Clinical trial NCT04157127: Th-1 Dendritic Cell Immunotherapy Plus Standard Chemotherapy for Pancreatic Adenocarcinoma
Official title: Phase I Study of Th-1 Dendritic Cell Immunotherapy in Combination With Standard Chemotherapy for the Adjuvant Treatment of Pancreatic Adenocarcinoma (DECIST)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Pancreatic Adenocarcinoma
Pancreatic Cancer
Pancreatic Adenosquamous Carcinoma
Keywords: Immunotherapy
Adjuvant therapy
Cell Therapy
Lead sponsor: Diakonos Oncology Corporation
Sponsor class: INDUSTRY
Collaborators: name: Baylor College of Medicine
First posted: 2019-11-08
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: This is a single-arm, open-label study where all subjects will receive the DC therapy. The number of cells administered will vary based on the group/cohort determination. Group A receives intervention after neoadjuvant chemotherapy, surgery and adjuvant chemotherapy. Group B contains 2 cohorts (low and high dose) with intervention (1st cycle) after surgery, but before adjuvant chemotherapy with the option for intervention after adjuvant chemotherapy (2nd cycle).
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria

An individual must meet all of the following criteria:

1. Provision of signed and dated informed consent form
2. Male or female, aged 18 years and older
3. 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.
4. Adequate kidney, liver, bone marrow function, and immune function, as follows, within 28 days prior to registration:

   1. Hemoglobin ≥ 8.0 gm/dL
   2. Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3
   3. Platelet count ≥ 75,000 /mm3
   4. Total bilirubin ≤ 1.5 times upper limit of normal (ULN),
   5. Aspartate transaminase AST (SGOT) and alanine aminotransferase ALT (SGPT) ≤ 2.5 times the ULN
5. ECOG performance status ≤ 2.
6. 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.
7. WOCBP must have a negative serum pregnancy prior to vaccination
8. 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.
9. Patient must agree to not donate blood for up to 90 days after last vaccination.

Exclusion Criteria

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

1. Unresectable or metastatic (stage IV) pancreatic cancer.
2. Patients with known HIV and a positive viral load.
3. 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.
4. 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:

   1. Rash that covers less than 10 % of body surface area.
   2. Disease is well controlled at baseline and requires only low-potency topical corticosteroids.
   3. 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.
5. Use of nonstandard neoadjuvant chemotherapy regimen, as determined by the Investigator.
6. 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.
7. Patients unwilling or unable to comply with the protocol or provide informed consent.
8. 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.
9. Requires chronic treatment with a systemic steroid (⩾10 mg/day of prednisone equivalent) or with any systemic immunosuppressive agent.

Primary outcomes:
measure: Safety of DC Therapy
timeFrame: From treatment start until 6 weeks after.
measure: Number of participants who experienced Dose Limiting Toxicities (DLTs)
timeFrame: From treatment start until 6 weeks after.
Secondary outcomes:
measure: Recurrence-Free Survival
timeFrame: From surgery until recurrence or up to 3 years after surgery, whichever comes first.
measure: Overall Survival
timeFrame: From surgery until death or up to 3 years after surgery, whichever comes first.
Other outcomes:
Locations:
city: Houston
country: United States
facility: Baylor College of Medicine Medical Center - McNair Campus
state: Texas
city: Houston
country: United States
facility: Baylor St. Lukes Medical Center
state: Texas
city: Houston
country: United States
facility: Dan L. Duncan Cancer Center at Baylor College of Medicine
state: Texas
Study officials:
affiliation: Baylor College of Medicine
name: Benjamin Musher, MD
role: PRINCIPAL_INVESTIGATOR
References: