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A Pilot, Prospective, Non-randomized Evaluation of the Safety of Anakinra Plus Standard Chemotherapy

Phase 1
Conditions
Pancreas Cancer
Interventions
Registration Number
NCT02021422
Lead Sponsor
Baylor Research Institute
Brief Summary

The study's overall objectives are to evaluate the safety of anakinra in combination with standard chemotherapy regimens in patients with pancreatic ductal adenocarinoma, as well as to collect preliminary immune modulation and clinical activity information, overall survival, and serious adverse events related to the study drug.

Detailed Description

Kineret (anakinra) is a FDA-approved drug indicated for rheumatoid arthritis. Anakinra is a recombinant, nonglycosylated form of the human interleukin-1 receptor antagonist (IL-1Ra). Anakinra blocks the biologic activity of IL -1 by competitively inhibiting IL-1 binding to the interleukin-1 type I receptor (IL-1RI), which is expressed in a wide variety of tissues and organs. IL-1 production is induced in response to inflammatory stimuli and mediates various physiologic effects including inflammatory and immunological responses.

This is a pilot, prospective, non-randomized, consecutive enrollment study that will enroll up to 12 subjects who meet the study defined inclusion and exclusion criteria.

Subjects will undergo standard of care chemotherapy treatment/regimens (i.e., modified FOLFIRINOX). Subjects will be dispensed a 2 weeks supply of anakinra the day they begin chemotherapy. They will be instructed to begin self-administering the anakinra (study drug) injections the day after their first dose of chemotherapy.

They will have a blood sample collected at baseline and 6 months follow up. If they have surgery for their disease, they may have a tissue sample collected for later analysis.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
13
Inclusion Criteria
  • 18 years of age or older
  • Male or non-pregnant and non-lactating female
  • Confirmed metastatic/inoperable metastatic pancreas cancer and/or Histologically/cytologically confirmed metastatic adenocarcinoma of pancreas
  • Patients' blood counts and blood chemistry levels at baseline must be not clinically significant (NCS) as determined by the enrolling investigator.
  • Patient has Eastern Cooperative Oncology Group( ECOG ) Performance Status 0 to 2 (refer to Appendix 5):
  • Signed study consent form
Exclusion Criteria
  • <18 years of age
  • Pregnant or lactating female
  • Patient has islet cell neoplasms
  • Active secondary malignancies (2nd cancer not treated/present)
  • Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy
  • Known infection with hepatitis B, hepatitis C, or cirrhosis
  • Major surgery or vascular device placement (excluding ports for IV medication/chemotherapy) within 2 weeks prior to Day 1 of treatment in study
  • History of allergy or hypersensitivity to the study drugs
  • Patient is enrolled in any concurrent-outside (outside Baylor University Medical Center or Texas Oncology) clinical protocol or investigational trial
  • Significant cardiac disease as defined as New York Heart Association (NYHA) classification III or IV, uncontrolled CHF, or prior MI last 6-months
  • Any prior gastrointestinal (GI) disease or history of prior pelvic or abdominal radiation which in the opinion of the investigator may place the patient at increased risk
  • Peripheral sensory neuropathy ≥ to grade 2 at baseline
  • Significant co-morbidities deemed by investigator as unsuitable for participation/enrollment
  • Study consent form not signed

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Anakinra with Modified Folfirinoxanakinra8-weeks of anakinra and modified FOLFIRINOX regimen (refer to Appendix 9 for regimen) as follows Kineret (anakinra) Dosage Route Administration 100 mg SC Every Other Day Modified FOLFIRINOX Drug Dose Administration Oxaliplatin 85 mg/m2 2-4 hours Irinotecan 180 mg/m2 90 minutes fluorouracil 2400 mg/m2 48 hours
Anakinra with Modified FolfirinoxOxaliplatin8-weeks of anakinra and modified FOLFIRINOX regimen (refer to Appendix 9 for regimen) as follows Kineret (anakinra) Dosage Route Administration 100 mg SC Every Other Day Modified FOLFIRINOX Drug Dose Administration Oxaliplatin 85 mg/m2 2-4 hours Irinotecan 180 mg/m2 90 minutes fluorouracil 2400 mg/m2 48 hours
Anakinra with Modified FolfirinoxIrinotecan8-weeks of anakinra and modified FOLFIRINOX regimen (refer to Appendix 9 for regimen) as follows Kineret (anakinra) Dosage Route Administration 100 mg SC Every Other Day Modified FOLFIRINOX Drug Dose Administration Oxaliplatin 85 mg/m2 2-4 hours Irinotecan 180 mg/m2 90 minutes fluorouracil 2400 mg/m2 48 hours
Anakinra with Modified Folfirinoxfluorouracil8-weeks of anakinra and modified FOLFIRINOX regimen (refer to Appendix 9 for regimen) as follows Kineret (anakinra) Dosage Route Administration 100 mg SC Every Other Day Modified FOLFIRINOX Drug Dose Administration Oxaliplatin 85 mg/m2 2-4 hours Irinotecan 180 mg/m2 90 minutes fluorouracil 2400 mg/m2 48 hours
Primary Outcome Measures
NameTimeMethod
The Number of Participants with SAEs and AEs.6 months

Test the safety of Anakinra in combination with standard chemotherapy in patients with metastatic pancreatic ductal adenocarcinoma (PDAC) as evidenced by the Number of Participants with serious adverse events (SAEs) and adverse events (AEs).

Secondary Outcome Measures
NameTimeMethod
Overall Survival6 months

Overall Survival (OS) rate as defined by the percentage of people who are alive for a certain period of time after diagnosis

Adverse events associated with injection site reactions and the incidence of infections6 Months

Adverse events associated with injection site reactions and the incidence of infections

Data Collection: tumor measurements by CT scans6 months

Data Collection: tumor measurements by CT scans

Gather preliminary information on the immune modulation and clinical activity of this therapy6 month

* Blood transcriptional profiling

* Composition of white blood cells

* Assessment of PDAC antigen--specific T cell repertoire in the blood

Trial Locations

Locations (1)

Baylor Sammons Cancer Center

🇺🇸

Dallas, Texas, United States

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