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Study of Apatinib and MASCT in Patients With Advanced Solid Tumors

9 augusti 2016 uppdaterad av: The First People's Hospital of Lianyungang

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.

Studieöversikt

Detaljerad beskrivning

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.

Studietyp

Interventionell

Inskrivning (Förväntat)

60

Fas

  • Fas 2
  • Fas 1

Kontakter och platser

Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.

Studiekontakt

Studieorter

    • Jiangsu
      • Lianyungang, Jiangsu, Kina, 222000
        • The First's People Hospital of Lianyungang
        • Kontakt:

Deltagandekriterier

Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.

Urvalskriterier

Åldrar som är berättigade till studier

18 år till 80 år (Vuxen, Äldre vuxen)

Tar emot friska volontärer

Nej

Kön som är behöriga för studier

Allt

Beskrivning

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.

Studieplan

Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.

Hur är studien utformad?

Designdetaljer

  • Primärt syfte: Behandling
  • Tilldelning: N/A
  • Interventionsmodell: Enskild gruppuppgift
  • Maskning: Ingen (Open Label)

Vapen och interventioner

Deltagargrupp / Arm
Intervention / Behandling
Experimentell: Apatinib+MASCT
Apatinib+Multiple Antigens Specific Cellular Therapy(MASCT) in patients with advanced solid tumors,excluding T cell lymphoma
Apatinib 850 mg p.o. qd every 28 days until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends
Andra namn:
  • YN968D1
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
Andra namn:
  • Multiple Antigens Specific Cellular Therapy

Vad mäter studien?

Primära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Incidence of treatment-related adverse events
Tidsram: up to 2 years
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

Sekundära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Disease Control Rate (DCR)
Tidsram: upp till 2 år
Sjukdomskontrollfrekvens definieras som antalet patienter med bästa totala svar av fullständig respons (CR), partiell respons (PR) eller stabil sjukdom (SD) baserat på RESIST v1.1-kriterier.
upp till 2 år
Progression-Free Survival (PFS)
Tidsram: From enrollment to progression of disease. Estimated about 6 months.
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)
Tidsram: From enrollment to death of patients. Estimated about 1 year.
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)
Tidsram: up to 2 years
clinical response of treatment according to RESIST v1.1 criteria (ORR, objective response rate)
up to 2 years

Samarbetspartners och utredare

Det är här du hittar personer och organisationer som är involverade i denna studie.

Studieavstämningsdatum

Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.

Studera stora datum

Studiestart

1 juli 2016

Primärt slutförande (Förväntat)

1 juli 2018

Avslutad studie (Förväntat)

1 juli 2018

Studieregistreringsdatum

Först inskickad

20 juli 2016

Först inskickad som uppfyllde QC-kriterierna

25 juli 2016

Första postat (Uppskatta)

26 juli 2016

Uppdateringar av studier

Senaste uppdatering publicerad (Uppskatta)

11 augusti 2016

Senaste inskickade uppdateringen som uppfyllde QC-kriterierna

9 augusti 2016

Senast verifierad

1 juli 2016

Mer information

Termer relaterade till denna studie

Plan för individuella deltagardata (IPD)

Planerar du att dela individuella deltagardata (IPD)?

OBESLUTSAM

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Kliniska prövningar på Avancerade solida tumörer

Kliniska prövningar på Apatinib

3
Prenumerera