Atezolizumab With Chemotherapy in Treating Patients With Anaplastic or Poorly Differentiated Thyroid Cancer
Atezolizumab Combinations With Chemotherapy for Anaplastic and Poorly Differentiated Thyroid Carcinomas
2 other identifiers
interventional
50
1 country
1
Brief 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 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Jul 2017
Longer than P75 for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 6, 2017
CompletedFirst Posted
Study publicly available on registry
June 8, 2017
CompletedStudy Start
First participant enrolled
July 27, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 31, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
July 31, 2027
January 9, 2026
January 1, 2026
10 years
June 6, 2017
January 7, 2026
Conditions
Outcome Measures
Primary Outcomes (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.
5 years
Secondary Outcomes (6)
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)
5 years
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)
5 years
Efficacy determined per RECIST of taxanes + atezolizumab in cohort 4 with poorly differentiated thyroid cancer (PDTC)
5 years
Progression-free survival anaplastic thyroid carcinoma (ATC) and poorly differentiated thyroid cancer (PDTC)
5 years
Adverse events of targeted therapy + atezolizumab in cohorts 1-3 with anaplastic thyroid carcinoma (ATC) and poorly differentiated thyroid cancer (PDTC)
90 days after study drugs stopped
- +1 more secondary outcomes
Study Arms (4)
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.
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.
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.
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.
Interventions
Given IV
Given IV
Given PO
Given IV
Given IV
Given PO
Eligibility Criteria
You may qualify if:
- 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.
- 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.
- +11 more criteria
You may not qualify if:
- 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.
- 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).
- 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).
- History of serous retinopathy.
- History of retinal vein occlusion.
- History of ongoing serous retinopathy or RVO at baseline.
- +5 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- M.D. Anderson Cancer Centerlead
- National Cancer Institute (NCI)collaborator
Study Sites (1)
M D Anderson Cancer Center
Houston, Texas, 77030, United States
Related Publications (2)
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.
PMID: 39446377DERIVEDBaste 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.
PMID: 33720068DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Maria E Cabanillas
M.D. Anderson Cancer Center
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 6, 2017
First Posted
June 8, 2017
Study Start
July 27, 2017
Primary Completion (Estimated)
July 31, 2027
Study Completion (Estimated)
July 31, 2027
Last Updated
January 9, 2026
Record last verified: 2026-01