Gemcitabine and Cisplatin With/Without Anlotinib in Advanced Nasopharyngeal Carcinoma

Brief Title

Gemcitabine and Cisplatin With/Without Anlotinib in Advanced Nasopharyngeal Carcinoma

Official Title

Phase III Randomized Trial of Anlotinib Plus Gemcitabine/Cisplatin Vesus Placebo Plus Gemcitabine/Cisplatin in Previous Untreated Patients With Recurrent/Metastatic Nasopharyngeal Carcinoma

Brief Summary

      This is a Phase III randomized controlled multi-center trial comparing anlotinib plus
      Gemcitabine/Cisplatin with placebo plus Gemcitabine/Cisplatin in previous untreated patients
      with recurrent/metastatic Nasopharyngeal Carcinoma, in order to verify the efficacy and
      security of anlotinib in mNPC patients.
    

Study Phase

Phase 3

Study Type

Interventional

Primary Outcome

PFS

Condition

Nasopharyngeal Carcinoma

Intervention

Gemcitabine/Cisplatin

Study Arms / Comparison Groups

 anlotinib plus Gemcitabine/Cisplatin

Description:  patients receive anlotinib at 12mg QD (d1-d14)and gemcitabine (1000 mg/m² d1,8) or cisplatin (80mg/m² d1) every 3 weeks for every cycle

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Drug

Estimated Enrollment

336

Start Date

August 27, 2018

Completion Date

July 30, 2021

Primary Completion Date

July 30, 2020

Eligibility Criteria

        Inclusion Criteria:

          1. Informed of the investigational nature of this study and give written informed consent

          2. Histologically or cytologically confirmed nasopharyngeal carcinoma, tumor staged as
             IVB (according to the 8th AJCC edition) or recurrent tumor nott suitable for local
             treatment.

          3. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 to1, life
             expectancy of at least 12 weeks.

          4. Antitumor therapy naive for recurrent or metastatic nasopharyngeal carcinoma

          5. Completed radiotherapy for local tumor 4 weeks before the enrollment

          6. Measurable disease other than brain metastasis based on Response Evaluation Criteria
             in Solid Tumors (RECIST) version 1.1

          7. Adequate organ system function, defined as follows:

               1. ANC ≥1.5×109/L, PLT ≥100×109/L, Hb）≥90g /L;

               2. TBIL ≤ 1.5×ULN；Aminopherases (ALT and AST) ≤ 2.5 × ULN (without liver metastasis)
                  or ≤ 5.0 × ULN (with liver metastasis), Creatinine ≤ 1.5 × ULN or creatinine
                  clearance ≥ 50 ml/min;

               3. Urine protein < ++，or urine protein ≥ ++ concomitant with content of -hour
                  urinary protein <1.0 g;

               4. INR≤1.5×ULN, APTT≤1.5×ULN;

               5. LVEF ≥50%;

          8. Women who are not of child-bearing potential, and women of child-bearing potential who
             have a negative serum or urine pregnancy test prior to initial trial treatment, and
             who agree to use adequate contraceptive measures during the study; Men with partners
             of childbearing potential willing to use adequate contraceptive measures during the
             study

        Exclusion Criteria:

          1. Patients with a previous malignancy within the past 5 years (other than curatively
             treated in situ carcinoma of the cervix, non-melanoma skin cancer and superficial
             bladder carcinoma).

          2. Allergic to anotinib or the chemotherapeutic agents involved in this trial;

          3. Supposed to receive locally treatment (except for those with symptomatic bone
             metastases receive appropriate local doses radiotherapy which does not affect the
             hemogram)

          4. Patients that have received definitive radiotherapy, adjuvant chemotherapy or
             cocurrent chemoradiotherapy for stage I-IVA and developed recurrent disease within 6
             months;

          5. Patients that have previously received target therapies;

          6. Patients that have previously received immunotherapy (i.e.,interferon, or IL-2 ) 28
             days before randomization or within 5 half-life of the drug.

          7. Patients that have previously received immunosupressive drugs (i.e., Corticosteroids,
             cyclophosphamide, azathioprine, methotrexate, thalidomide or TNF-α)

          8. Symptomatic CNS metastasis (i.e. encephaledema, hormone intervention, or brain
             metastasis progression)

          9. Patients currently have bleeding tendency, including but not limited to
             gastrointestinal bleeding, nasal bleeding, hemoptysis, and persistent bleeding or
             coagulopathy;

         10. Hemoptysis (defined as coughing out or spitting out ≥ 1 teaspoon of blood or small
             blood clots or hemoptysis without sputum) within 28 days before randomization, not
             including bloody sputum.

         11. Radiograph (within 28 days before randomization) showed that the tumor surrounded
             important blood vessels, and the investigators determined that entering the study
             would cause bleeding risk;

         12. Subjects have any of the following severe acute complications:

               1. Unstable angina and/or congestive heart failure or vascular disease (eg, aortic
                  aneurysm requires surgically repaired or peripheral venous thromboembolism)
                  requiring hospitalization within 12 months, or other cardiac impairments
                  (eg,uncontrolled arrhythmias) determined by the investigator, which may affect
                  the evaluation of drug safety; Myocardial infarction or ischemia with ST
                  elevation ≥ 2 mm indicated by ECG;

               2. Arterial thromboembolism, venous thromboembolism in grade 3 or higher (according
                  to NCI-CTCAE), transient ischemic attack (TIA), cerebral vascular accident (CVA),
                  transmural myocardial infarction ( MI), hypertensive crisis or hypertensive
                  encephalopathy within 24weeks;

               3. Chronic Obstructive Pulmonary Disease (COPD) or other respiratory diseases
                  requiring hospitalization within 28 days before randomization;

               4. Abdominal fistula, gastrointestinal perforation, intra-abdominal abscess, or
                  acute gastrointestinal bleeding within 24 weeks before randomization;

               5. Esophageal and gastric varices, unhealed ulcers, unhealed wounds or fracture
                  within 24 weeks before randomization;

               6. Pulmonary infections and/or acute bacterial or fungal infections requiring
                  intravenous antibiotic therapy

               7. Clinical jaundice and/or coagulation disorders caused by liver dysfunction;

               8. Minor surgical procedures (including catheterization, excluding peripheral
                  venipuncture central vena catheterization) within 2 days of randomization;

         13. The virological test indicates that either of the following 28 days before
             randomization

               1. HBsAg positive and HBV DNA ≥ 1 × 103 copies/L;

               2. Anti-HCV positive

               3. HIV positive

         14. Participation of an anti-tumor clinic trial within 28 days before randomization
      

Gender

All

Ages

18 Years - 70 Years

Accepts Healthy Volunteers

No

Contacts

, , 

Location Countries

China

Location Countries

China

NCT ID

NCT03601975

Organization ID

ALTN-17-III

Responsible Party

Sponsor

Study Sponsor

Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Study Sponsor

, , 

Verification Date

February 2019