Brief Title
Famitinib Plus Anti-PD1 Therapy for Advanced Urinary System Tumor, Advanced Gynecological Tumors
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
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)
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 Phase
Phase 2
Study Type
Interventional
Primary Outcome
Overall response rate (ORR)
Secondary Outcome
Duration of Response (DoR)
Condition
Renal Cell Carcinoma
Intervention
SHR-1210
Study Arms / Comparison Groups
SHR-1210 combined with Famitinb
Description: SHR-1210 + Famitinib
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
Biological
Estimated Enrollment
265
Start Date
January 23, 2019
Completion Date
June 2021
Primary Completion Date
June 2020
Eligibility Criteria
Inclusion Criteria:
1. Be willing and able to provide written informed consent/ for the trial.
2. Be at least 18 years of age on day of signing informed consent, male or female.
3. 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.
4. At least one measurable lesion according to RECIST 1.1.
5. The patients can swallow pills.
6. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1.
7. Life expectancy of at least 12 weeks.
8. 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.
9. 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:
1. 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.
2. 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.
3. Known history of hypersensitivity to other antibody formulation.
4. 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.
5. 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.
6. 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)；
7. Coagulation abnormalities (INR>2.0、PT>16s), with bleeding tendency or are receiving
thrombolytic or anticoagulant therapy.
8. Bleeding history, having bleeding event（≥3 Grade according CTCAE 4.0 ）within 4 weeks
before screening.
9. Tumor invasion around major vessels shown by imaging, high risk of major vascular
invasion leading to massive hemorrhage judged by investigators.
10. Previous Arterial/venous thrombosis events within 6 months.
11. Known hereditary or acquired bleeding and thrombosis tendency.
12. Proteinuria ≥ (++) and 24 hours total urine protein > 1.0 g.
13. 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.
14. Active infection or an unexplained fever > 38.5°C within 7 days before the study drug
administration, or baseline WBC>15×E+9/L .
15. 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.
16. History of immunodeficiency or human immunodeficiency virus (HIV) infection.
17. HBV DNA>500 IU/ml，HCV RNA>1000copies/ml，HBsAg+ and anti-HCV+；
18. 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.
19. Patients with treatment history of SHR-1210 or any other PD-L1 or PD-1 antagonists or
famitinib.
20. Patients who may receive live vaccine during the study, or previous had vaccination
within 4 weeks.
21. 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.
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Dingwei Ye, MD, (+86) 021-50118402, [email protected]
Location Countries
China
Location Countries
China
Administrative Informations
NCT ID
NCT03827837
Organization ID
SHR-1210-II-213
Responsible Party
Sponsor
Study Sponsor
Jiangsu HengRui Medicine Co., Ltd.
Study Sponsor
Dingwei Ye, MD, Principal Investigator, Fudan University
Verification Date
January 2019