Brief Title
Apatinib Combined With PD-1 in the Treatment of Recurrent or Metastatic Nasopharyngeal Carcinoma
Official Title
A Prospective Multicenter Phase II Clinical Trial of Apatinib Mesylate Tablets Combined With PD-1 in the Treatment of Recurrent or Metastatic Nasopharyngeal Carcinoma
Brief Summary
The study is to evaluate the clinical efficacy of apatinib mesylate tablets combined with
PD-1 in the treatment of recurrent and metastatic nasopharyngeal carcinoma after IMRT with
concurrent chemotherapy,including The Overall Response Rate (ORR), Progression-free survival
(PFS),Overall survival (OS),and Toxicities.
Detailed Description
PRIMARY OBJECTIVES:
To determine the clinical efficacy of apatinib mesylate tablets combined with PD-1 in the
treatment of recurrent and metastatic nasopharyngeal carcinoma.
SECONDARY OBJECTIVES:
Ⅰ.To explore the adjuvant medication regimen of recurrent and metastatic nasopharyngeal
carcinoma.
Ⅱ.Provide high-level evidence-based medical evidence for the new individualized treatment
strategy of nasopharyngeal carcinoma patients.
OUTLINE:
Eligible patients begin to use apatinib mesylate tablets and PD-1, apatinib mesylate tablets
at the recommended dose of 250mg,orally, QD, continuous administration, 4 weeks (28 days) as
an observation cycle. Until the disease progressed or unbearable adverse reactions appeared.
If missed medication occurs during the medication period, it is confirmed that the next
medication time is less than 12 hours, then there will be no replenishment. The recommended
dose of PD-1 is 200mg/time, Q2W, intravenous injection, 4 weeks (28 days) as an observation
cycle, until disease progression or intolerable toxicity.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Overall Response Rate (ORR)
Secondary Outcome
Progression-free survival (PFS)
Condition
Nasopharyngeal Carcinoma
Intervention
Apatinib mesylate tablet
Study Arms / Comparison Groups
Apatinib combined with PD-1
Description: Eligible patients begin to use apatinib mesylate tablets and PD-1, apatinib mesylate tablets at the recommended dose of 250mg,oral, QD, continuous administration, 4 weeks (28 days) as an observation cycle. Until the disease progressed or unbearable adverse reactions appeared. If missed medication occurs during the medication period, it is confirmed that the next medication time is less than 12 hours, then there will be no replenishment. The recommended dose of PD-1 is 200mg/time, Q2W, intravenous injection, 4 weeks (28 days) as an observation cycle, until disease progression or intolerable toxicity.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
25
Start Date
May 1, 2020
Completion Date
May 30, 2022
Primary Completion Date
May 30, 2021
Eligibility Criteria
Inclusion Criteria:
1. Male or female patients: 18-70 years old.
2. Pathologically diagnosed nasopharyngeal carcinoma.
3. Patients with nasopharyngeal carcinoma who have local recurrence after one
comprehensive treatment (clinical examination found definite local residual: clear
residual or cervical enlarged lymph node can be seen under electronic
nasopharyngoscope).
4. Patients with nasopharyngeal carcinoma who have distant metastasis after one
comprehensive treatment (found distant metastasis by liver ultrasound, chest X-ray,
bone scan or other examination (such as CT, MRI or PET/CT) as the clinician considers
appropriate.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
6. Estimated survival ≥6 months.
7. The function of the main organs is good, that is, one week before joining the group,
the following requirements are met:
Blood routine examination:Hemoglobin > 80 g/L(no blood transfusion within 14
days);Neutrophils count > 1.5x10^9/L;Platelet count > 80x10^9/L; biochemical
test:serum total bilirubin ≤1.5×ULN(upper limit of normal), ALT or
AST≤3×ULN;Endogenous creatinine clearance ≥ 1.5×ULN;Acceptable clotting state: the
international standardized ratio ((INR)), prothrombin time (PT) and activated partial
thromboplastin time (APTT) of blood clots were less than 1.5 times of the upper limit
of normal (ULN).
8. All women with fertility potential must undergo a urine or serum pregnancy test during
screening and the results are negative.
9. The subjects voluntarily joined the study, signed the informed consent form, had good
compliance and cooperated with the follow-up.
Exclusion Criteria:
1. Before treatment, MRI showed that the tumor may have invaded important blood vessels
(such as enclosing the internal carotid artery / vein), or researchers have determined
that the tumor is highly likely to invade important blood vessels and cause fatal
massive bleeding during treatment.
2. There was a history of severe bleeding, and any bleeding events with a serious grade
of 3 or more in CTCAE4.0 occurred within 4 weeks before screening.
3. Patients with hypertension who cannot be well controlled by antihypertensive therapy
alone (systolic blood pressure > 140mmHg, diastolic blood pressure > 90mmHg); patients
with a history of unstable angina pectoris; patients newly diagnosed with angina
pectoris within 3 months or myocardial infarction within 6 months before screening;
arrhythmias (including QTcF: ≥ 450ms in males, ≥ 470ms in females) require long-term
use of antiarrhythmic drugs and New York Heart Association grade ≥ II cardiac
insufficiency.
4. Positive urine protein.
5. 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 international standardized ratio of
prothrombin time ((INR)) is less than 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.
6. 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.
7. Long-term unhealed wound or incomplete fracture.
8. Any factors that affect the oral drug, such as inability to swallow, chronic diarrhea
and intestinal obstruction, etc.
9. For female subjects: women of childbearing age, it is not acceptable to use medically
approved contraception during the study treatment period and within 6 months after the
end of the study treatment period;Patients with positive serum or urine pregnancy
test;Nursing patients.Male subjects: patients who did not undergo surgical
sterilization or did not agree to use medically approved contraception during the
study and within 6 months after the study.
10. Having a history of psychotropic substance abuse and unable to quit or having mental
disorders.
11. Medical history of immunodeficiency, or other acquired, congenital immunodeficiency
disease, or history of organ transplantation.Any symptomatic autoimmune disease (such
as lupus, scleroderma, Crohn's disease, ulcerative colitis) that requires
administration of >10mg of prednisone equivalent. Lower dose steroids for conditions
such as hypophysitis are allowed.
12. Any serious harm to the subject's safety or evidence of significant medical illness
that in the investigator's judgment will substantially increase the risk associated
with the subject's participation in and completion of the study.
13. Any prior severe adverse event attributed to prior anti-PD1 therapy that, in the
Principal investigator's opinion, would contraindicate pembrolizumab administration
such as:Grade 2 or higher pneumonitis、Grade 4 AST or ALT elevation、Grade 3 or higher
colitis; Known active infection with Hepatitis B Virus (HBV), Hepatitis C Virus (HCV),
or HIV. Cleared HBV/HCV infection is not an exclusion, nor is HIV infection with
cluster of differentiations 4 (CD4) counts >500 and an undetectable viral load.
14. Active bacterial, viral, or fungal infections, requiring systemic therapy apart from
anti-viral maintenance therapy for HIV；or Uncontrolled activity infected.
Gender
All
Ages
18 Years - 70 Years
Accepts Healthy Volunteers
No
Contacts
Wei Jiang, Ph.D., +86-773-2882906, [email protected]
Location Countries
China
Location Countries
China
Administrative Informations
NCT ID
NCT04350190
Organization ID
GLMU-06
Responsible Party
Sponsor-Investigator
Study Sponsor
Wei Jiang
Collaborators
Wuzhou Red Cross Hospital
Study Sponsor
Wei Jiang, Ph.D., Study Director, Guilin Medical University, China
Verification Date
April 2020