Clinical trial NCT04074564: MASCT-I Combined With Apatinib and/or Camrelizumab in the Treatment of Bone and Soft Tissue Sarcoma
Official title: An Exploratory Study Evaluating the Safety and Efficacy of MASCT-I Combined With Apatinib Mesylate and/or Camrelizumab in the Treatment of Patients With Advanced Bone and Soft Tissue Sarcoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Sarcoma
Keywords: MASCT-I
Cell-based immunotherapy
Camrelizumab
Apatinib
Tumor associated antigen
Lead sponsor: HRYZ Biotech Co.
Sponsor class: INDUSTRY
First posted: 2019-08-30
Enrollment: 60
Sex: ALL
Minimum age (years): 14
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will evaluate the safety and preliminary efficacy of Multi-Antigen Stimulated Cell Therapy-I Injection (MASCT-I) in combination with Apatinib and/or Camrelizumab in patients with advanced bone and soft-tissue sarcoma.

Detailed description: This is a single-center, open-label, exploratory study to evaluate the safety, preliminary efficacy and immune response of MASCT-I with Apatinib and/or Camrelizumab in the treatment of patients with advanced bone and soft-tissue sarcoma. 60 patients with advanced bone and soft-tissue sarcoma will be recruited.

This study include two parts. In part A, patients were randomized into two groups: one group received MASCT-I A+Camrelizumab+Apatinib, and the other group received MASCT-I B +Camrelizumab+Apatinib, the administration schedules for MASCT-I is different between two groups. A total of 20 patients were planned to be recruited in part A. In part B, patients will be treated with MASCT-I (based on the administration schedule selected from part A) in combination with Apatinib. 40 patients were planned to be recruited in part B.

MASCT-I A and MASCT-I B were administered mainly at different frequencies.

Eligibility criteria: Inclusion Criteria:

1. Aged 14-70 years old.
2. Obtain the written informed consent of the patient/legal representative;
3. In patients with unresectable recurrent or metastatic advanced bone and soft tissue sarcoma, histologically or cytologically confirmed objective radiographic progression (RECIST 1.1) after first-line or further lines treatment, and the maximum diameter of metastatic lesions is ≤ 8 cm. When objective radiographic progression (RECIST 1.1) found in patients with alveolar soft-part sarcoma and clear cell sarcoma, even if they have not received first line or further lines treatment could also be included in this study;
4. The interval between the last PD-1/PD-L1/CTLA-4 antibody treatment and enrollment was more than 4 weeks;
5. At least one measurable and assessable lesion defined by RECIST 1.1;
6. ECOG performance status of 0-1 (2 for amputees);
7. Estimated life expectancy ≥ 6 months;
8. At least 4 weeks after the last chemotherapy;
9. Cardiopulmonary function is basically normal.
10. Tumor tissue specimens could be provided for PDL1, MSI detection.
11. Blood samples could be provided for immune response test.
12. Patients with potential fertility need to use a medically approved contraceptive measure (such as intrauterine device, contraceptive pill or condom) during the study treatment period and within 6 months after the end of the study treatment period; The serum or urine HCG test must be negative within 72 hours before the study was included; And must be non lactating.
13. Patients with organ function as defined below (any blood components and growth factors are not allowed within 14 days before screening):

A) Hemoglobin ≥ 90g/L;

B) Leukocyte ≥3.0 \*109/L;

C) The absolute neutrophil count (ANC) ≥ 1.5 x 109/L;

D) Platelet ≥ 70 \*109/L;

E) ALT, AST ≤ 2.5 ULN (Upper Limit of Normal);

F) ALP ≤ 2.5 ULN;

G) Serum total bilirubin \< 1.5 ULN; Patients with Gilbert's syndromes (persistent or repeated hyperbilirubinemia \[mainly unconjugated bilirubin\], in the absence of evidence of hemolysis or liver disease), are allowed to consult a doctor.

H) Serum urea nitrogen and creatinine ≤ 1.5 ULN;

I) Serum albumin ≥30g/L.

Exclusion Criteria:

1. Subjects have participated in another clinical study at the same time, observational studies are not included.
2. Those who have received other systemic anti-tumor treatment.
3. Pregnant or plan to get pregnant.
4. Allergic to sodium citrate or human albumin.
5. Those with brain metastases ( Brain metastases confirmed by imaging, inactive, asymptomatic, whether or not treated, and stable for more than 6 months can be included);
6. Subjects have received MASCT or other cellular immunotherapy in the past 1 year.
7. Subjects with severe coagulation dysfunction (PT, TT, APTT or fibrinogen was found to be abnormal and have clinical significance).
8. Subjects have undergone significant bleeding symptoms or bleeding tendency within 3 months before enrollment, or have undergone arterial/venous thrombotic events within 6 months before enrollment. Subjects with long-term anticoagulation of warfarin or heparin or long-term antiplatelet therapy (aspirin ≥300mg/ day or clopidogrel ≥75mg/ day) are not included in this study.
9. Allogeneic organ transplanters, including bone marrow transplantation and peripheral stem-cell transplantation, corneal transplantation is not included.
10. Subjects were using immunosuppressive agents or systemic or absorbable local hormones to achieve immunosuppressive purposes (dose \> 10mg/day of prednisone or other therapeutic hormones) and were still using them within 2 weeks before enrollment.
11. Systematic or long-term use of immunomodulators such as interferon, thymosin and immunosuppressive drugs such as adrenocorticosteroids in half a year; Systematic or long-term use of immunomodulators for more than three months and immunosuppressive drugs for more than one month;
12. Subjects have any active autoimmune disease or history of autoimmune disease.
13. Subjects with active tuberculosis.
14. Subjects who have undergone major surgery within 28 days before 1st treatment (according to the investigator's definition);
15. Subjects were infected with hepatitis B virus, hepatitis C virus or HIV, or syphilis.
16. Subjects with or have history of peripheral nervous system disorders or mental disorders.
17. Subjects have active infection or fever of unknown cause during screening and before 1st treatment more than 38.5 degrees (patients with fever caused by cancer is eligible for enrollment according to investigator's judgement);
18. Chronic systemic diseases such as severe liver disease (such as cirrhosis, etc.), kidney disease, respiratory disease, or diabetes mellitus (fasting plasma glucose \> 7.0mmol/L or 2-hour postprandial plasma glucose \>11.1mmol/L) that cannot be well controlled by medical treatment, hypertension (systolic blood pressure \>140 mmHg or diastolic blood pressure \>90mmHg);
19. Subjects with other malignant tumors (except cured skin basal cell carcinoma, thyroid carcinoma and cervical carcinoma in situ) within 5 years before enrollment or at enrollment;
20. Subjects with poorly controlled cardiac symptoms or diseases, such as: (1) heart failure of NYHA class 2 or higher (2) unstable angina pectoris (3) myocardial infarction within 1 year (4) clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention (5) LVEF\<50% (6) poorly controlled arrhythmias (QTcF interval \> 450ms for men and \> 470ms for women);
21. According to investigator's judgement, those who are not suitable for enrollment.

Primary outcomes:
measure: Adverse events and serious adverse events (safety)
timeFrame: 4 years
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: 4 years
measure: Progression-Free Survival (PFS)
timeFrame: 4 years
measure: Disease Control Rate (DCR)
timeFrame: 4 years
measure: Overall Survival (OS)
timeFrame: 4 years
measure: immune response
timeFrame: 4 years
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Sixth People's Hospital
state: Shanghai
Study officials:
References: