ATC patients.
  • Total bilirubin =< 1.5 x upper limit of normal (ULN). Total bilirubin: 3 x ULN for patients with Gilbert's syndrome.
  • Aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT) / alanine aminotransferase (ALT) serum glutamate pyruvate transaminase (SGPT) =< 2.5 x ULN, (5 x ULN for patients with concurrent liver metastases).
  • Serum creatinine =< within 1.5 x ULN.
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  • Absolute neutrophil count (ANC) >= 1.0 x 10^9 /L.
  • Platelets (PLT) >= 100 x 10^9 /L.
  • For patients receiving therapeutic anticoagulation: stable anticoagulant regimen and stable international normalized ratio (INR) during the 28 days immediately preceding initiation of study treatment.
  • Subjects must be willing to undergo tumor biopsy prior to and after treatment with atezolizumab, unless in the opinion of the treating physician, a biopsy is not feasible or safe.
  • Eastern Cooperative Oncology Group (ECOG) performance score (PS) =< 2.
  • Age and reproductive status:
  • Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within 14 days prior to the start of study drug and must use effective contraceptives throughout the duration of the study. Males who are sexually active with WOCBP must agree to use effective contraception throughout the duration of the study. Azoospermic males and WOCBP who are continuously not heterosexually active are exempt from contraceptive requirements.
  • A Women of childbearing potential (WOCBP) is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) and is not postmenopausal. Menopause is defined as 12 months of amenorrhea in a woman over age 45 years in the absence of other biological or physiological causes.
  • Ability to provide informed consent.
  • ADDITIONAL INCLUSION CRITERIA FOR BRAF MUTATION (COHORT 1): Patients with a BRAFV600E mutation being considered for the triplet combination (vemurafenib + cobimetinib + atezolizumab) must meet the following end organ function criteria:
  • COHORT 1: ANC >= 1.5 × 10^9 /L without granulocyte colony-stimulating factor support.
  • COHORT 1: White blood cell (WBC) count >= 2.5 x 10^9 /L.
  • COHORT 1: Lymphocyte count >= 0.5 x 10^9/L.
  • COHORT 1: Platelet count >= 100 × 10^9 /L without transfusion.
  • COHORT 1: Hemoglobin >= 9.0 g/L without transfusion.
  • COHORT 1: Serum albumin > =2.5 g/L
  • COHORT 1: Total bilirubin =< 1.5 x ULN
  • COHORT 1: AST and ALT =< 2.0 x ULN
  • COHORT 1: Alkaline phosphatase (ALP) =< 2.5 x ULN or, for patients with documented liver or bone metastases, ALP =< 5 x ULN
  • COHORT 1: Serum creatinine =< 1.5 x ULN or creatinine clearance (CrCl) >= 40 mL/min on the basis of measured CrCl from a 24-hour urine collection or Cockcroft-Gault glomerular filtration rate estimation.
  • COHORT 1: Patients with BRAF mutation may be screened for eligibility in cohorts 2, 3, or 4 (in this order of preference) if they do not meet the entry criteria for cohort 1.

Who cannot join

  • Subjects with an active, known or suspected autoimmune disease. Subjects with type I diabetes mellitus on stable insulin regimen, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
  • For patients not receiving therapeutic anticoagulation: INR or partial thromboplastin time (aPTT) > 1.5 x ULN within 28 days prior to initiation of study treatment.
  • Prior treatment with anti-PD-1, or anti-PD-L1 therapeutic antibody or pathway targeting agents. Patients who have received prior treatment with anti-CTLA-4 may be enrolled, provided the following requirements are met: Minimum of 12 weeks from the first dose of anti-CTLA-4 and > 6 weeks from the last dose, and no history of severe immune-related adverse effects from anti-CTLA 4 (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] grade 3 and 4).
  • Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease.
  • History of human immunodeficiency virus (HIV) infection or active hepatitis B (chronic or acute) or hepatitis C infection Patients with past or resolved hepatitis B infection (defined as having a negative hepatitis B surface antigen [HBsAg] test and a positive anti-HBc [antibody to hepatitis B core antigen] antibody test) are eligible. However, patients with past or resolved hepatitis B virus (HBV) should be monitored for reactivation by a specialist. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV ribonucleic acid (RNA).
  • Pregnant or lactating women. All pre-menopausal women being screened must have a negative serum pregnancy test within 14 days prior to commencement of dosing. Women of non-childbearing potential may be included if they are either surgically sterile or have been postmenopausal for >= 1 year. Fertile men and women must use an effective method of contraception during treatment and for at least 6 months after completion of treatment as directed by their physician.
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  • Untreated brain metastases.
  • Chemotherapy within 21 days of enrollment with the exception of paclitaxel or nab-paclitaxel (Abraxane). Patients who have received one course of these agents prior to study entry are eligible. (One course of weekly paclitaxel or nab-paclitaxel is 3 doses. One course of every 3 week dosing of paclitaxel or nab-paclitaxel is 1 dose). Patients who have received prior radiosensitizing chemotherapy are eligible.
  • The use of corticosteroids is not allowed for 10 days prior to initiation of atezolizumab except patients who are taking steroids for physiological replacement. Inhaled or topical steroids, and adrenal replacement steroid doses are permitted in the absence of active autoimmune disease. This does not apply to patients receiving steroids as pre-medications for paclitaxel administration.
  • Grade >= 2 uncontrolled hypertension (patients with a history of hypertension controlled with anti-hypertensive medication to Grade =< 1 are eligible).
  • ADDITIONAL EXCLUSION CRITERIA FOR non-BRAF/non-RAS MUTATION (COHORT 3):
  • Patients with clinically significant hemoptysis or tumor bleeding within two weeks prior to first dose of targeted therapy.
  • Patients with suspected tracheal or esophageal invasion are excluded from cohort 3 due to the high risk of trachealesophageal fistula. Patients excluded from cohort 3 may be enrolled on taxane + atezolizumab cohort (cohort 4).
  • ADDITIONAL EXCLUSION CRITERIA FOR COHORTS 1 and 2: Ocular Exclusion Criteria for vemurafenib and cobimetinib containing cohorts-cohorts 1 and 2. (However, these patients may be assigned other cohorts if they do not meet the ocular exclusion criteria): History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment, central serous chorioretinopathy, retinal vein occlusion (RVO), or neovascular macular degeneration Patients will be excluded from participation in cohorts 1 and 2 if they currently are known to have any of the following risk factors for RVO unless a retinal specialist has determined that the risk of retinal detachment is low:
  • History of serous retinopathy.
  • History of retinal vein occlusion.
  • History of ongoing serous retinopathy or RVO at baseline.
  • ADDITIONAL EXCLUSION CRITERIA FOR PATIENTS IN COHORT 1 (vemurafenib+cobimetinib+atezolizumab): History of clinically significant cardiac dysfunction, including the following:
  • Mean (average of triplicate measurements) QTc interval corrected using Fridericia's method >= 480 ms at screening, or uncorrectable abnormalities in serum electrolytes (sodium, potassium, calcium, magnesium, and phosphorus).
  • ADDITIONAL EXCLUSION CRITERIA FOR PATIENTS IN COHORTS 1 and 2 (cobimetinib-containing cohorts):
  • Unstable angina, or new-onset angina within 3 months prior to initiation of study treatment.
  • Symptomatic congestive heart failure, defined as New York Heart Association Class II or higher.
  • Myocardial infarction within 3 months prior to initiation of study treatment.
  • Left ventricular ejection fraction below the institutional lower limit of normal or below 50%, whichever is lower.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: Atezolizumab Combinations With Chemotherapy for Anaplastic and Poorly Differentiated Thyroid Carcinomas

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. 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:

  1. 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:

  1. 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.

Medical subject headings
Thyroid Neoplasms, Thyroid Carcinoma, Anaplastic

What participants receive

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

  • AtezolizumabDrug

    Also called MPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A

    Given IV

  • BevacizumabBiological

    Also called Anti-VEGF, Anti-VEGF Humanized Monoclonal Antibody, Anti-VEGF rhuMAb, Avastin

    Given IV

  • CobimetinibDrug

    Also called Cotellic, GDC-0973, MEK Inhibitor GDC-0973, XL518

    Given PO

  • Nab-paclitaxelDrug

    Also called ABI 007, ABI-007, Abraxane, Albumin-bound Paclitaxel

    Given IV

  • PaclitaxelDrug

    Also called Anzatax, Asotax, Bristaxol, Praxel

    Given IV

  • VemurafenibDrug

    Also called BRAF (V600E) kinase inhibitor RO5185426, BRAF(V600E) Kinase Inhibitor RO5185426, PLX-4032, PLX4032

    Given PO

Study groups in NCT03181100
Study groupRoleWhat they receive
Cohort I (vemurafenib, cobimetinib, atezolizumab)ExperimentalPatients 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.
Receives: Drug: Atezolizumab; Drug: Cobimetinib; Drug: Vemurafenib
Cohort II (atezolizumab, cobimetinib)ExperimentalPatients 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.
Receives: Drug: Atezolizumab; Drug: Cobimetinib
Cohort III (atezolizumab, bevacizumab)ExperimentalPatients 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.
Receives: Drug: Atezolizumab; Biological: Bevacizumab
Cohort IV (nab-paclitaxel, atezolizumab, paclitaxel,)ExperimentalPatients 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.
Receives: Drug: Atezolizumab; Drug: Nab-paclitaxel; Drug: Paclitaxel

What is being measured

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

  1. Overall survival (OS) with targeted therapy + atezolizumab in cohorts 1 and 3 with anaplastic thyroid carcinoma (ATC)

    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.

    Measured: 5 years

Secondary outcomes (6)

  1. Efficacy determined per Response Evaluation Criteria for Solid Tumors (RECIST) of targeted therapy + atezolizumab in Cohorts 1-3 with anaplastic thyroid carcinoma (ATC) and poorly differentiated thyroid cancer (PDTC)

    Measured: 5 years

  2. Efficacy determined per immune related (ir)RECIST of targeted therapy + atezolizumab in Cohorts 1-3 with anaplastic thyroid carcinoma (ATC) and poorly differentiated thyroid cancer (PDTC)

    Measured: 5 years

  3. Efficacy determined per RECIST of taxanes + atezolizumab in cohort 4 with poorly differentiated thyroid cancer (PDTC)

    Measured: 5 years

  4. Progression-free survival anaplastic thyroid carcinoma (ATC) and poorly differentiated thyroid cancer (PDTC)

    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.

    Measured: 5 years

  5. Adverse events of targeted therapy + atezolizumab in cohorts 1-3 with anaplastic thyroid carcinoma (ATC) and poorly differentiated thyroid cancer (PDTC)

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

    Measured: 90 days after study drugs stopped

  6. Adverse events of taxanes + atezolizumab in cohort 4 with poorly differentiated thyroid cancer (PDTC)

    Adverse events recorded per CTCAE.

    Measured: 90 days after study drugs stopped

Timeline

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

  1. First posted8 Jun 2017
  2. Study start27 Jul 2017
  3. Primary completion31 Jul 2027 (estimated)
  4. Study completion31 Jul 2027 (estimated)

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
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
50 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03181100
Sponsor's protocol ID
2016-0916
Other IDs
NCI-2019-02581, 2016-0916
Status last verified
Jul 2026
First submitted
6 Jun 2017
Last updated
24 Jul 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Cabanillas ME, Dadu R, Ferrarotto R, Gule-Monroe M, Liu S, Fellman B, Williams MD, Zafereo M, Wang JR, Lu C, Ning M, McKinley BA, Woodman SE, Duose D, Gunn GB, Busaidy NL; Rare Tumor Initiative Team. Anti-Programmed Death Ligand 1 Plus Targeted Therapy in Anaplastic Thyroid Carcinoma: A Nonrandomized Clinical Trial. JAMA Oncol. 2024 Dec 1;10(12):1672-1680. doi: 10.1001/jamaoncol.2024.4729.

    PubMed 39446377

  • Baste N, Mora M, Grau JJ. Emerging systemic antitarget treatment for differentiated thyroid carcinoma. Curr Opin Oncol. 2021 May 1;33(3):184-195. doi: 10.1097/CCO.0000000000000727.

    PubMed 33720068

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Atezolizumab, Bevacizumab and Cobimetinib in people with Metastatic Thyroid Gland Carcinoma and Poorly Differentiated Thyroid Gland Carcinoma, run by M.D. Anderson Cancer Center 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 27 inclusion and 24 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: under way, not looking for participants, as of the sponsor's last update on 24 Jul 2026. 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?

This study is still under way. Results are not available in the source record yet.

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?

Overall survival (OS) with targeted therapy + atezolizumab in cohorts 1 and 3 with anaplastic thyroid carcinoma (ATC) (time frame: 5 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03181100, which also lists 2 linked publications.

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 24 Jul 2026.

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