Clinical trial NCT02844881: Study of Apatinib and MASCT in Patients With Advanced Solid Tumors
Official title: Phase I/IIa, Single-Arm, Open Study of Apatinib and MASCT in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Advanced Solid Tumors
Excluding T Cell Lymphoma
Lead sponsor: The First People's Hospital of Lianyungang
Sponsor class: OTHER
Collaborators: name: Hengrui Yuanzheng Bio-Technology Co., Ltd.
First posted: 2016-07-26
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The study is aimed to evaluate the efficacy and safety of Apatinib and MASCT in patients with advanced solid tumors.

Detailed description: Angiogenesis is a hallmark of cancer, together with vascular endothelial growth factor (VEGF) as one of the most important angiogenic drivers. Inhibitors targeting the VEGF/VEGFR-pathway have shown beneficial effects in many cancer patients, but they are transient and followed by fast regrowth. Similarly, the effectiveness of tumor immunotherapies has been limited by tumor-mediated escape mechanisms and immune suppression. By combining the two strategies, antiangiogenic immunotherapy offers the possibility to more vigorously inhibit tumor angiogenesis and promote an enduring immune-stimulatory milieu that leads to prolonged survival benefits in cancer patients.

Apatinib is a small-molecule tyrosine kinase inhibitor (TKI) that highly selectively binds to and strongly inhibits vascular endothelial growth factor receptor 2 (VEGFR-2). Apatinib has been demonstrated as monotherapy prolongs OS in patients with gastric or gastroesophageal junction adenocarcinoma after two or more lines of chemotherapy with moderate, reversible, and easily managed adverse events.

Multiple antigens specific cellular therapy (MASCT) is a new immunotherapy that dendritic cells(DC) was induced from autologous peripheral blood. The DC can then be loaded with 17 antigens and re-infused. In vitro, antigen-pulsed DC can stimulate autologous T-cell proliferation and induction of autologous specific cytotoxic T-cells(CTL)，similarly re-infused. The previous research data showed that MASCT had the modest overall response and less adverse effects for Hepatocellular Carcinoma patients.

The study is aimed to evaluate the efficacy and safety of Apatinib and MASCT in patients with advanced solid tumors.

Eligibility criteria: Inclusion Criteria:

1. Patients with histologically-confirmed, advanced (unresectable) solid tumors who have progressed on standard therapy.
2. With written informed consent signed voluntarily by patients themselves.
3. The time of between Patients enrollment and the end of other anti-tumors therapies≤1 month
4. Eastern Cooperative Oncology Group Performance Status (ECOG P.S.) of ≤ 2
5. At least one measurable lesion as defined by RECIST criteria 1.1 for solid tumors.
6. Life expectancy ≥6 months.
7. With normal cardiopulmonary function.
8. Patients have adequate organ function as defined by the following criteria:

   * Hemoglobin (HGB) ≥85g/L
   * Absolute neutrophil count (ANC) ≥1.0×109/L
   * White blood cell (WBC) ≥3.0×109/L
   * Platelet count ≥50×109/L
   * Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) of ≤2.5 upper normal limitation (UNL) or ≤5 UNL in case of liver metastasis
   * Alkaline phosphatase (ALP)≤2.5 UNL
   * Total bilirubin (TBil) of ≤1.5 UNL
   * Blood urea nitrogen (BUN) and Creatinine (Cr) of≤1.5 UNL
   * Albumin (ALB) ≥30g/L

Exclusion Criteria:

1. Pregnant or expecting to pregnant
2. Participated in other clinical trials before screening except of observational study.
3. Known allergic history of sodium citrate drugs.
4. Known history of organ transplant, including autologous bone marrow transplantation and peripheral stem cell transplantation.
5. Known active brain metastases as determined by CT or MRI evaluation.
6. The use of immunosuppressive drugs with current or 14 days before enrollment.
7. Know the period of systemic and continuous use of immunomodulatory agents (such as interferon, thymosin, traditional Chinese medicine) within 6 months.
8. Prior therapy with anti-programmed death-1 (anti-PD-1), anti-programmed cell death ligand 1 (anti-PD-L1), or anti-Cytotoxic T lymphocyte-associated antigen 4 (anti-CTLA-4) antibody (including any other antibody or drug specifically targeting T-cell co-stimulation).
9. Known history of primary immunodeficiency diseases.
10. Known history of tuberculosis.
11. Known active human immunodeficiency virus (HIV), hepatitis B, or hepatitis C.
12. Patients with serious infection, hepatopathy, nephropathy, respiratory disease, cardiovascular disease or incontrollable diabetes, etc.
13. Patients have other malignant tumors within 5 years,excluding melanoma and carcinoma in situ of cervix.
14. Treatment with any anti-tumors agent within 28days of first administration of study treatment.

Primary outcomes:
measure: Incidence of treatment-related adverse events
timeFrame: up to 2 years
Secondary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: From enrollment to progression of disease. Estimated about 6 months.
measure: Overall Survival (OS)
timeFrame: From enrollment to death of patients. Estimated about 1 year.
measure: Objective Response Rate (ORR)
timeFrame: up to 2 years
measure: Disease Control Rate (DCR)
timeFrame: up to 2 years
Other outcomes:
Locations:
city: Lianyungang
country: China
facility: The First's People Hospital of Lianyungang
state: Jiangsu
Study officials:
References: