Nasopharyngeal Carcinoma Clinical Trial
Official title:
Efficacy and Safety of Camrelizumab Combined With Apatinib in Patients With First-line Platinum-resistant Recurrent/Metastatic Nasopharyngeal Carcinoma: a Single-center, Single-arm, Phase 2 Trail
The purpose of this study is to explore the efficacy and safety of a combination of Camrelizumab and Apatinib regimen in treating recurrent or metastatic nasopharyngeal carcinoma patients who have failed first-line platinum-based chemotherapy.
Status | Not yet recruiting |
Enrollment | 27 |
Est. completion date | October 2023 |
Est. primary completion date | October 2022 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 75 Years |
Eligibility |
Inclusion Criteria: 1. Histologically or cytologically confirmed with recurrent or metastatic nasopharyngeal carcinoma which is not amenable to curative treatment with surgery and/or radiation therapy. 2. Age = 18 years and = 75 years, both genders. 3. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1. 4. The life expectancy of at least 3 months. 5. Have failed for first-line platinum-based chemotherapy. 6. Patients must have at least 1 lesion that is measurable using RECIST v1.1 criteria. 7. Patients must have adequate organ function (without blood transfusion, without growth factor or blood components support within 14 days before enrollment) as determined by: Absolute neutrophil count (ANC) =1.5×109/L; Platelet count = 75×109/L; Hemoglobin = 9 g/dL; serum total bilirubin (TBIL) =1.5 times the upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =2.5×upper limit of normal (ULN), (for subjects with liver metastases, TBIL =3×ULN; ALT and AST=5×ULN); Creatinine =1.5×ULN or creatinine clearance rate=50 ml/min (Cockcroft-Gault formula); serum albumin =28 g/L; Thyroid-stimulating hormone (TSH) levels =1×ULN (however, patients with free Triiodothyronine [FT3] or free Thyroxine [FT4] levels =1× ULN may be enrolled); INR, APTT=1.5 x ULN. 8. All women with fertility potential must undergo a urine or serum pregnancy test during screening and the results are negative. 9. Written informed consent. Exclusion Criteria: 1. Known history of hypersensitivity to any components of the Camrelizumab formulation, or other monoclonal antibodies. 2. Prior exposure to immune checkpoint inhibitors, including anti-PD-1, anti-PD-L1, anti-PD-L2 antibodies. 3. Prior therapy with tyrosine kinase-inhibitor agent targeting at VEGFR. 4. There was a history of severe bleeding, and any bleeding events with a serious grade of 3 or more in CTCAE5.0 occurred within 4 weeks before screening. 5. Before treatment, MRI showed that the tumor may have invaded important blood vessels (such as enclosing the internal carotid artery/ vein), nasopharyngeal necrosis or researchers have determined that the tumor is highly likely to invade important blood vessels and cause fatal massive bleeding during treatment. 6. Patients with abnormal blood coagulation and bleeding tendency (14 days before signing informed consent: INR is within the normal range without anticoagulant); patients treated with anticoagulants or vitamin K antagonists such as warfarin, heparin or their analogues. On the premise that the INR < 1.5, low-dose warfarin (1mg orally, once a day) or low-dose aspirin (daily dose not more than 100mg) is allowed for preventive purposes. 7. Arteriovenous thrombosis occurred within one year before the screening, such as cerebrovascular accident (including temporary ischemic attack), deep venous thrombosis (except venous thrombosis caused by intravenous catheterization due to early chemotherapy) and pulmonary embolism. 