Clinical Trials /

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

NCT04157127

Description:

This is a phase 1, first in man, dose escalation study for safety and feasibility for administration of 3 doses of DC vaccine for pancreatic adenocarcinoma.

Related Conditions:
  • Pancreatic Adenocarcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: 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)

Clinical Trial IDs

  • ORG STUDY ID: H-42434
  • NCT ID: NCT04157127

Conditions

  • Pancreatic Adenocarcinoma
  • Pancreatic Cancer

Interventions

DrugSynonymsArms
Autologous DC vaccineAutologous DC Vaccine Cohort 1

Purpose

This is a phase 1, first in man, dose escalation study for safety and feasibility for administration of 3 doses of DC vaccine for pancreatic adenocarcinoma.

Detailed Description

      The primary objective of this phase 1, first in man trial is to determine the safety,
      toxicity, and feasibility of delivering autologous dendritic cells (DCs) loaded with
      pancreatic adenocarcinoma lysate plus mRNA to pancreatic cancer patients as adjuvant therapy
      following completion of standard chemotherapy.

      Patients will first complete standard treatment for pancreatic adenocarcinoma which is
      surgically resectable and then within 3 months of finishing chemotherapy, they will have
      three doses of the dendritic cell vaccine by perinodal injection using ultrasound guidance.
    

Trial Arms

NameTypeDescriptionInterventions
Autologous DC Vaccine Cohort 1ExperimentalVaccine made from autologous dendritic cells loaded with tumor cell lysate and RNA. Subject will get 3 doses of DC vaccine (one every 14 days) and be monitored (vital signs every 30 minutes) for 2 hours after each dose. During treatment, subjects get weekly peg-interferon a-2b at 1.5 mcg/kg on the first day of vaccination up through 14 days after last vaccination. DC Vaccine dose evaluated in Cohort 1: st vaccine - 0.5 million cells nd vaccine - 1 million cells rd vaccine - 2 million cells At each dose level, the 1st subject should get all 3 vaccinations before the 2nd and 3rd subjects at that level receive their 1st vaccination. The 3rd subject can begin vaccination regardless of the time since the 2nd subject began vaccinations. All 3 subjects in cohort should get all 3 vaccinations before any subjects are treated in the next higher cohort. Because of this, the study may not progress to every dose level before MTD is found.
  • Autologous DC vaccine
Autologous DC Vaccine Cohort 2ExperimentalVaccine made from autologous dendritic cells loaded with tumor cell lysate and RNA. Subject will get 3 doses of DC vaccine (one every 14 days) and be monitored (vital signs every 30 minutes) for 2 hours after each dose. During treatment, subjects get weekly peg-interferon a-2b at 1.5 mcg/kg on the first day of vaccination up through 14 days after last vaccination. DC Vaccine dose evaluated in Cohort 2: st vaccine - 1 million cells nd vaccine - 2 million cells rd vaccine - 4 million cells At each dose level, the 1st subject should get all 3 vaccinations before the 2nd and 3rd subjects at that level receive their 1st vaccination. The 3rd subject can begin vaccination regardless of the time since the 2nd subject began vaccinations. All 3 subjects in cohort should get all 3 vaccinations before any subjects are treated in the next higher cohort. Because of this, the study may not progress to every dose level before MTD is found.
  • Autologous DC vaccine
Autologous DC Vaccine Cohort 3ExperimentalVaccine made from autologous dendritic cells loaded with tumor cell lysate and RNA. Subject will get 3 doses of DC vaccine (one every 14 days) and be monitored (vital signs every 30 minutes) for 2 hours after each dose. During treatment, subjects get weekly peg-interferon a-2b at 1.5 mcg/kg on the first day of vaccination up through 14 days after last vaccination. DC Vaccine dose evaluated in Cohort 3: st vaccine - 2 million cells nd vaccine - 4 million cells rd vaccine - 8 million cells At each dose level, the 1st subject should get all 3 vaccinations before the 2nd and 3rd subjects at that level receive their 1st vaccination. The 3rd subject can begin vaccination regardless of the time since the 2nd subject began vaccinations. All 3 subjects in cohort should get all 3 vaccinations before any subjects are treated in the next higher cohort. Because of this, the study may not progress to every dose level before MTD is found.
  • Autologous DC vaccine
Autologous DC Vaccine Cohort 4ExperimentalVaccine made from autologous dendritic cells loaded with tumor cell lysate and RNA. Subject will get 3 doses of DC vaccine (one every 14 days) and be monitored (vital signs every 30 minutes) for 2 hours after each dose. During treatment, subjects get weekly peg-interferon a-2b at 1.5 mcg/kg on the first day of vaccination up through 14 days after last vaccination. DC Vaccine dose evaluated in Cohort 4: st vaccine - 6 million cells nd vaccine - 6 million cells rd vaccine - 6 million cells At each dose level, the 1st subject should get all 3 vaccinations before the 2nd and 3rd subjects at that level receive their 1st vaccination. The 3rd subject can begin vaccination regardless of the time since the 2nd subject began vaccinations. All 3 subjects in cohort should get all 3 vaccinations before any subjects are treated in the next higher cohort. Because of this, the study may not progress to every dose level before MTD is found.
  • Autologous DC vaccine
Autologous DC Vaccine Cohort 5ExperimentalVaccine made from autologous dendritic cells loaded with tumor cell lysate and RNA. Subject will get 3 doses of DC vaccine (one every 14 days) and be monitored (vital signs every 30 minutes) for 2 hours after each dose. During treatment, subjects get weekly peg-interferon a-2b at 1.5 mcg/kg on the first day of vaccination up through 14 days after last vaccination. DC Vaccine dose evaluated in Cohort 5: st vaccine - 7 million cells nd vaccine - 7 million cells rd vaccine - 7 million cells At each dose level, the 1st subject should get all 3 vaccinations before the 2nd and 3rd subjects at that level receive their 1st vaccination. The 3rd subject can begin vaccination regardless of the time since the 2nd subject began vaccinations. All 3 subjects in cohort should get all 3 vaccinations before any subjects are treated in the next higher cohort. Because of this, the study may not progress to every dose level before MTD is found.
  • Autologous DC vaccine
Autologous DC Vaccine Cohort 6ExperimentalVaccine made from autologous dendritic cells loaded with tumor cell lysate and RNA. Subject will get 3 doses of DC vaccine (one every 14 days) and be monitored (vital signs every 30 minutes) for 2 hours after each dose. During treatment, subjects get weekly peg-interferon a-2b at 1.5 mcg/kg on the first day of vaccination up through 14 days after last vaccination. DC Vaccine dose evaluated in Cohort 6: st vaccine - 8 million cells nd vaccine - 8 million cells rd vaccine - 8 million cells At each dose level, the 1st subject should get all 3 vaccinations before the 2nd and 3rd subjects at that level receive their 1st vaccination. The 3rd subject can begin vaccination regardless of the time since the 2nd subject began vaccinations. All 3 subjects in cohort should get all 3 vaccinations before any subjects are treated in the next higher cohort. Because of this, the study may not progress to every dose level before MTD is found.
  • Autologous DC vaccine

