Anlotinib, Penpulimab and Capecitabine in Recurrent/Metastatic Nasopharyngeal Carcinoma

NCT05807880 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: ALTER-HN005
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 1

Brief Summary

First-diagnosed metastasis or recurrence/metastasis NPC Patients will be treated with anlotinib, penpulimab and capecitabine.

Conditions

Nasopharyngeal Neoplasms

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS）

  Progression-free survival is measured according to the RECIST 1.1.

  3-year

Secondary Outcomes (6)

• Objective remission rate (ORR)

  Median value

• Progression-free survival (PFS)

  3-year

• Overall survival (OS)

  3-year

• Quality of Life (QoL)

  3-year

• Quality of Life (QoL)

  3-year

Study Arms (1)

Intervention arm

EXPERIMENTAL

First, patients will receive the combination treatment of anlotinib, penpulimab and capecitabine every three weeks for 4-6 cycles. For each cycle, patients receive anlotinib 10mg, po, qd from day 1 to day 14, penpulimab 200mg, iv in day 1, and capecitabine 650mg/m2, po, bid from day 1 to day 21. Then a maintenance treatment will be run with "penpulimab and capecitabine"(the dose and the medication method remain the same) for every 3 weeks until PD or intolerance to drug toxicity. Note: After using the penpulimab for 2 years, it is dependent on the researcher's judgement of the benefit evaluation whether to continue using it.

Drug: The combination treatment of anlotinib, penpulimab and capecitabine.

Interventions

The combination treatment of anlotinib, penpulimab and capecitabine. DRUG

Patients will receive the combination treatment of anlotinib, penpulimab and capecitabine every three weeks until PD or intolerance to drug toxicity. For each cycle, patients receive anlotinib 10mg, po, qd from day 1 to day 14, penpulimab 200mg, iv in day 1, and capecitabine 650mg/m2, po, bid.

Intervention arm

Eligibility Criteria

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

You may qualify if:

• Between 18 to 65 years old.
• ECOG PS score 0-1 point.
• Having at least one measurable lesion confirmed by the RECIST 1.1.
• Locoregionally advanced nasopharyngeal carcinoma patients, who have never received systematic treatment for recurrent or metastatic lesion, was found with recurrence or metastasis in at least 6 months after completing chemotherapy and radiotherapy of the primary lesion. Never receive immune-checkpoint inhibitors (anti-PD-1 monoclonal antibody or anti PD-L1 monoclonal antibody, etc) treatment. In radical treatment phase of locoregional nasopharyngeal carcinoma, patients received no more than 1 type of immune-checkpoint inhibitor (limited to CTLA-4/PD-1/PD-L1 monoclonal antibody, not including bi-specific antibody or penpulimab) can be included:
• i: If the patient received immune-checkpoint inhibitors (with or without other drugs) during induction therapy, the optimal treatment effect should be PR or better than PR.
• ii: If the patient received immune-checkpoint inhibitors (with or without other drugs) during radiotherapy, there should be no progression during treatment and within 6 months after treatment.
• According to the researchers' judgement, the target lesion cannot benefit from radiotherapy.
• The major organs' function is normal, and meets following criteria 7 days before intervention:
• Blood routine should meet (No blood transfusion or blood product within the past 14 days, and no correction was used with G-CSF or other hematopoietic stimulating factors.):
• Hemoglobin (HB) ≥ 90g/L;
• White blood cell (WBC) ≥ 4\*109/L;
• Blood platelet (PLT): 100\_109/L;
• Biochemistry examination should meet:
• Total bilirubin (TBIL) ≤ 1.5\*upper limit of normal (ULN);
• Alanine transaminase (ALT) and aspartate transaminase (AST) ≤ 2.5\*ULN;

You may not qualify if:

