An Open-Label, Single Center, Nonrandomized, Phase 1 Study to Evaluate Safety and Efficacy of Gemcitabine Combined With Apatinib and Toripalimab in Recurrent or Metastatic Nasopharyngeal Carcinoma
Overview
- Phase
- Phase 1
- Intervention
- Gemcitabine combined with Aptinib and Toripalimab
- Conditions
- Nasopharyngeal Carcinoma
- Sponsor
- Sun Yat-sen University
- Enrollment
- 41
- Locations
- 1
- Primary Endpoint
- Adverse events
- Last Updated
- 4 years ago
Overview
Brief Summary
This is an open-label, single center, non-randomized, phase I trial to evaluate the safety and efficacy of gemcitabine combined with apatinib and toripalimab in patients with the recurrent or metastatic nasopharyngeal carcinoma.
Detailed Description
This is an open-label, single center, non-randomized, phase I trial to evaluate the safety and efficacy of gemcitabine combined with apatinib and toripalimab in patients with the recurrent or metastatic nasopharyngeal carcinoma. 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
Ming-Yuan Chen
Professor
Sun Yat-sen University
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 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. A highly effective method of contraception is defined as one that results in a low failure rate, that is, less than 1% per year when used consistently and correctly
- •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 Toripalimab 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,
- •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
Gemcitabine combined with Apatinib and Toripalimab
Subjects receive Apatinib for oral administration, 250mg, once a day, gemcitabine 1000mg/m2 (Day 1 and Day 8) and Toripalimab , 240mg, (Day 1) of each 21days for at most 6 cycles, followed by Toripalimab 240mg every three weeks (Q3W) and Apatinib 250mg once a day maintenance for the remainder of the study or until documented PD.
Intervention: Gemcitabine combined with Aptinib and Toripalimab
Outcomes
Primary Outcomes
Adverse events
Time Frame: 12months
The safety 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.
Secondary Outcomes
- The proportion of patients who achieved disease control,(12months)
- The proportion of patients who achieved clinical benefit(12 months)
- The proportion of patients who achieved an objective response(12 months)
- Duration of response(12 months)
- Progression-free survival (median and at 6 and 12 months)(12 months)