Eligibility Criteria

        Step 1 Inclusion Criteria:

          -  Provision of signed and dated informed consent form for Step 1

          -  Male or female, aged 18 years and older

          -  Diagnosed with adenocarcinoma of the pancreas deemed to be potentially resectable and
             who are deemed to be good candidate for postoperative adjuvant chemotherapy. This may
             include patients whose tumors are deemed suitable for upfront resection as well as
             patients whose tumors are deemed borderline resectable and thus undergo neoadjuvant
             therapy prior to resection. Note: women of child-bearing potential must be on birth
             control for 30 days prior to first vaccination; it is recommended to discuss this
             requirement with subjects at Step 1.

        Step 1 Exclusion Criteria:

          -  Locally advanced tumors deemed un-resectable and/or metastatic tumors

          -  Patients with known HIV positivity

          -  Patients with active HBV and HCV infection

          -  Patients with any history of autoimmune disease

          -  History of concussion

        Step 2 Inclusion Criteria:

          -  Provision of signed and dated informed consent form for Step 2

          -  Must have undergone standard adjuvant/neo-adjuvant chemotherapy and surgery, as deemed
             by Investigator.

          -  Must have completed standard care within 6 weeks of step 2 registration.

          -  Must have adequate tissue obtained from surgery, as determined and confirmed by Dr.
             Decker.

          -  Adequate kidney, liver, bone marrow function, and immune function, as follows, within
             28 days prior to step 2 registration: Hemoglobin greater than/equal to 8 gm/dL;
             Absolute neutrophil count (ANC) greater than/equal to 1,500 cells/mm3; Platelet count
             greater than/equal to 75,000/mm3; Total bilirubin less than/equal to 1.5 times upper
             limit of normal (ULN); Aspartate transaminase AST (SGOT) and alanine aminotransferase
             ALT (SGPT) less than/equal to 2.5 times the ULN; TSH range between 0.4-4.0 mIU/L; RF
             less than/equal to 15 IU/ml; Peripheral CD4+ t-cell greater than 200/ul.

          -  Negative Hepatitis B and C serology. Positive HBs Ab indicating immunity is not
             exclusionary.

          -  ECOG performance status less than/equal to 2

          -  For women of child bearing potential (WOCBP): At the time or (or prior to)
             registration to Step 2, use of highly effective contraception must be discussed with
             participant. NOTE: Patient must agree to start contraception at least 30 days before
             first vaccination and continue for at least 12 weeks after his/her last vaccination.

          -  WOCBP must have a negative serum pregnancy within 28 days of registration to step 2.

          -  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.

        Step 2 Exclusion Criteria:

          -  Use of nonstandard adjuvant chemotherapy regimen, as determined by the Investigator.

          -  Female patients who are pregnant, breast feeding, or of childbearing potential without
             a negative pregnancy test within 28 days of registration to Step 2 (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, systemic autoimmune disorders, untreated viral
             hepatitis or autoimmune hepatitis.

          -  Treatment with a systemic steroid or with any systemic immunosuppressive agent within
             7 days of step 2 registration.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:MTD of DC Vaccine
Time Frame:From treatment start until 6 weeks after.
Safety Issue:
Description:Maximum tolerated dose of dendritic cell vaccine following completion of surgery and standard adjuvant chemotherapy, as determined by BOIN design. DLTs were defined as shown in the subsequent Primary Outcome Measure.

Secondary Outcome Measures

Measure:Time to Recurrence
Time Frame:From surgery until recurrence or up to 3 years after surgery, whichever comes first.
Safety Issue:
Description:Measurement of time from resection surgery to recurrence of pancreatic adenocarcinoma.
Measure:Overall Survival
Time Frame:From surgery until death or up to 3 years after surgery, whichever comes first.
Safety Issue:
Description:Measurement of time from resection surgery to death.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Baylor College of Medicine

Trial Keywords

  • Immunotherapy
  • Adjuvant therapy

Last Updated

November 6, 2019