• Patients who meet any of the following criteria should be excluded:
• Disease progression within 6 months after the standard therapy of locoregional advanced nasopharyngeal carcinoma;
• Patients who cannot accept MR examination for metal implant or claustrophobia;
• Patients who need systemically using glucocorticoid (\> 10mg prednisone per day) or other immunosuppressive drugs treatment in 14 days before intervention or during intervention. If the patient doesn't have active autoimmune disease, it is allowed to use invasive or topical corticosteroid and adrenocorticotropic hormone (ACTH) that is equivalent to \> 10mg/day prednisone, and ACTH replacement therapy that is equivalent to ≤ 10mg/ day prednisone therapeutic dose.
• Patient who has recurrent lesion that is suitable for operation or second-course radiotherapy or, based on the judgement of the doctor in charge, can profit from the radiotherapy for the target lesion.
• Patient has active immune or autoimmune disease history, or known allograft history, or allogeneic hematopoietic stem cell transplantation history, excluding type 1 diabetes, hypothyroidism that need hormone replacement therapy and dermatologic diseases that don't need systemic treatment (e.g. leucoderma, psoriasis and alopecia.).
• Patient who had active tuberculosis history in the past 1 year, with or without treatment. Apart from those with a proven history of regular antituberculosis therapy, patients with \> 1-year active pulmonary tuberculosis history should be excluded.
• Patients with hypertension history, and their blood pressure was not well-controlled (systolic pressure ≥ 150 mmHg or diastolic pressure ≥ 90 mmHg) after 1 kind of drug treatment.
• Having significant clinical ischemia symptom or specific ischemia tendency, especially to exclude locoregional recurrent cases with high risk of ischemia;
• Urine routine examination revealed urine protein ≥ ++, and is proven that 24-h urinary protein volume ≥ 1.0g;
• Patient who has been diagnosed with other malignant carcinoma, excluding cured non-melanoma skin cancer, carcinoma in situ of cervix or papillary thyroid carcinoma;
• Existed meningeal metastasis or central nerve system metastasis;
• HIV positive, TP positive, liver cirrhosis, decompensated liver disease, active hepatitis (active hepatitis that were not well-controlled after treatment (Hepatitis B: HBsAg positive and HBV DNA ≥ 1\*104 copies/ml; Hepatitis C: HCV RNA positive and abnormal hepatic function; the co-infection of hepatitis B and hepatitis C), and need to receive antiviral treatment;
• Patients who had severe hypersensitivity history to other monoclonal antibody;
• Patients who had great difficulty for oral drugs, e.g. cannot swallow, chronic diarrhea and bowel congestion, etc.

Sponsors & Collaborators

• Sun Yat-sen University: lead
• Chia Tai Tianqing Pharmaceutical Group Co., Ltd.: collaborator

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, China

Location

Related Publications (10)

• Yang Y, Qu S, Li J, Hu C, Xu M, Li W, Zhou T, Shen L, Wu H, Lang J, Hu G, Luo Z, Fu Z, Qu S, Feng W, Chen X, Lin S, Zhang W, Li X, Sun Y, Lin Z, Lin Q, Lei F, Long J, Hong J, Huang X, Zeng L, Wang P, He X, Zhang B, Yang Q, Zhang X, Zou J, Fang W, Zhang L. Camrelizumab versus placebo in combination with gemcitabine and cisplatin as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (CAPTAIN-1st): a multicentre, randomised, double-blind, phase 3 trial. Lancet Oncol. 2021 Aug;22(8):1162-1174. doi: 10.1016/S1470-2045(21)00302-8. Epub 2021 Jun 23.

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• Cai, Q. & Su, N. & Fang, Y. & Ma, S. & Xia, Y. & Zhang, X. & Liu, P. & Yang, H.. (2020). 929P Anlotinib in patients with recurrent or metastatic nasopharyngeal carcinoma: An interim analysis of a phase II clinical trial. Annals of Oncology. 31. S668. 10.1016/j.annonc.2020.08.1044.

  BACKGROUND

• Hui EP, Ma BBY, Loong HHF, Mo F, Li L, King AD, Wang K, Ahuja AT, Chan CML, Hui CWC, Wong CH, Chan ATC. Efficacy, Safety, and Pharmacokinetics of Axitinib in Nasopharyngeal Carcinoma: A Preclinical and Phase II Correlative Study. Clin Cancer Res. 2018 Mar 1;24(5):1030-1037. doi: 10.1158/1078-0432.CCR-17-1667. Epub 2018 Jan 4.

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• Yuan M, Zhai Y, Men Y, Zhao M, Sun X, Ma Z, Bao Y, Yang X, Sun S, Liu Y, Zhang W, Hui Z. Anlotinib Enhances the Antitumor Activity of High-Dose Irradiation Combined with Anti-PD-L1 by Potentiating the Tumor Immune Microenvironment in Murine Lung Cancer. Oxid Med Cell Longev. 2022 Feb 1;2022:5479491. doi: 10.1155/2022/5479491. eCollection 2022.

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MeSH Terms

Conditions

Nasopharyngeal Neoplasms

Interventions

penpulimab; Capecitabine

Condition Hierarchy (Ancestors)

Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Jun Ma, M.D.

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

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

Model Details: The combination of anlotinib, penpulimab and capecitabine.

Study Record Dates

• First Submitted: March 28, 2023
• First Posted: April 11, 2023
• Study Start: September 1, 2023
• Primary Completion: July 30, 2025
• Study Completion (Estimated): July 1, 2026
• Last Updated: January 23, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)