Study of Apatinib and MASCT in Patients With Advanced Solid Tumors

Phase I/IIa, Single-Arm, Open Study of Apatinib and MASCT in Patients With Advanced Solid Tumors

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

Study Overview

• Status: Unknown
• Conditions: Advanced Solid Tumors; Excluding T Cell Lymphoma
• Intervention / Treatment: Drug: Apatinib; Biological: MASCT

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.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Lianyungang, Jiangsu, China, 222000
      • The First's People Hospital of Lianyungang

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Apatinib+MASCT; Apatinib+Multiple Antigens Specific Cellular Therapy(MASCT) in patients with advanced solid tumors,excluding T cell lymphoma

Drug: Apatinib; Apatinib 850 mg p.o. qd every 28 days until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends; Other Names: YN968D1; Biological: MASCT; Dendritic cells(DC) loaded with 17 antigens ih day 8, cytotoxic T lymphocytes ( CTL) induced by DC IV day 21-28, every 28 days until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends; Other Names: Multiple Antigens Specific Cellular Therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of treatment-related adverse events	The incidence of treatment-related adverse events were graded with the use of the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0.	up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Control Rate (DCR)	Disease control rate is defined as the number of patients with a best overall response of complete response (CR), partial response (PR), or stable disease (SD) based on RESIST v1.1 criteria.	up to 2 years
Progression-Free Survival (PFS)	The length of time from enrollment until the time of progression of disease (PFS, progression-free survival)	From enrollment to progression of disease. Estimated about 6 months.
Overall Survival (OS)	The length of time from enrollment until the time of death (OS, overall survival)	From enrollment to death of patients. Estimated about 1 year.
Objective Response Rate (ORR)	clinical response of treatment according to RESIST v1.1 criteria (ORR, objective response rate)	up to 2 years

Collaborators and Investigators

• Sponsor: The First People's Hospital of Lianyungang
• Collaborators: Hengrui Yuanzheng Bio-Technology Co., Ltd.

Study record dates

Study Major Dates

• Study Start: July 1, 2016
• Primary Completion (Anticipated): July 1, 2018
• Study Completion (Anticipated): July 1, 2018

Study Registration Dates

• First Submitted: July 20, 2016
• First Submitted That Met QC Criteria: July 25, 2016
• First Posted (Estimate): July 26, 2016

Study Record Updates

• Last Update Posted (Estimate): August 11, 2016
• Last Update Submitted That Met QC Criteria: August 9, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, T-Cell; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Apatinib
• Other Study ID Numbers: AM-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED