PD-1 Inhibitor and Anlotinib Combined With Multimodal Radiotherapy in Recurrent or Metastatic Anaplastic Thyroid Cancer

NCT05659186 | Unknown Phase 2

• 1 other identifier: ChiCTR2100054455
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of PD-1 inhibitor and anlotinib combined with multimodal radiotherapy for the second-line treatment of recurrent or metastatic anaplastic thyroid cancer.

Conditions

Thyroid Cancer

Keywords

Thyroid Cancer; Immunotherapy; Radiotherapy; Anlotinib

Outcome Measures

Primary Outcomes (1)

• Objective response rate

  ORR is defined as the percentage of patients who achieve a response, which can either be complete response (complete disappearance of lesions) or partial response (reduction in the sum of maximal tumor diameters by at least 30% or more)

  Up to 60 months

Secondary Outcomes (3)

• Progress-Free Survival

  Up to 60 months

• Overall Survival

  Up to 60 months

• Adverse events

  Up to 60 months

Study Arms (1)

Treatment Cohort

EXPERIMENTAL

Tislelizumab administration on day 1, and Anlotinib continuous administration from days 1 to 14， every three weeks Radiotherapy

Drug: Tislelizumab; Drug: Anlotinib; Radiation: Radiotherapy

Interventions

Tislelizumab DRUG

200mg IV Q3W

Also known as: BGB-A317

Treatment Cohort

Anlotinib DRUG

12mg PO QD

Also known as: AL3818

Treatment Cohort

Radiotherapy RADIATION

Multimodal Radiotherapy

Treatment Cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 years or above.
• Patients with pathologically confirmed Undifferentiated thyroid carcinoma and meet the following conditions:
• Were diagnosed with distant metastasis;
• Were intolerant to or failed first-line treatment.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
• Expected life is greater than or equal to 12 weeks.
• There is at least one measurable lesion according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
• Adequate organ and bone marrow function:
• Absolute neutrophil count ≥ 1.5 × 10\^9/L, hemoglobin ≥ 80 g/L, platelets ≥ 80 × 10\^9/L;
• ALT, AST and ALP \< 2.5× upper limit of normal (ULN), total bilirubin ≤ 2×ULN; albumin≥ 2.8 g/dL；
• Creatinine clearance ≥ 60 ml/min;
• INR≤ 1.5, APTT≤ 1.5×ULN.
• Written informed consent.

You may not qualify if:

• Existing tumor-related hemorrhage。
• History of other malignancies (except for the history of malignant tumors that have been cured and have not recurred within 5 years, such as skin basal cell carcinoma, skin squamous cell carcinoma, superficial bladder cancer, in situ cervical cancer, and gastrointestinal mucosal cancer, etc.）
• Have an active autoimmune disease requiring systemic treatment or a documented history of clinically severe autoimmune disease.
• Any history of allergic disease, severe hypersensitivity reaction to drugs, or allergy to the study drug components.
• Any prior therapy with:
• Antitumor vaccine;
• Any active vaccine against infectious disease within 4 weeks prior to the first dose or planned during the study period;
• Major surgery or serious trauma within 4 weeks before the first dose;
• With serious medical diseases, such as grade II and above cardiac dysfunction (NYHA criteria), ischemic heart disease, supraventricular or ventricular arrhythmia, poorly controlled diabetes mellitus, poorly controlled hypertension, echocardiographic ejection fraction \< 50%, etc.
• With interstitial pneumonitis, non-infectious pneumonitis, active pulmonary tuberculosis, or a history of pulmonary tuberculosis infection that was not controlled by treatment.
• With hyperthyroidism, or organic thyroid disease.
• With active infection, or unexplained fever during the screening period or 48 hours before the first dose.
• With active hepatitis B or C, or known history of positive HIV test, or acquired immunodeficiency syndrome.
• History of a clear neurological or psychiatric disorder.
• History of drug abuse or alcohol abuse.

Sponsors & Collaborators

• West China Hospital: lead

Study Sites (1)

Xingchen Peng

Chengdu, Sichuan, 610041, China

RECRUITING

Related Publications (15)

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  PMID: 31632557 BACKGROUND

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• Haddad RI, Nasr C, Bischoff L, Busaidy NL, Byrd D, Callender G, Dickson P, Duh QY, Ehya H, Goldner W, Haymart M, Hoh C, Hunt JP, Iagaru A, Kandeel F, Kopp P, Lamonica DM, McIver B, Raeburn CD, Ridge JA, Ringel MD, Scheri RP, Shah JP, Sippel R, Smallridge RC, Sturgeon C, Wang TN, Wirth LJ, Wong RJ, Johnson-Chilla A, Hoffmann KG, Gurski LA. NCCN Guidelines Insights: Thyroid Carcinoma, Version 2.2018. J Natl Compr Canc Netw. 2018 Dec;16(12):1429-1440. doi: 10.6004/jnccn.2018.0089.

  PMID: 30545990 BACKGROUND

• Sun C, Li Q, Hu Z, He J, Li C, Li G, Tao X, Yang A. Treatment and prognosis of anaplastic thyroid carcinoma: experience from a single institution in China. PLoS One. 2013 Nov 5;8(11):e80011. doi: 10.1371/journal.pone.0080011. eCollection 2013.

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• Perrier ND, Brierley JD, Tuttle RM. Differentiated and anaplastic thyroid carcinoma: Major changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin. 2018 Jan;68(1):55-63. doi: 10.3322/caac.21439. Epub 2017 Nov 1.

  PMID: 29092098 BACKGROUND

• Subbiah V, Kreitman RJ, Wainberg ZA, Cho JY, Schellens JHM, Soria JC, Wen PY, Zielinski C, Cabanillas ME, Urbanowitz G, Mookerjee B, Wang D, Rangwala F, Keam B. Dabrafenib and Trametinib Treatment in Patients With Locally Advanced or Metastatic BRAF V600-Mutant Anaplastic Thyroid Cancer. J Clin Oncol. 2018 Jan 1;36(1):7-13. doi: 10.1200/JCO.2017.73.6785. Epub 2017 Oct 26.

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• Chintakuntlawar AV, Yin J, Foote RL, Kasperbauer JL, Rivera M, Asmus E, Garces NI, Janus JR, Liu M, Ma DJ, Moore EJ, Morris JC 3rd, Neben-Wittich M, Price DL, Price KA, Ryder M, Van Abel KM, Hilger C, Samb E, Bible KC. A Phase 2 Study of Pembrolizumab Combined with Chemoradiotherapy as Initial Treatment for Anaplastic Thyroid Cancer. Thyroid. 2019 Nov;29(11):1615-1622. doi: 10.1089/thy.2019.0086.

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• Pezzi TA, Mohamed ASR, Sheu T, Blanchard P, Sandulache VC, Lai SY, Cabanillas ME, Williams MD, Pezzi CM, Lu C, Garden AS, Morrison WH, Rosenthal DI, Fuller CD, Gunn GB. Radiation therapy dose is associated with improved survival for unresected anaplastic thyroid carcinoma: Outcomes from the National Cancer Data Base. Cancer. 2017 May 1;123(9):1653-1661. doi: 10.1002/cncr.30493. Epub 2016 Dec 27.

  PMID: 28026871 BACKGROUND

• Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Carvajal RD, Sosman JA, Atkins MB, Leming PD, Spigel DR, Antonia SJ, Horn L, Drake CG, Pardoll DM, Chen L, Sharfman WH, Anders RA, Taube JM, McMiller TL, Xu H, Korman AJ, Jure-Kunkel M, Agrawal S, McDonald D, Kollia GD, Gupta A, Wigginton JM, Sznol M. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012 Jun 28;366(26):2443-54. doi: 10.1056/NEJMoa1200690. Epub 2012 Jun 2.

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• Chintakuntlawar AV, Rumilla KM, Smith CY, Jenkins SM, Foote RL, Kasperbauer JL, Morris JC, Ryder M, Alsidawi S, Hilger C, Bible KC. Expression of PD-1 and PD-L1 in Anaplastic Thyroid Cancer Patients Treated With Multimodal Therapy: Results From a Retrospective Study. J Clin Endocrinol Metab. 2017 Jun 1;102(6):1943-1950. doi: 10.1210/jc.2016-3756.

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• Lorusso L, Pieruzzi L, Biagini A, Sabini E, Valerio L, Giani C, Passannanti P, Pontillo-Contillo B, Battaglia V, Mazzeo S, Molinaro E, Elisei R. Lenvatinib and other tyrosine kinase inhibitors for the treatment of radioiodine refractory, advanced, and progressive thyroid cancer. Onco Targets Ther. 2016 Oct 20;9:6467-6477. doi: 10.2147/OTT.S84625. eCollection 2016.

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• Sun Y, Niu W, Du F, Du C, Li S, Wang J, Li L, Wang F, Hao Y, Li C, Chi Y. Safety, pharmacokinetics, and antitumor properties of anlotinib, an oral multi-target tyrosine kinase inhibitor, in patients with advanced refractory solid tumors. J Hematol Oncol. 2016 Oct 4;9(1):105. doi: 10.1186/s13045-016-0332-8.

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• Ruan X, Shi X, Dong Q, Yu Y, Hou X, Song X, Wei X, Chen L, Gao M. Antitumor effects of anlotinib in thyroid cancer. Endocr Relat Cancer. 2019 Jan 1;26(1):153-164. doi: 10.1530/ERC-17-0558.

  PMID: 30139768 BACKGROUND

• Gunda V, Gigliotti B, Ashry T, Ndishabandi D, McCarthy M, Zhou Z, Amin S, Lee KE, Stork T, Wirth L, Freeman GJ, Alessandrini A, Parangi S. Anti-PD-1/PD-L1 therapy augments lenvatinib's efficacy by favorably altering the immune microenvironment of murine anaplastic thyroid cancer. Int J Cancer. 2019 May 1;144(9):2266-2278. doi: 10.1002/ijc.32041. Epub 2019 Jan 24.

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  PMID: 25481261 BACKGROUND

MeSH Terms

Conditions

Thyroid Neoplasms

Interventions

tislelizumab; anlotinib; Radiotherapy

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Endocrine System Diseases; Thyroid Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Xingchen Peng, Professor

  West China Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xingchen Peng, Professor

CONTACT

+86 18980606753; pxx2014@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 8, 2022
• First Posted: December 21, 2022
• Study Start: December 30, 2022
• Primary Completion: December 30, 2024
• Study Completion: December 30, 2025
• Last Updated: December 21, 2022

Record last verified: 2022-12

Locations

CN (1)