Clinical trial NCT05113355: Chidamide Plus Sintilimab for Chemotherapy-refractory Advanced High-grade Neuroendocrine Neoplasm
Official title: Chidamide and Sintilimab for Chemotherapy-refractory Advanced High-grade Neuroendocrine Neoplasm: a Prospective, Single-arm, Multicenter, Phase 2 Clinical Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Neuroendocrine Tumors
Neuroendocrine Tumor Grade 3
Neuroendocrine Carcinoma
Neuroendocrine Neoplasm
Keywords: Histone Deacetylase Inhibitors
Chidamide
Neuroendocrine Neoplasm
PD-1
Sintilimab
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
Collaborators: name: The First Affiliated Hospital of Xiamen University
name: Harbin Medical University
First posted: 2021-11-09
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to explore the efficacy and safety of chidamide combined with sintilimab in chemotherapy-refractory advanced high-grade neuroendocrine neoplasm.

Detailed description: This study is a single-arm, multi-center, two-stage, phase II clinical trial conducted in China. This study adopts Simon's two-stage design, and the inclusion criteria and exclusion criteria of the two stages were consistent. Six patients with high-grade neuroendocrine neoplasm will be enrolled in the first stage. If more than one complete or partial responses were seen at planned interim analysis, the additional 17 patients will be recruited in the second stage and a total of 23 patients will be treated.

Eligibility criteria: Inclusion Criteria:

1. Age ≥ 18 years;
2. Histologically confirmed advanced and metastatic high-grade neuroendocrine neoplasm;
3. Receive ≤ 2 types of chemotherapy for high-grade neuroendocrine tumors and had tumor progression;
4. ECOG ≤ 2;
5. Have at least one measurable lesion according to RECIST version 1.1;
6. Absolute neutrophil count ≥ 1.5×109 / L, platelet count ≥ 100×109 / L, hemoglobin ≥ 90 g/L;
7. Provide tumor samples for pathological diagnosis and PD-L1 biomarker detection;
8. Have ability to sign a written informed consent.

Exclusion Criteria:

1. Small cell lung cancer;
2. Have surgery or trauma within 4 weeks before enrollment, or are expected to receive surgical treatment;
3. Previous use of HDAC inhibitors;
4. Previous use of PD-1/PD-L1/PD-L2/CTLA-4 inhibitors;
5. Allergy to related drug components;
6. Have a medical history of immune deficiency diseases, or organ transplantation;
7. Have active autoimmune diseases requiring treatment or a medical history of autoimmune diseases in the past 2 years;
8. Have uncontrolled or significant cardiovascular disease;
9. Abnormal liver function (total bilirubin \> 1.5×upper limit of normal); Transaminases (ALT/AST) \>2.5×upper limit of normal (\>5x upper limit of normal for patients with liver metastases), abnormal renal function (serum creatinine \> 1.5×upper limit of normal);
10. Pregnancy ;
11. Receive any live or live attenuated vaccine within 4 weeks before enrollment;
12. Have serious diseases that may endanger the safety of patients, or affect patients to complete the research;
13. Any serious mental or cognitive disorder;
14. Patients are currently enrolled in another drug clinical trial within 4 weeks prior to enrollment;
15. Any other condition which is inappropriate for the study in the opinion of the investigators.

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Up to 2 years
Secondary outcomes:
measure: Disease Control Rate (DCR)
timeFrame: Up to 2 years
measure: Progression-free Survival (PFS)
timeFrame: Time from the date of enrollment to the earliest of documented disease progression or death, assessed up to 2 years
measure: Overall Survival (OS)
timeFrame: Time from the date of enrollment to the earliest of documented death, assessed up to 3 years
measure: Treatment-related Adverse Events (Safety)
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Xiamen
country: China
facility: The First Affiliated Hospital of Xiamen University
state: Fujian
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
state: Heilongjiang
Study officials:
affiliation: Peking Union Medical College Hospital
name: Chunmei Bai, M.D.
role: PRINCIPAL_INVESTIGATOR
References: