Famitinib Plus Anti-PD1 Therapy for Advanced Urinary System Tumor, Advanced Gynecological Tumors

Sponsor

Jiangsu HengRui Medicine Co., Ltd. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT03827837

Collaborator

(none)

265

Enrollment

Location

Arm

46.3

Anticipated Duration (Months)

5.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Phase II multi-chort, adaptive two-stage, open label, nonrandomized study. The aim of our study is to evaluate the efficacy and safety of anti-PD-1 antibody SHR-1210(Camrelizumab) in combination with a small-molecule multikinase inhibitor Famitinib in subjects with advanced RCC/UC/CC/EC and recurrent OC.

chort1: Renal Cell Carcinoma (RCC) chort2: Urothelial Carcinoma(UC) chort3: Ovarian Cancer (OC) chort4: Cervical Cancer (CC) chort5: Endometrial Cancer (EC)

Condition or Disease	Intervention/Treatment	Phase
Renal Cell Carcinoma Urothelial Carcinoma Cervical Cancer Ovarian Cancer Recurrent Endometrial Cancer	Biological: SHR-1210 Drug: Famitinib	Phase 2

Detailed Description

Stage 1: Approximately 110 participants will be recruited, 22 participants per chort; Stage 2: Approximately 55 participants will be recruited, 11 participants per chort, if more than 7（including 7） patients reached ORR in every chort ; Approximately 155 participants will be recruited, 21 participants per chort, if 3 ≤ patients <7 patients reached ORR in every chort.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

265 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Famitinib Malate Plus Anti-PD1 Therapy (SHR-1210) in Advanced Renal Cell Carcinoma, Urothelial Carcinoma, Advanced Cervical Cancer, Relapse Ovarian Cancer, Endometrial Cancer: Multi-institutional, Open-label, Phase 2 Trial

Actual Study Start Date :

Jan 23, 2019

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

Dec 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: SHR-1210 combined with Famitinb SHR-1210 + Famitinib	Biological: SHR-1210 SHR-1210 is a humanized anti-PD1 IgG4 monoclonal antibody Other Names: Camrelizumab Drug: Famitinib a small-molecule multikinase inhibitor Other Names: Famitinib Malate Capsule

Arm

Intervention/Treatment

Experimental: SHR-1210 combined with Famitinb

SHR-1210 + Famitinib

Biological: SHR-1210

SHR-1210 is a humanized anti-PD1 IgG4 monoclonal antibody

Other Names:

Camrelizumab

Drug: Famitinib

a small-molecule multikinase inhibitor

Other Names:

Famitinib Malate Capsule

Outcome Measures

Primary Outcome Measures

Overall response rate (ORR) [Up to 2 years]
Defined as complete or partial response per RECIST 1.1 criteria with assessment every 9 weeks

Secondary Outcome Measures

Duration of Response (DoR) [Up to 2 years]
Duration of Response (DoR) per RECIST 1.1
Disease Control Rate (DCR) [Up to 2 years]
Disease Control Rate per RECIST 1.1
Time to objective response(TTR) [Up to 2 years]
Time to objective response per RECIST 1.1
Progression-free survival(PFS) [Up to 2 years]
Progression-free survival(PFS) per RECIST 1.1
Overall survival(OS) [Up to 2 years]
Overal Survial will be calculated based on Kaplan-Meier estimates
12-month survival rate [Up to 1 year]
12-month survival rate will be calculated based on Kaplan-Meier estimates of Overall survival at 12 months
number of participants who experience an adverse event (AE) [From the first assignment of informed consent form up to 90 days after the last dose]
number of participants who experience an adverse event (AE) per CTCAE 4.03
serum SHR-1210 concentrations [From the first dose up to 30 days after the last dose]
serum SHR-1210 concentrations
Positive rate of ADA [From the first dose up to 30 days after the last dose]
Positive rate of anti-SHR1210 antibody
Maximum Observed Plasma Concentration (Cmax) [Day 1 of cycle 3 (each cycle is 21 days)]
Cmax, based PK parameters
Time to Reach Maximum Observed Plasma Concentration (Tmax) [Day 1 of cycle 3 (each cycle is 21 days)]
Summarized by dose, cycle, day and time
Apparent Oral Clearance (CL/F) [Day 1 of cycle 3 (each cycle is 21 days)]
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Be willing and able to provide written informed consent/ for the trial.
Be at least 18 years of age on day of signing informed consent, male or female.
Patients with one of the following tumors:

Histologically or cytologically confirmed diagnosis of advanced renal cell carcinoma (defined as more than 50% clear cell component) after failure of IL-2 and/or anti-VEGF TKI treatment. If patients didn't want to use anti-VEGF TKI medicine or couldn't stand anti-VEGF TKI medicine costs, they will also be considered.
Histologically or cytologically confirmed diagnosis of unresectable urothelial carcinoma of the renal pelvis, ureter, bladder, or urethra (defined as more than 50% transitional cell component) after failure of no more than two prior platinum-based chemotherapeutic regimen.
Histologically or cytologically confirmed diagnosis of advanced squamous cell carcinoma of the cervix after failure of first-line system treatment.
Histologically confirmed diagnosis of recurrent or refractory epithelial ovarian cancer, fallopian tube cancer or primary peritoneal cancer that are relapsed and resistant (recurred less than 6 months after chemotherapy) or refractory (progressed on chemotherapy) to prior platinum-based standard care systemic regimen.
Histologically confirmed diagnosis of recurrent or refractory endometrial cancer that are relapsed and resistant or refractory (progressed on chemotherapy) to prior platinum-based standard care systemic regimen.

At least one measurable lesion according to RECIST 1.1.
The patients can swallow pills.
Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1.
Life expectancy of at least 12 weeks.
The results of patients' blood tests are as follows:-Neutrophils≥1.5E+9/L; - Plt≥90E+9/L; -Hb≥90g/L; -ALB≥30g/L ;-TSH≤1×ULN;-TBIL ≤ 1 ×ULN;-ALT and AST ≤ 3 ×ULN; AKP≤ 2.5×ULN; -Creatinine ≤ 1.5×ULN.
Male or Female patient of childbearing potential (entering the study after a menstrual period and who have a negative pregnancy test), who agrees to use two methods (one for the patient and one for the partner) of medically acceptable forms of contraception during the study and for 3 months after the last treatment intake.

Exclusion Criteria:

Patients with any active autoimmune disease or history of autoimmune disease, including but not limited to the following: hepatitis, pneumonitis, uveitis, colitis (inflammatory bowel disease), hypophysitis, vasculitis, nephritis, hyperthyroidism, and hypothyroidism, except for subjects with vitiligo or resolved childhood asthma/atopy. Asthma that requires intermittent use of bronchodilators or other medical intervention should also be excluded.
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.
Known history of hypersensitivity to other antibody formulation.
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 2 weeks prior to trial treatment.
Hypertension and unable to be controlled within normal level following treatment of anti-hypertension agents: systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥ 90 mmHg.
Clinically significant cardiovascular and cerebrovascular diseases, including but not limited to（1）Congestive heart failure (New York heart association (NYHA) class > 2)；（2）unstable or severe angina; （3）myocardial infarction within 12 months before enrollment；（4） ventricular arrhythmia which need medical intervention.（5）QTc>450ms（male）/QTc>470ms (female)；
Coagulation abnormalities (INR>2.0、PT>16s), with bleeding tendency or are receiving thrombolytic or anticoagulant therapy.
Bleeding history, having bleeding event（≥3 Grade according CTCAE 4.0 ）within 4 weeks before screening.
Tumor invasion around major vessels shown by imaging, high risk of major vascular invasion leading to massive hemorrhage judged by investigators.
Previous Arterial/venous thrombosis events within 6 months.
Known hereditary or acquired bleeding and thrombosis tendency.
Proteinuria ≥ (++) and 24 hours total urine protein > 1.0 g.
Prior chemotherapy, radiotherapy, surgery therapy within 4 weeks or palliative radiotherapy within 2 weeks or target therapy within 5 half-life of the drug before the study drug administration, or any unresolved AEs > Common Terminology Criteria for Adverse Events (CTCAE) Grade 1.
Active infection or an unexplained fever > 38.5°C within 7 days before the study drug administration, or baseline WBC>15×E+9/L .
Has known history of Interstitial lung disease, or using steroids evidence of active, non-infectious pneumonitis, or would interfere with the detection and handling of suspicious drug-related pulmonary toxicity.
History of immunodeficiency or human immunodeficiency virus (HIV) infection.
HBV DNA>500 IU/ml，HCV RNA>1000copies/ml，HBsAg+ and anti-HCV+；
Has a known additional malignancy within the last 5 years, or that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer or patients with recurrent ovarian cancer has a known additional breast cancer that has been radical mastectomy and doesn't relapse within 3 years.
Patients with treatment history of SHR-1210 or any other PD-L1 or PD-1 antagonists or famitinib.
Patients who may receive live vaccine during the study, or previous had vaccination within 4 weeks.
Any other medical, psychiatric, or social condition deemed by the investigator to be likely to interfere with a subject's safety and participate in the study or would interfere with the interpretation of the results or lead to the trial being terminated early.