Th-1 Dendritic Cell Immunotherapy Plus Standard Chemotherapy for Pancreatic Adenocarcinoma

Официальное название

Phase I Study of Th-1 Dendritic Cell Immunotherapy in Combination With Standard Chemotherapy for the Adjuvant Treatment of Pancreatic Adenocarcinoma (DECIST)

Обзор

This is a phase 1, first in human, dose escalation study for safety and feasibility of multi-dose dendritic cell (DC) therapy for pancreatic ductal adenocarcinoma (PDAC) including adenosquamous carcinoma administered after surgical resection of PDAC.

Подробное описание

The primary objective of this phase 1, first in human trial is to determine the safety, toxicity, and feasibility of delivering autologous DCs loaded with pancreatic adenocarcinoma lysate and mRNA to pancreatic cancer patients following surgery.

After having undergone surgical resection of their PDAC (with or without prior neoadjuvant chemotherapy), patients will undergo apheresis for the manufacture of the DC therapy. Once the DC therapy has been manufactured, it will be administered by image-guided injections proximal to a lymph node near the surgical bed with concurrent use of subcutaneous peg-IFN. Patients will have the option to receive additional doses of the DC therapy and peg-IFN if they are eligible and interested.

Вмешательства

• Биопрепарат Autologous DC Therapy
  Autologous DC Therapy

Первичные конечные точки

• Safety of DC Therapy [Срок оценки: From treatment start until 6 weeks after.]
• Number of participants who experienced Dose Limiting Toxicities (DLTs) [Срок оценки: From treatment start until 6 weeks after.]

Вторичные конечные точки (2)

• Recurrence-Free Survival [Срок оценки: From surgery until recurrence or up to 3 years after surgery, whichever comes first.]
• Overall Survival [Срок оценки: From surgery until death or up to 3 years after surgery, whichever comes first.]

Критерии участия

Критерии включения

An individual must meet all of the following criteria:

• Provision of signed and dated informed consent form
• Male or female, aged 18 years and older
• Cytological or pathological confirmation of adenocarcinoma or adenosquamous carcinoma of the pancreas is deemed to be potentially resectable or borderline resectable based on tumor and host factors. This may include patients who undergo upfront resection or those who receive neoadjuvant chemotherapy +/- radiation prior to resection.
• Adequate kidney, liver, bone marrow function, and immune function, as follows, within 28 days prior to registration:

• Hemoglobin ≥ 8.0 gm/dL
• Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3
• Platelet count ≥ 75,000 /mm3
• Total bilirubin ≤ 1.5 times upper limit of normal (ULN),
• Aspartate transaminase AST (SGOT) and alanine aminotransferase ALT (SGPT) ≤ 2.5 times the ULN
• ECOG performance status ≤ 2.
• For women of childbearing potential (WOCBP): use of highly effective contraception must be discussed with participants. NOTE: Patient must agree to start contraception at least 30 days before first vaccination and continue for at least 12 weeks after her last vaccination.
• WOCBP must have a negative serum pregnancy prior to vaccination
• For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner during study participation and for an additional 12 weeks following discontinuations of last vaccination.
• Patient must agree to not donate blood for up to 90 days after last vaccination.

Критерии исключения

An individual who meets any of the following criteria will be excluded from participation in this study:

• Unresectable or metastatic (stage IV) pancreatic cancer.
• Patients with known HIV and a positive viral load.
• Patients with active HBV and HCV infection. Those who are Hepatitis B sAb positive as well as those who are Hepatitis C Ab positive, but Hepatitis C RNA viral load negative will not be excluded.
• Patients with any active autoimmune disease or immune deficiency or previous Guillain-Barre syndrome. Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g. patient with psoriatic arthritis are excluded) are eligible provided all of the following conditions are met:

• Rash that covers less than 10 % of body surface area.
• Disease is well controlled at baseline and requires only low-potency topical corticosteroids.
• No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months.
• Use of nonstandard neoadjuvant chemotherapy regimen, as determined by the Investigator.
• Female patients who are pregnant, breastfeeding, or of childbearing potential without a negative pregnancy test within 28 days (or decline contraception requirements as outlined above). Post-menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential.
• Patients unwilling or unable to comply with the protocol or provide informed consent.
• Any severe or uncontrolled medical condition or other condition that could affect participation in this study (in the opinion of the investigator), including but not limited to hyper/hypothyroidism, active systemic autoimmune disorders, untreated viral hepatitis or autoimmune hepatitis.
• Requires chronic treatment with a systemic steroid (⩾10 mg/day of prednisone equivalent) or with any systemic immunosuppressive agent.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 3 центра

• Baylor College of Medicine Medical Center - McNair Campus — Houston
• Baylor St. Lukes Medical Center — Houston
• Dan L. Duncan Cancer Center at Baylor College of Medicine — Houston

Идентификаторы

NCT: NCT04157127 · H-42434

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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