8. Patients with hypertension who cannot be well controlled by antihypertensive therapy (systolic blood pressure = 140mmHg, diastolic blood pressure = 90mmHg); patients with a history of hypertensive crisis or hypertensive encephalopathy. 9. Proteinuria = (++) or 24 hours total urine protein > 1.0 g. 10. Received any CYP3A4 inhibitor within 2 weeks before the first administration. 11. Have a history of Crohn's disease, ulcerative colitis, and chronic diarrhea. 12. Have a history of gastrointestinal perforation or fistula. 13. Any factors that affect oral drug. 14. Prior malignancy active within the previous 5 years except for locally curable cancers that have been apparently cured, such as basal cell skin cancer or carcinoma in situ of the cervix. 15. Join another clinical study at the same time, received any research drug within 4 weeks before the first administration of the drug. 16. Patients with any active autoimmune disease or a documented history of autoimmune disease such as pneumonia, colitis, hepatitis, nephritis, hyperthyroidism or hypothyroidism; 17. Concurrent medical condition requiring the use of immunosuppressive medications, or immunosuppressive doses of systemic or absorbable topical corticosteroids. Doses > 10 mg/day prednisone or equivalent are prohibited within 2 weeks before study drug administration. 18. History of immunodeficiency including seropositivity for human immunodeficiency virus (HIV), or other acquired or congenital immune-deficient disease. 19. Be known to have active tuberculosis. 20. Hepatitis B virus (HBV) >2000 IU/ml or DNA = 1×10^4/ml; or hepatitis C virus (HCV) RNA = 1×10^3/ml). 21. Has an active infection requiring systemic therapy. 22. Has known active central nervous system metastases. 23. Severe, uncontrolled angiocardiopathy (heart failure > class II NYHA, unstable angina, myocardial infarction within past 1 year, supraventricular or ventricular arrhythmia which need medical intervention, or QT interval male = 450 ms, female = 470 ms.). 24. Have been vaccinated with anti-tumor vaccines or have been vaccinated with live vaccines within 4 weeks before screening. 25. Pregnant or nursing. 26. Underlying medical condition that, in the Investigator's opinion, would increase the risks of study drug administration or obscure the interpretation of toxicity determination or adverse events. |
Country | Name | City | State |
---|---|---|---|
China | Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center | Guangzhou | Guangdong |
Lead Sponsor | Collaborator |
---|---|
Sun Yat-sen University |
China,
Fang W, Yang Y, Ma Y, Hong S, Lin L, He X, Xiong J, Li P, Zhao H, Huang Y, Zhang Y, Chen L, Zhou N, Zhao Y, Hou X, Yang Q, Zhang L. Camrelizumab (SHR-1210) alone or in combination with gemcitabine plus cisplatin for nasopharyngeal carcinoma: results from two single-arm, phase 1 trials. Lancet Oncol. 2018 Oct;19(10):1338-1350. doi: 10.1016/S1470-2045(18)30495-9. Epub 2018 Sep 10. — View Citation
Hsu C, Lee SH, Ejadi S, Even C, Cohen RB, Le Tourneau C, Mehnert JM, Algazi A, van Brummelen EMJ, Saraf S, Thanigaimani P, Cheng JD, Hansen AR. Safety and Antitumor Activity of Pembrolizumab in Patients With Programmed Death-Ligand 1-Positive Nasopharyngeal Carcinoma: Results of the KEYNOTE-028 Study. J Clin Oncol. 2017 Dec 20;35(36):4050-4056. doi: 10.1200/JCO.2017.73.3675. Epub 2017 Aug 24. — View Citation
Lan CY, Wang Y, Xiong Y, Li JD, Shen JX, Li YF, Zheng M, Zhang YN, Feng YL, Liu Q, Huang HQ, Huang X. Apatinib combined with oral etoposide in patients with platinum-resistant or platinum-refractory ovarian cancer (AEROC): a phase 2, single-arm, prospective study. Lancet Oncol. 2018 Sep;19(9):1239-1246. doi: 10.1016/S1470-2045(18)30349-8. Epub 2018 Aug 3. Erratum in: Lancet Oncol. 2018 Sep;19(9):e440. — View Citation
Li J, Qin S, Xu J, Xiong J, Wu C, Bai Y, Liu W, Tong J, Liu Y, Xu R, Wang Z, Wang Q, Ouyang X, Yang Y, Ba Y, Liang J, Lin X, Luo D, Zheng R, Wang X, Sun G, Wang L, Zheng L, Guo H, Wu J, Xu N, Yang J, Zhang H, Cheng Y, Wang N, Chen L, Fan Z, Sun P, Yu H. Randomized, Double-Blind, Placebo-Controlled Phase III Trial of Apatinib in Patients With Chemotherapy-Refractory Advanced or Metastatic Adenocarcinoma of the Stomach or Gastroesophageal Junction. J Clin Oncol. 2016 May 1;34(13):1448-54. doi: 10.1200/JCO.2015.63.5995. Epub 2016 Feb 16. — View Citation
Ma BBY, Lim WT, Goh BC, Hui EP, Lo KW, Pettinger A, Foster NR, Riess JW, Agulnik M, Chang AYC, Chopra A, Kish JA, Chung CH, Adkins DR, Cullen KJ, Gitlitz BJ, Lim DW, To KF, Chan KCA, Lo YMD, King AD, Erlichman C, Yin J, Costello BA, Chan ATC. Antitumor Activity of Nivolumab in Recurrent and Metastatic Nasopharyngeal Carcinoma: An International, Multicenter Study of the Mayo Clinic Phase 2 Consortium (NCI-9742). J Clin Oncol. 2018 May 10;36(14):1412-1418. doi: 10.1200/JCO.2017.77.0388. Epub 2018 Mar 27. Erratum in: J Clin Oncol. 2018 Aug 1;36(22):2360. — View Citation
Reck M, Mok TSK, Nishio M, Jotte RM, Cappuzzo F, Orlandi F, Stroyakovskiy D, Nogami N, Rodríguez-Abreu D, Moro-Sibilot D, Thomas CA, Barlesi F, Finley G, Lee A, Coleman S, Deng Y, Kowanetz M, Shankar G, Lin W, Socinski MA; IMpower150 Study Group. Atezolizumab plus bevacizumab and chemotherapy in non-small-cell lung cancer (IMpower150): key subgroup analyses of patients with EGFR mutations or baseline liver metastases in a randomised, open-label phase 3 trial. Lancet Respir Med. 2019 May;7(5):387-401. doi: 10.1016/S2213-2600(19)30084-0. Epub 2019 Mar 25. — View Citation
Xu J, Zhang Y, Jia R, Yue C, Chang L, Liu R, Zhang G, Zhao C, Zhang Y, Chen C, Wang Y, Yi X, Hu Z, Zou J, Wang Q. Anti-PD-1 Antibody SHR-1210 Combined with Apatinib for Advanced Hepatocellular Carcinoma, Gastric, or Esophagogastric Junction Cancer: An Open-label, Dose Escalation and Expansion Study. Clin Cancer Res. 2019 Jan 15;25(2):515-523. doi: 10.1158/1078-0432.CCR-18-2484. Epub 2018 Oct 22. — View Citation
Zhang L, Huang Y, Hong S, Yang Y, Yu G, Jia J, Peng P, Wu X, Lin Q, Xi X, Peng J, Xu M, Chen D, Lu X, Wang R, Cao X, Chen X, Lin Z, Xiong J, Lin Q, Xie C, Li Z, Pan J, Li J, Wu S, Lian Y, Yang Q, Zhao C. Gemcitabine plus cisplatin versus fluorouracil plus cisplatin in recurrent or metastatic nasopharyngeal carcinoma: a multicentre, randomised, open-label, phase 3 trial. Lancet. 2016 Oct 15;388(10054):1883-1892. doi: 10.1016/S0140-6736(16)31388-5. Epub 2016 Aug 23. Erratum in: Lancet. 2016 Oct 15;388(10054):1882. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Objective response rate | An objective response is defined as either a confirmed CR or a PR, as determined by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST1.1) from the National Cancer Institute (NCI) | 2 years | |
Secondary | Disease control rate | A disease control rate is defined as either a confirmed CR or a PR or a SD, as determined by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST1.1) from the National Cancer Institute (NCI). | 2 years | |
Secondary | Duration of response | Defined from date of first confirmed CR or a PR to date of first documentation of progression or death due to any cause, as determined by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST1.1) from the National Cancer Institute (NCI). | 2 years | |
Secondary | Progression-free survival rate | Defined from date of registration to date of first documentation of progression or death due to any cause. | 2 years | |
Secondary | Overall survival rate | Defined from date of registration to date of first documentation of death from any cause or censored at the date of the last follow-up. | 2 years | |
Secondary | Incidence rate of adverse events (AEs) | Analysis of acute and late adverse events (AEs) are evaluated. Numbers of patients of treatment-related adverse events (acute toxicity) as assessed by CTCAE v5.0. | 2 years | |
Secondary | PD-L1 expression on tumor and immune cells | The efficacy of the combination of Camrelizumab and apatinib as measured by objective response, will be described in patients according to PD-L1 positive and PD-L1 negative. | 2 years | |
Secondary | VEGFR-2 expression in tumor | The impact of VEGFR-2 on efficacy of the combination of Camrelizumab and apatinib will be explored. | 2 years |
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT05979961 -
Phase III Trial of Concurrent Chemotherapy Alone in Patients With Low-risk Nasopharyngeal Carcinoma
|
Phase 3 | |
Active, not recruiting |
NCT04242199 -
Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of INCB099280 in Participants With Advanced Solid Tumors
|
Phase 1 | |
Recruiting |
NCT05415098 -
Study of Safety, Pharmacokinetic and Efficacy of APG-5918 in Advanced Solid Tumors or Lymphomas
|
Phase 1 | |
Recruiting |
NCT06055816 -
Gemcitabine Combined With Endostar and Envafolimab in Elderly Patients With Locally Advanced Nasopharyngeal Carcinoma
|
Phase 2 | |
Recruiting |
NCT05547971 -
Development of Intelligent Model for Radioactive Brain Damage of Nasopharyngeal Carcinoma Based on Radio-metabolomics
|
||
Not yet recruiting |
NCT05020925 -
SHR-1701 in Combination With Famitinib in Patients With Recurrent/Metastatic Nasopharyngeal Carcinoma
|
Phase 1/Phase 2 | |
Not yet recruiting |
NCT04548271 -
Camrelizumab Combined With Apatinib in Patients With PD-1 Antagonists Resistant Recurrent/Metastatic Nasopharyngeal Carcinoma
|
Phase 2 | |
Recruiting |
NCT02795169 -
Trail Evaluating Carbon Ion Radiotherapy With Concurrent Chemotherapy for Locally Recurrent Nasopharyngeal Carcinoma
|
Phase 1/Phase 2 | |
Terminated |
NCT02801487 -
Trial Evaluating Carbon Ion Radiotherapy With Concurrent Chemotherapy for Locally Recurrent Nasopharyngeal Carcinoma
|
Phase 1/Phase 2 | |
Terminated |
NCT02569788 -
Trail Evaluating Carbon Ion Radiotherapy for Locally Recurrent Nasopharyngeal Carcinoma
|
Phase 1/Phase 2 | |
Completed |
NCT02237924 -
Endostar Combined With Intensity-modulated Radiotherapy Compare With Chemoradiation for Nasopharyngeal Carcinoma
|
Phase 2 | |
Recruiting |
NCT02044562 -
Dietary Nitrate on Plasma Nitrate Levels for Nasopharyngeal Carcinoma Patients
|
N/A | |
Terminated |
NCT01694576 -
NPC Staged N2-3M0:Adjuvant Chemotherapy or Just Observation After Concurrent Chemoradiation
|
Phase 2 | |
Recruiting |
NCT01462903 -
A Study of Adoptive Immunotherapy With Autologous Tumor Infiltrating Lymphocytes in Solid Tumors
|
Phase 1 | |
Completed |
NCT01271439 -
Study of Chemoradiotherapy Combined With Cetuximab in Nasopharyngeal Carcinoma
|
Phase 2 | |
Completed |
NCT00535795 -
Phase III: Assess Conventional RT w/ Conventional Plus Accelerated Boost RT in the Treatment of Nasopharyngeal CA
|
Phase 3 | |
Completed |
NCT00379262 -
Therapeutic Gain by Induction-concurrent Chemoradiotherapy and/or Accelerated Fractionation for Nasopharyngeal Carcinoma
|
Phase 3 | |
Completed |
NCT03398980 -
Late Sequelae of Childhood and Adolescent Nasopharyngeal Carcinoma Survivors After Radiotherapy
|
N/A | |
Completed |
NCT01309633 -
Study Evaluating Two Loading Regimens of Sunitinib or Bevacizumab Alternating With Cisplatin and Gemcitabine as Induction Therapy for Locally Advanced Nasopharyngeal Carcinoma (NPC)
|
Phase 2 | |
Not yet recruiting |
NCT05519956 -
Elective Level Ib Irradiation in Nasopharyngeal Carcinoma Patients Based on the International Guidelines
|
Phase 3 |