Camrelizumab Combined With Apatinib in Patients With PD-1 Antagonists Resistant Recurrent/Metastatic Nasopharyngeal Carcinoma

NCT04548271 | Unknown Phase 2

• 1 other identifier: B2020-187
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to explore the efficacy and safety of combination of Apatinib and Camrelizumab regimen in treating recurrent or metastatic nasopharyngeal carcinoma patients who were resistant to PD-1 antagonists.

Conditions

Nasopharyngeal Carcinoma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Disease control rate

  2 years

• Duration of response

  2 years

• Progression-free survival rate

  2 years

• Overall survival rate

  2 years

• Incidence rate of adverse events (AEs)

  2 years

Study Arms (1)

Camrelizumab+Apatinib

EXPERIMENTAL

Patients with recurrent or metastatic nasopharyngeal carcinoma who failed to first-line platinum-based chemotherapy and had prior treatment with PD-1 antagonists. Every patients will receive apatinib 250mg orally every day starting 14 days prior to Camrelizumab. Then apatinib 250mg orally every day and Camrelizumab 200mg iv every 3 weeks until disease progression or intolerance of side effects.

Drug: Camrelizumab; Drug: Apatinib

Interventions

Camrelizumab DRUG

Anti-PD-1 targeted immunotherapy

Also known as: SHR-1210

Camrelizumab+Apatinib

Apatinib DRUG

A small-molecule vascular endothelial growth factors receptor (VEGFR) tyrosine kinase inhibitor

Also known as: Apatinib Mesylate

Camrelizumab+Apatinib

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed with recurrent or metastatic nasopharyngeal carcinoma which is not amenable to curative treatment with surgery and/or radiation therapy.
• Age ≥ 18 years and ≤ 75 years, both genders.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1.
• Life expectancy of at least 3 months.
• Have failed for first-line platinum-based chemotherapy.
• Have failed for prior treatment with PD-1 antagonists +/- chemotherapy.
• Patients must have at least 1 lesion that is measurable using RECIST v1.1 criteria.
• 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.
• All women with fertility potential must undergo a urine or serum pregnancy test during screening and the results are negative.
• Written informed consent.

You may not qualify if:

• Known history of hypersensitivity to any components of the Camrelizumab formulation, or other monoclonal antibody.
• Prior therapy with tyrosine kinase-inhibitor agent targeting at VEGFR.
• 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.
• 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.
• 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.
• Arteriovenous thrombosis occurred within one year before 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.
• 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.
• Proteinuria ≥ (++) or 24 hours total urine protein \> 1.0 g.
• Received any CYP3A4 inhibitor within 2 weeks before the first administration.
• Have a history of Crohn's disease, ulcerative colitis, and chronic diarrhea.
• Have a history of gastrointestinal perforation or fistula.
• Any factors that affect the oral drug.
• 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.
• Join another clinical study at the same time, received any research drug within 4 weeks before the first administration of the drug.
• Patients with any active autoimmune disease or a documented history of autoimmune disease such as pneumonia, colitis, hepatitis, nephritis, hyperthyroidism or hypothyroidism;

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

Location

Related Publications (9)

• 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.

  PMID: 27567279 BACKGROUND

• 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.

  PMID: 28837405 BACKGROUND

• 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.

  PMID: 29584545 BACKGROUND

• 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.

  PMID: 30213452 BACKGROUND

• 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.

  PMID: 26884585 BACKGROUND

• 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.

  PMID: 30082170 BACKGROUND

• Reck M, Mok TSK, Nishio M, Jotte RM, Cappuzzo F, Orlandi F, Stroyakovskiy D, Nogami N, Rodriguez-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.

  PMID: 30922878 BACKGROUND

• 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.

  PMID: 30348638 BACKGROUND

• Yuan L, Jia GD, Lv XF, Xie SY, Guo SS, Lin DF, Liu LT, Luo DH, Li YF, Deng SW, Guo L, Zeng MS, Cai XY, Liu SL, Sun XS, Li XY, Li SC, Chen QY, Tang LQ, Mai HQ. Camrelizumab combined with apatinib in patients with first-line platinum-resistant or PD-1 inhibitor resistant recurrent/metastatic nasopharyngeal carcinoma: a single-arm, phase 2 trial. Nat Commun. 2023 Aug 14;14(1):4893. doi: 10.1038/s41467-023-40402-x.

  PMID: 37580352 DERIVED

MeSH Terms

Conditions

Nasopharyngeal Carcinoma

Interventions

camrelizumab; apatinib

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Nasopharyngeal Neoplasms; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases

Central Study Contacts

Haiqiang Mai

CONTACT

86-20-87343380; maihq@sysucc.org.cn

Linquan Tang

CONTACT

86-20-87343380; tanglq@sysucc.org.cn

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: Director of the Department of Nasopharyngeal Carcinoma

Study Record Dates

• First Submitted: September 7, 2020
• First Posted: September 14, 2020
• Study Start: September 1, 2020
• Primary Completion: October 1, 2022
• Study Completion: October 1, 2023
• Last Updated: September 14, 2020

Record last verified: 2020-09

Locations

CN (1)