Camrelizumab /Apatinib for Recurrent Platinum-resistant Ovarian Cancer

Recurrent Platinum-resistant Ovarian Cancer Clinical Trial

Official title:

Camrelizumab Combined With Apatinib for Recurrent Platinum-resistant Ovarian Cancer: a Phase 2 Single-arm Prospective Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04068974
• Other study ID #: OBU-OvaC-IIT-SHR1210-APA
• Status: Recruiting
• Phase: Phase 2
• Start date: October 28, 2019
• Est. completion date: June 30, 2022

Study information

• Verified date: March 2021
• Source: Peking Union Medical College Hospital
• Contact: Pan Lingya
• Phone: 010-69156204
• Email: Panly[@]pumch.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is intend to improve the progression-free survial of the recurrent paltinum-resistant ovarian cancer. All the participants will receive camrelizumab combined with apatinib.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 28
• Est. completion date: June 30, 2022
• Est. primary completion date: June 30, 2021
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Patients with recurrent -resistant epithelial ovarian cancer, fallopian tube cancer and primary peritoneal cancer previously received twice or more platinum chemotherapy before enrolment;

2. Recurrence occurred within 6 months after the last platinum-containing chemotherapy and had experienced at least one platinum-sensitive recurrent in the past.;

3. Aged 18-70 years;

4. An Eastern Cooperative Oncology Group performance status of 0-2;

5. According to the solid tumor efficacy evaluation standard (RECIST1.1) or i RECIST, at least one measurable lesion, with maximum diameter > 1 cm and lymph node metastasis > 1.5 cm, and the target lesion is not suitable for surgical treatment; the target lesion has not received radiotherapy or recurred in the field of radiotherapy.

6. Expected survival = 4 months;

7. The function of vital organs meets the following requirements: Hemoglobin=80g/L; Absolute neutrophil count=1.5*109/L;Platelets=100 *109/L; Creatinine=1.5 times ULN; Urea nitrogen=2.5 times ULN; Total Bilirubin=ULN; ALT and AST = 2.5 times ULN; Albumin=25g/L; TSH=ULN(if TSH is abnormal, normal T3 and T4 also can acceptable)

8. The subject should be aware of the purpose of the study and the operations required by the study and volunteer to participate in the study before sign the informed consent form.

Exclusion Criteria:

1. Primary platinum refractory patients (first platinum-containing chemotherapy with recurrence within 6 months)

2. Previously exposed to other anti-angiogenic small-molecule TKI drugs, such as pazopanib, sorafenib, regorafenib, cilnitraz, etc. or anti-angiogenic mAbs such as bevacizumab ; or had used an anti-PD-1 antibody, an anti-CTLA-4 antibody, TCR-T, CAR-T and other immune therapy; or 4 weeks before the first administration participated in any other clinical trials of anticancer drugs; or before the first dose Live attenuated vaccines are accepted within 4 weeks or during the study period.

3. Target lesions observed received radiotherapy

4. Other malignant tumors have occurred in the past 3 years..

5. Immunosuppressive drugs used within 14 days prior to the first use of SHR-1210, excluding nasal and inhaled corticosteroids or physiological doses of systemic steroid hormones (ie, no more than 10 mg/day of turmeric or equivalent drug physiological dose) Other corticosteroids).

6. Late-stage patients with symptomatic, disseminated to visceral, short-term risk of life-threatening complications (including uncontrolled large amounts of exudate [thoracic, pericardium, abdominal cavity], pulmonary lymphangitis, and more than 30% liver involvement patients).

7. Any active autoimmune diseases or a history of autoimmune diseases (including but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis, nephritis, hyperthyroidism, decreased thyroid function; subjects with vitiligo or complete remission asthma in childhood and without any intervention, all above can be included; asthma requiring medical intervention for bronchodilators should be excluded). 8 Metastatic foci of the central nervous system have significant symptoms, such as headache, cerebral edema and blurred vision 9. CT or MRI showed tumor lesion 5mm away from the great blood vessel, or tumor invading the local great blood vessel, or accompanied by tumor thrombus formation of the great vein (inferior vena cava of iliac vessel, superior vena cava of pulmonary static vein) 10. Uncontrollable hypertension (systolic blood pressure =140 mmHg or diastolic blood pressure =90 mmHg, despite with the optimal medical treatment.

11. Grade II or higher myocardial ischemia, myocardial infarction or poor control arrhythmia (including male with QTc interval = 450ms, or female with QTc interval= 470ms). According to NYHA criteria, grade III to IV cardiac insufficiency, or cardiac color Doppler ultrasound examination showed left ventricular ejection fraction (LVEF) <50%; myocardial infarction occurred within 6 months before enrollment, New York Heart Association Level II or above failure, uncontrolled angina, uncontrolled severe ventricular arrhythmia, pericardial disease with clinically significant, or electrocardiogram suggesting acute ischemia or abnormal active conduction system. 12, Abnormal coagulation (INR > 1.5 or prothrombin time (PT) > ULN + 4 seconds or APTT > 1.5ULN), with bleeding tendency or undergoing thrombolysis or anticoagulant therapy.

13. Half of a teaspoons (2.5 ml) or more hemoptysis was found within the first 2 months or there were significant clinical bleeding symptoms or clearly propensity bleeding within 3 months before participant in the study, such as gastrointestinal bleeding, hemorrhagic gastric ulcer, fecal occult blood ++ or above in baseline or vasculitis; artery or venous thrombosis events within 6 months prior to the study, such as cerebrovascular accidents (Including transient ischemic attacks, cerebral hemorrhage, cerebral infarction, deep vein thrombosis and pulmonary embolism.

14. Severe infections within 4 weeks prior to accept medication (eg, intravenous infusion of antibiotics, antifungal or antiviral drugs), or unexplained fever during screening/first administration >38.5 °C 15. Those who have a history of psychotropic drug abuse and are unable to quit or have mental disorders.

16. Major surgical procedures were performed within 4 weeks before the first administration. Or open wounds or fractures.

17. There are obvious factors affecting oral drug absorption, such as inability to swallow, chronic diarrhea and intestinal obstruction. Or sinus or perforation of empty organs within 6 months.

18. Routine urine test indicated that urinary protein (++) or more, confirmed urinary protein (>1.0 g) within 24 hours.

19. Patients with a history of allergy may be potentially allergic or intolerant to Apatinib and biological agents SHR-1210.

20. Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS), active hepatitis B (HBV DNA (> 500 IU/ml), hepatitis C (hepatitis C antibody positive, and HCV-RNA higher than the lower limit of the analysis method) or co-infection with hepatitis B and hepatitis C.

21. There is any situation that may damage the subject or cause the subject to fail to meet or implement the research requirements.

Related Conditions & MeSH terms

• Carcinoma, Ovarian Epithelial
• Ovarian Neoplasms
• Recurrent Platinum-resistant Ovarian Cancer

Intervention

Drug:
• Camrelizumab (SHR-1210)
Anticancer T-cell activity is regulated by multiple suppressive mechanisms, including tumour-expressed programmed cell death ligand 1 (PD-L1) signalling to the T-cell inhibitory receptor (programmed death protein 1 [PD-1]). Monoclonal antibodies like SHR-1210 that can block this pathway.
• Apatinib
Apatinib is an oral small-molecule tyrosine kinase inhibitor that selectively binds to and inhibits VEGF receptor 2.

Locations

Country	Name	City	State
China	Peking Union Medical College Hospital	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Peking Union Medical College Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate	The proportion of participants with tumor size reduction of a predefined amount and for a minimum time period.	Up to two years
Secondary	Progression Free Survival	The time from treatment until objective tumor progression or death, whichever occurs first.	Up to two years
Secondary	Disease Control Rate	The proportion of patients with complete response, partial response or keep stable diease after accept treatment.	Up to two years
Secondary	Duration of Response (DoR)	The time from firstly complete response or partly response to progressive disease.	Up to two years
Secondary	Assessment of safety	The quantity and degree of adverse event and serious adverse event from	Up to two years