Chemotherapy + Anakinra in Patients With Pancreatic Adenocarcinoma (PDAC)

An Open Label, Phase II Study of Chemotherapy + Anakinra in Patients With Resectable, Locally Advanced or Potentially Resectable Pancreatic Adenocarcinoma (PDAC)

Based on a central role of inflammation in pancreas cancer, the role of IL 1 in acute and chronic inflammation , the inhibitory effect of IL 1 alfa and beta by anakinra and preliminary experience with anakinra in combination with chemotherapy in metastasis (with FOLFIRINOX) and localized disease (with gemcitabine/abraxane/cisplatin), a phase 2 study with anakinra in combination with perioperative chemotherapy for patients with PDAC is being proposed.

Study Overview

• Status: Not yet recruiting
• Conditions: Pancreatic Adenocarcinoma
• Intervention / Treatment: Drug: Anakinra

Detailed Description

This is an open-label, single-arm, prospective phase II study conducted by Baylor Scott and White Research Institute in Dallas.

The study will enroll patients with pancreatic adenocarcinoma that are planned to receive pre-operative chemotherapy followed by surgical resection and post operative treatment. Local surgical/biopsy and pathology reports will constitute adequate documentation of histology/cytology for study inclusion.

Patients will receive pre- and post-operative chemotherapy plus Anakinra. Specifically, the pre-operative chemotherapy regimen will be a combination of Nab-paclitaxel, gemcitabine and cisplatin, while post-operative chemotherapy will use 5-Fluorouracil, oxaliplatin, and irinotecan. Patients will also receive growth factor (Neupogen followed by Neulasta) for safety and to ensure that treatment is not delayed due to neutropenic effects of chemotherapy.

Anakinra will be self-administered by the participants through out the treatment period. A treatment break of 2 days will be given prior to the surgery day.

• Study Type: Interventional
• Enrollment (Anticipated): 24
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Heather Williams, MS; Phone Number: (214) 818-7879; Email: Heather.Williams1@BSWHealth.org
• Study Contact Backup: Name: Joyce Ghormley; Phone Number: (214) 818-8961; Email: Joyce.Ghormley@BSWHealth.org

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75246
      • Baylor University Medical Center, Charles A Sammons Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• A patient will be eligible for inclusion in this study if he or she meets all of the following criteria:

  1. 18 years of age or older
  2. Histologically or Cytologically confirmed pancreatic ductal adenocarcinoma. Mixed subtypes of adenocarcinoma are acceptable as long as majority of cells are ductal adenocarcinoma.
  3. Resectable, locally advanced or potentially resectable pancreatic adenocarcinoma
  4. American Joint Committee on Cancer (AJCC) Stage I-III Pancreatic carcinoma.
  5. Patient has Eastern Cooperative Oncology Group( ECOG ) Performance Status 0 to 1
  6. Serum albumin ≥2.0 g/dL.

  7. Adequate hematologic function as defined by:

     1. Absolute neutrophil count (ANC) ≥1500/mm3;
     2. Platelets ≥70,000 x 10^3/µl;
     3. Hemoglobin ≥9 g/dL (in the absence of red blood transfusion).

  8. Adequate liver function, as defined by:

     1. Serum total bilirubin ≤2 x ULN mg/dL, prior to initiation of treatment.
     2. ALT (SGPT) and AST (SGOT) ≤2.5 x upper limit of normal (ULN).
  9. Adequate renal function, as defined by serum creatinine≤ 1.5 x ULN, or creatinine clearance ≥50 mL/min
  10. Women of child bearing potential and men must agree to use contraception throughout the study and for one month after the last anakinra administration.
  11. Subjects must understand and sign the informed consent form
  12. Patients must be accessible for treatment and follow-up.

Exclusion Criteria:

• A patient will be ineligible for inclusion in this study if he or she meets any of the following criteria:

  1. <18 years of age
  2. History of organ transplant.
  3. Patients with islet cell neoplasms
  4. Patients with stage IV pancreatic carcinoma
  5. Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy
  6. Known active infection with hepatitis B or hepatitis C
  7. Presence of clinically significant cirrhosis as determined by the investigator
  8. Known HIV positive status.
  9. Current, active immunosuppressive therapy such as cyclosporine, tacrolimus, etc.
  10. Major surgery or vascular device placement within 2 weeks prior to Day 1 of treatment in study
  11. Prior chemotherapy or radiation for pancreatic cancer
  12. History of allergy or hypersensitivity to the study drugs
  13. Patient is enrolled in any outside therapeutic clinical protocol or investigational trial with an investigational drug within 5 half-lives prior to Study ID assignment
  14. Previous or current treatment with anakinra, canakinumab or any other IL-1 inhibitor
  15. Other malignancy within five years(except cutaneous, non-melanoma malignancies or cervical carcinoma in site), unless the probability of recurrence of the prior malignancy is <5% as determined by the Principal Investigator based on available information.
  16. Significant cardiac disease (uncontrolled congestive heart failure (CHF), myocardial infarction or significant ventricular arrhythmias) within the last six months.
  17. Other severe and/or uncontrolled medical conditions (e.g: prior gastrointestinal (GI) disease or history of prior pelvic or abdominal radiation) or other conditions deemed by investigator as unsuitable for participation/enrollment
  18. Peripheral sensory neuropathy > or equal to grade 2 at baseline

  19. Abnormal liver function tests as follows:

      1. Total bilirubin of > 2 x ULN
      2. AST or ALT > 5x ULN
  20. Serum albumin ˂ 2.0 g/dL.

  21. Abnormal hematologic function as follows :

      1. Absolute neutrophil count (ANC) ˂ 1500/mm3;
      2. Platelets ˂ 70,000 x 10^3/µl;
      3. Hemoglobin ˂ 9 g/dL (in the absence of red blood transfusion).
  22. Pregnant or nursing women
  23. No signed Informed consent form

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Anakinra plus Chemotherapy; Patients will receive Anakinra during both pre-operative chemotherapy with Nab-paclitaxel, gemcitabine and cisplatin, followed by surgery and post-operative chemotherapy with 5-fluorouracil, oxaliplatin, and irinotecan.

Drug: Anakinra; Pre-operative treatment: Nab-paclitaxel (125 mg/m2), gemcitabine (1000 mg/m2), and cisplatin (25 mg/m2) will be given on Day 1 and 8 of a 21-day cycle. Patients will receive anakinra 100 mg injection twice a day starting on day 1 of chemotherapy. Anakinra will be self-administered by the patients and will be discontinued 2 days prior to surgery. Total number of cycles = 4. Post-operative treatment: 5-Fluorouracil (2400 mg/m2 CI for 48 hours), oxaliplatin (85 mg/m2), and irinotecan (150 mg/m2) will be given once every 2 weeks (1 cycle =14 days). Patients will receive anakinra 100 mg injection subcutaneously twice a day starting on day 1 of chemotherapy (initiated within 4-8 weeks after surgery). Anakinra will be self-administered by the patient throughout the treatment without any break. Total number of cycles = 8.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To determine the percentage of patients that have a normalization of CA19-9 after pre-op treatment with the combination of nab-paclitaxel (abraxane), gemcitabine, cisplatin and anakinra.	24 months

Secondary Outcome Measures

Outcome Measure	Time Frame
To determine the effect of anakinra in combination with perioperative chemotherapy on overall survival (OS) of PDAC patients. A benchmark of 24 months OS will be used to determine how many patients meet or exceed this goal.	24 months
To determine the effect of anakinra in combination with perioperative chemotherapy on the median disease free survival (DFS). A benchmark of 12 months DFS will be used to determine how many patients meet or exceed this goal.	12 months
To determine the effect of anakinra in combination with perioperative chemotherapy on response rate	24 months
To determine the R0 resection rates (complete tumor removal with negative resection margins) obtained with anakinra + pre-operative chemotherapy.	24 months
To describe the effect of anakinra in combination with perioperative chemotherapy on the prevalence and severity of pain by monitoring patients' pain level using memorial pain assessment card (MPAC).	24 months
To determine the effect of anakinra in combination with perioperative chemotherapy on patients' health-related quality of life by monitoring patients using EORTC quality of life survey questionnaire (EORTC QLQ-C30).	24 months
To determine the effect of anakinra in combination with perioperative chemotherapy on the inflammasomes ( IL6, CRP, IL1α and IL1β) in blood and in the resected pathology specimens.	24 months

Collaborators and Investigators

• Sponsor: Baylor Research Institute
• Investigators: Principal Investigator: Carlos Becerra, MD, Charles A. Sammons Cancer Center/Texas Oncology

Study record dates

Study Major Dates

• Study Start (Anticipated): June 1, 2021
• Primary Completion (Anticipated): June 1, 2025
• Study Completion (Anticipated): June 1, 2026

Study Registration Dates

• First Submitted: June 1, 2021
• First Submitted That Met QC Criteria: June 8, 2021
• First Posted (Actual): June 15, 2021

Study Record Updates

• Last Update Posted (Actual): June 15, 2021
• Last Update Submitted That Met QC Criteria: June 8, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Antirheumatic Agents; Interleukin 1 Receptor Antagonist Protein
• Other Study ID Numbers: 020-476

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes