Clinical trial NCT04606108: Study of Camrelizumab in Combination With Neoadjuvant Chemotherapy in the Treatment of High-risk Soft Tissue Sarcoma
Official title: A Phase Ⅱ ,Open-label ,Single Institution Study to Investigate the Efficacy and Safety of Camrelizumab in Combination With Neoadjuvant Chemotherapy in the Treatment of High-risk Soft Tissue Sarcoma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Soft Tissue Sarcoma
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
Collaborators: name: Jiangsu HengRui Medicine Co., Ltd.
First posted: 2020-10-28
Enrollment: 62
Sex: ALL
Minimum age (years): 14
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is a open-lable , single arm，single center, phase II clinical study. Target population is patients with high-risk Soft tissue sarcoma. Study objective is to compare the efficacy and safety of camrelizumab in combination with Liposome doxorubicin and Ifosfamide in study population in China. Camrelizumab is a humanized anti-PD1 IgG4 monoclonal antibody.

Detailed description: In this study, eligible subject will be enrolled into study arm to accept study treatment. Treatment cycles of chemotherapy will be at most 8 cycles which will be decided by investigators. Objective response rate will be the primary outcome measures.

Eligibility criteria: Inclusion Criteria:

1. Age 14 to 65 year old;
2. Eastern Cooperative Oncology Group performance status 0-1;
3. The high-risk soft tissue sarcoma of limbs or trunk (FNCLCC grade 3 or FNCLCC grade2 but imaging evaluation showed that it was more than 50% necrosis; more than 5cm; deep tumor), including synovial sarcoma, undifferentiated pleomorphic sarcoma / malignant fibrous histiocytoma, pleomorphic rhabdomyosarcoma, round cell /Myxiod liposarcoma，Malignant peripheral nerve sheath tumors, etc;
4. Patients with soft tissue sarcoma who are ready for neoadjuvant chemotherapy need to meet the following conditions:

   1. According to the evaluation, the patients who received neoadjuvant chemotherapy can achieve standard resection of tumor
   2. If important structures (blood vessels and nerves) are involved, radical operation cannot be performed
5. Having measurable lesion according to RECIST 1.1
6. Life expectancy \>3 months
7. Patients must have adequate organ function
8. Fertile men and women of childbearing potential must agree to use an effective method of birth control from providing signed consent and for 120 days after last study drug administration. Women of childbearing potential must have a negative pregnancy test ≤ 72 hours prior to Day 1 of study
9. Voluntary informed consent , joining the study with good compliance

Exclusion Criteria:

* 1. pregnant or lactating women 2. Known history of hypersensitivity to any components of the camrelizumab formulation, or other antibody formulation.

  3. Active central nervous system (CNS) metastases with clinical symptoms , including cerebral edema, steroid requirement, or progressive disease.

  4. Patients with other malignant tumor within 5 years , except cured skin basal cell carcinoma, cervical carcinoma and Papillary carcinoma of thyroid.

  5. Clinically significant cardiovascular diseases 6. Have received any of the following treatments：
  1. Patients have had prior treatment with PD-1/PD-L1 or CTLA-4 antagonists.
  2. Received any study drug within 4 weeks prior to the first study drug administration.
  3. Enroll in another clinical study, unless it is an observational (non-interventional) clinical study or an intervention follow-up study.
  4. Concurrent medical condition requiring the use of immunosuppressive medications, or immunosuppressive doses of systemic or absorbable topical corticosteroids.
  5. Doses \> 10 mg/day prednisone or equivalent are prohibited within 2 weeks before study drug administration. Note: corticosteroids used for the allergy and nausea, vomiting are allowed. Inhaled or topical use of steroids and adrenocorticosteroid replacement in doses greater than 10mg/ day is permitted in the absence of active autoimmune disease.
  6. Patients who have received a live vaccine within 30 days prior to the first study drug administration.
  7. Major surgery or major trauma within 4 weeks of first study drug administration. Left ventricular ejection fraction (LVEF) is more than 60% .

     7. Severe infection occurred within 4 weeks before the first study drug administration (CTC AE \> grade 2) 8. 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. Stable dose of insulin for type 1 diabetes.

     9. History of immunodeficiency including seropositivity for human immunodeficiency virus (HIV), or other acquired or congenital immune-deficient disease, or organ transplantation and bone marrow transplantation.

     10. Objective evidence of previous or current pulmonary fibrosis history, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonia, pulmonary function damaged seriously etc.

     11. History of active pulmonary tuberculosis infection, or with a history of active pulmonary tuberculosis infection within 1 year prior to enrollment, or with a history of active pulmonary tuberculosis infection prior to 1 year but without formal treatment.

     12. Active hepatitis (transaminase does not meet the inclusion, hepatitis B virus (HBV) DNA ≥10⁴ /ml or hepatitis C virus (HCV) RNA≥103 /ml or higher); Chronic hepatitis B virus carriers who HBV DNA\<2000 IU/ml(\<104/ml), must receive anti-viral treatment throughout the study.

     13. Known history of psychotropic substance abuse, alcohol abuse and drug abuse.

     14. The investigators did not think the participants were suitable for inclusion.

Primary outcomes:
measure: Objective response rate
timeFrame: 24 months
Secondary outcomes:
measure: 2 years Overall Survival (OS) rate
timeFrame: 24 months
measure: 2 years Progression-free survival (PFS) rate
timeFrame: 24 months
measure: Adverse Events (AEs)
timeFrame: 24 months
Other outcomes:
Locations:
city: GuangZhou
country: China
facility: Sun Yat-sen University cancer center
state: Guangdong
Study officials:
References: