An Open-Label, Single Center, Nonrandomized, Phase 1 Study to Evaluate Safety and Efficacy of Using the Combination Treatment of SHR-1210, Gemcitabine and Cis-platinum by Recurrent and Metastatic NPC
Overview
- Phase
- Phase 1
- Intervention
- SHR-1210
- Conditions
- Nasopharyngeal Carcinoma
- Sponsor
- Jiangsu HengRui Medicine Co., Ltd.
- Enrollment
- 23
- Locations
- 1
- Primary Endpoint
- progression of disease
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
This is an open-label, single center, non-randomized, phase I trial to evaluate safety and efficacy of using the combination treatment of SHR-1210, gemcitabine and cis-platinum by recurrent and metastatic NPC.
Detailed Description
This is an open-label, single center, nonrandomized, Phase 1 study to evaluate safety and efficacy of using the combination treatment of SHR-1210, gemcitabine and cis-platinum by recurrent and metastatic NPC. The safety of SHR-1210 will be assessed by ongoing reviews of clinical laboratory tests, Eastern Cooperative Oncology Group (ECOG) performance status, physical examination, electrocardiogram (ECG), and adverse events. Evaluations of immune safety will also be conducted (immune-related adverse events (AEs), or labs of autoimmune sera, inflammatory events, and immunogenicity). Safety evaluations (both clinical and laboratory) are performed at baseline, before each study treatment, and throughout the study.Tumor response will be assessed by radiographic examination in screening visit and every 2 cycles after first dose.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male or female 18-70 years of age.
- •Subjects diagnosed with pathological confirmed Primary metastatic nasopharyngeal carcinoma, or subjects with recurrent NPC that is unfit for local treatment.
- •Subjects with recurrent and metastatic NPC who did't receive any Systemic chemotherapy, neoadjuvant chemotherapy, concurrent radiochemotherapy and adjuvant chemotherapy 6 month before first dose are excepted.
- •ECOG performance status of 0 or
- •Life expectancy more than 12 weeks.
- •Subjects enrolled must have measurable lesion(s) according to response evaluation criteria in solid (RECIST) v1.
- •Adequate laboratory parameters during the screening period as evidenced by the following:
- •Absolute neutrophil count ≥1.5\*10E9/L;
- •Platelets ≥100\*10E9/L;
- •Hemoglobin ≥9.0 g/dL;
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 SHR-1210 formulation;
- •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. Note: corticosteroids used for the purpose of IV contrast allergy prophylaxis are allowed;
- •Active central nervous system (CNS) metastases (indicated by clinical symptoms, cerebral edema, steroid requirement, or progressive disease);
- •Uncontrolled clinically significant medical condition, including but not limited to the following:
- •congestive heart failure (New York Health Authority Class \> 2),
- •unstable angina,
- •myocardial infarction within the past 12 months, or
- •clinically significant supraventricular arrhythmia or ventricular arrhythmia requiring treatment or intervention;
- •Active infection or an unexplained fever; 38.5℃ during screening visits or on the first scheduled day of dosing (at the discretion of the investigator, subjects with tumor fever may be enrolled);
Arms & Interventions
SHR-1210, gemcitabine and cis-platinum
Subjects receive SHR-1210 200mg (Day 1) and gemcitabine 1000mg/m2 (Day 1 and Day 8)and cis-platinum 80mg/m2 (Day 1) of each 21-day cycle for at most 6 cycles, followed by SHR-1210 200mg every three weeks (Q3W) maintenance for the remainder of the study or until documented PD.
Intervention: SHR-1210
SHR-1210, gemcitabine and cis-platinum
Subjects receive SHR-1210 200mg (Day 1) and gemcitabine 1000mg/m2 (Day 1 and Day 8)and cis-platinum 80mg/m2 (Day 1) of each 21-day cycle for at most 6 cycles, followed by SHR-1210 200mg every three weeks (Q3W) maintenance for the remainder of the study or until documented PD.
Intervention: Gemcitabine
SHR-1210, gemcitabine and cis-platinum
Subjects receive SHR-1210 200mg (Day 1) and gemcitabine 1000mg/m2 (Day 1 and Day 8)and cis-platinum 80mg/m2 (Day 1) of each 21-day cycle for at most 6 cycles, followed by SHR-1210 200mg every three weeks (Q3W) maintenance for the remainder of the study or until documented PD.
Intervention: cis-platinum
Outcomes
Primary Outcomes
progression of disease
Time Frame: 28 days
progression of disease by radiographic examination