Anlotinib, Penpulimab and Capecitabine in Recurrent/Metastatic Nasopharyngeal Carcinoma

Nasopharyngeal Neoplasms Clinical Trial

— ALTER-HN005  

Official title:

The First-line Therapy With the Combination of Anlotinib, Penpulimab and Capecitabine in Recurrent/Metastatic Nasopharyngeal Carcinoma: a Single-arm, Open-label, Phase II Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05807880
• Other study ID #: ALTER-HN005
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: October 1, 2023
• Est. completion date: October 1, 2025

Study information

• Verified date: September 2023
• Source: Sun Yat-sen University
• Contact: Jun Ma, M.D.
• Phone: +862087343469
• Email: majun[@]sysucc.org.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

The trial is an open-label, single-arm, phase II clinical trial. This trial plans to enroll patient that is diagnosed with locoregionally advanced nasopharyngeal carcinoma at his/her first diagnosis, and has recurrence/metastasis at least 6 months after completing radiotherapy and chemotherapy for the primary lesion, and has never accepted systemic treatment for recurrent/metastatic lesion before. The first-line treatment is the three-drug treatment plan, including anlotinib, penpulimab and capecitabine, for 4-6 cycles. Then a maintenance treatment will be run, including penpulimab and capecitabine, until PD or intolerance to toxicity.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 110
• Est. completion date: October 1, 2025
• Est. primary completion date: October 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

Participants will be included only when they meet all inclusion criteria.

• 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:

1. 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.):

1. Hemoglobin (HB) = 90g/L;

2. White blood cell (WBC) = 4*109/L;

3. Blood platelet (PLT): 100_109/L;

2. Biochemistry examination should meet:

1. Total bilirubin (TBIL) = 1.5*upper limit of normal (ULN);

2. Alanine transaminase (ALT) and aspartate transaminase (AST) = 2.5*ULN;

3. Serum creatinine (Cr) = 1.5×ULN and creatinine clearance (CCr) = 60ml/min;

3. Coagulation function: INR and APTT = 1.5*ULN;

4. Myocardial injury, heart failure three indexes examination, electrocardiogram results are normal; For patients with abnormalities in these three examinations, the researchers will assess whether to add Doppler ultrasound.

5. Thyroid gland function: TSH = ULN; If not, including those whose FT3 and FT4 levels are normal, and excluding others.

• Fertile women must already used reliable contraceptive measures or have negative gestational test (serum) result within the 7 days before inclusion. And they are willing to take suitable contraceptive measures during the clinical trial and the 8 weeks after the last administration of intervention or have sterilized. Men must take suitable contraceptive measures during the clinical trial and the 8 weeks after the last administration of intervention or have been surgically sterilized.
• Patient has signed the informed consent and has good compliance. Exclusion Criteria:

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.).
• Patients who had active or uncontrolled severe infection (= CTCAE level 3 infection) within the 4 weeks before inclusion;
• 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;
• Patients who had = level I myocardial ischemia, myocardial infarction, arrythmia (including QTc = 480ms) or = level 2 congestive heart failure (New York Heart Association, NYHA) during the 6 months before inclusion.
• If the patient need Doppler ultrasound examination (the 4th of inclusion criteria 5), the abnormal result is when left ventricular ejection fraction (LVEF) < lower limit of normal (60%);
• 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 have participated in other anti-tumor drug-related clinical trial in the 4 weeks before inclusion;
• Patients who have received attenuated live vaccine or AK-105 treatment in the 30 days before inclusion;
• 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.
• Patients with mental drug abuse history and cannot withdrawal or mental disorder;
• There are conditions that, in the investigator's judgment, seriously endanger patient safety, may confuse the study results, or concomitant diseases or any other situations that affect the patient's completion of the study.

Related Conditions & MeSH terms

• Nasopharyngeal Carcinoma
• Nasopharyngeal Neoplasms

Intervention

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

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Sun Yat-sen University	Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

References & Publications (10)

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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.

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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. — View Citation

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Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival (PFS)	Progression-free survival is measured according to the RECIST 1.1.	3-year
Secondary	Objective remission rate (ORR)	Objective remission rate is measured according to the RECIST 1.1.	Median value
Secondary	Progression-free survival (PFS)	Progression-free survival is measured according to the iRECIST.	3-year
Secondary	Overall survival (OS)	Overall survival is measured from day of diagnosis until death due to any cause or the latest known date alive.	3-year
Secondary	Quality of Life (QoL)	Quality of Life is measured by the Quality of Life Questionnaire-Core 30 module (QLQ-C30) designed by European Organisation for Research and Treatment of Cancer (EORTC).	3-year
Secondary	Quality of Life (QoL)	Quality of Life is measured by the FACT-H&N designed by The Center on Outcomes Research and Education.	3-year
Secondary	Incidence of toxicities	Incidence of toxicities are measured by questionnaires covering adverse effect (AE), severe adverse effect (SAE), treatment-related adverse effect (TRAE), treatment-related severe adverse effect (TRSAE), immune-related adverse effect, immune-related treatment-related adverse effect according to NCI-CTC AE V5.0.	3-year