Apatinib and Camrelizumab in Recurrent or Metastatic Nasopharyngeal Carcinoma With First-line Treatment Failure

Study Overview
=================
Brief Summary
-----------------
This is a prospective phase II clinical trial to evaluate the efficacy and safety of apatinib and camrelizumab in recurrent or metastatic nasopharyngeal carcinoma who failed at least the first-line treatment.

Official Title
-----------------
Apatinib Combined With Camrelizumab in Recurrent or Metastatic Nasopharyngeal Carcinoma Who Failed at Least the First-line Treatment

Conditions
-----------------
Nasopharyngeal Carcinoma, Recurrent Nasopharyngeal Carcinoma, Metastatic Nasopharyngeal Carcinoma, Chemotherapy Effect, Immunotherapy, Molecular Targeted Therapy

Intervention / Treatment
-----------------
* Drug: Apatinib plus Camrelizumab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female; 18-70 years of age. Subjects diagnosed with pathological confirmed metastatic nasopharyngeal carcinoma, or subjects with recurrent NPC that is unfit for local treatment Underwent at least first-line treatment failure ECOG performance status of 0 or 1. Life expectancy more than 12 weeks. Subjects enrolled must have measurable lesion(s) according to response evaluation criteria in solid (RECIST) v1.1. Adequate organ function assessed by laboratory parameters during the screening period. Female subjects agree not to be pregnant or lactating from beginning of the study screening through at least 3 months after receiving the last dose of study treatment. Both men and women of reproductive potential must be willing and able to employ a highly effective method of birth control/contraception to prevent pregnancy. Able to understand and sign an informed consent form (ICF). Exclusion Criteria: Subjects with any active autoimmune disease or history of autoimmune disease, or history of syndrome that requires systemic steroids or immunosuppressive medications, including but not limited to the following: rheumatoid arthritis, pneumonitis, colitis (inflammatory bowel disease), hepatitis, hypophysitis, nephritis, hyperthyroidism, and hypothyroidism, except for subjects with vitiligo or resolved childhood asthma/atopy. Subjects with the following conditions will not be excluded from this study: asthma that requires intermittent use of bronchodilators, hypothyroidism stable on hormone replacement, vitiligo, Graves' disease, or Hashimoto's disease. Additional exceptions may be made with medical monitor approval; Known history of hypersensitivity to any components of the Camrelizumab formulation or other monoclonal antibodies ; 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 4 weeks before study drug administration. Note: corticosteroids used for the purpose of IV contrast allergy prophylaxis are allowed; Subjects who underwent anti-PD-1 /PD-L antibody or anti-CTLA-4 antibody (or any other antibody acting on T cell synergistic stimulation or checkpoint pathway) and anti-angiogenic drugs. Abnormal coagulation function (INR>1.5×ULN, APTT>1.5×ULN) with bleeding tendency. The laboratory test values within 7 days before enrollment do not meet the relevant standards. Active central nervous system (CNS) metastases (indicated by clinical symptoms, cerebral edema, steroid requirement, or progressive disease); Diagnosed with other malignant tumors. Uncontrolled clinically significant medical condition, including but not limited to the following: Hypertension that cannot be reduced to the normal range after antihypertensive drug congestive heart failure (New York Health Authority Class &gt; 2), unstable angina, myocardial infarction within the past 12 months, clinically significant supraventricular arrhythmia or ventricular arrhythmia requiring treatment or intervention; Active bleeding, ulcer, intestinal perforation, major surgery in the previous month; Patients with tumors close to the internal carotid artery or other large vessels, thus at risk of massive bleeding Active infection or an unexplained fever; 38.5°C during screening visits or on the first scheduled day of dosing (at the discretion of the investigator, subjects with tumor fever may be enrolled); History of immunodeficiency including seropositivity for human immunodeficiency virus (HIV), or other acquired or congenital immune-deficient disease; active tuberculosis (TB), anti-TB treatment is ongoing or within 1 year prior to screening; Evidence of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection or risk of reactivation based on institutional guidelines and tests. Testing may include the following: HBV DNA, HCV RNA, hepatitis B surface antigen, or anti-Hepatitis B core antibody. Received any anti-infective vaccine (e.g. influenza vaccine, varicella vaccine, etc.) within 4 weeks prior to enrollment. Any other medical (eg, pulmonary, metabolic, congenital, endocrinal, or CNS disease), psychiatric, or social condition deemed by the investigator to be likely to interfere with a subject's rights, safety, welfare, or ability to sign informed consent, cooperate, and participate in the study or would interfere with the interpretation of the results;

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Apatinib plus Camrelizumab arm<br>Subjects receive apatinib plus camrelizumab | Drug: Apatinib plus Camrelizumab<br>* Subjects receive Apatinib, 250mg, QD and Camrelizumab, 200mg, D1, Q3W. Treatment was continued until confirmed disease progression, death, unacceptable toxicity, withdrawal of consent, or investigator decision.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate | Defined as the proportion of patients whose tumors shrink to complete response (CR) or partial response (PR) and remain for a certain period of time according to RECIST 1.1 | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of patients who achieved disease control | Defined as the proportion of subjects who achieve CR+PR+stable disease (SD) for at least 4 weeks according to RECIST 1.1. | 1 year | 
| The proportion of patients who achieved clinical benefit | Defined as maintaining the efficacy of CR+PR+SD for at least 6 months according to RECIST 1.1. | 1 year | 
| median progression-free survival | Defined as the period from the start of enrollment until disease progression or death from any cause. | 1 year | 
| Duration of response | Defined as the time from the first assessment of CR and PR to the first assessment of PD or death caused by any cause according to RECIST 1.1. | 1 year | 
| Adverse events | NCI-CTC5.0 standard was adopted, and the safety was assessed mainly by clinical laboratory tests, ECOG-PS score, physical examination, electrocardiogram, and adverse event results. | 1 year |