Chemotherapy combined with anakinra for pancreatic adenocarcinoma

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

This will try adding anakinra to pre- and post-operative chemotherapy in adults with resectable or locally advanced pancreatic adenocarcinoma to see if outcomes improve.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 24 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Baylor Research Institute (other)
• Drugs / interventions: canakinumab, chemotherapy, radiation
• Locations: 1 site (Dallas, Texas)
• Trial ID: NCT04926467 on ClinicalTrials.gov

What this trial studies

This is an open-label, single-arm phase II study at Baylor that gives anakinra together with perioperative chemotherapy for patients with pancreatic ductal adenocarcinoma planned for surgery. Participants receive preoperative nab-paclitaxel, gemcitabine and cisplatin, undergo surgery after a short anakinra break, then receive postoperative 5-fluorouracil, oxaliplatin and irinotecan, with growth factor support (Neupogen/Neulasta) to limit neutropenia. Anakinra is self-administered throughout the treatment period except for a two-day pause before surgery. Enrollment requires histologic/cytologic confirmation of PDAC, AJCC stage I–III (resectable, potentially resectable, or locally advanced), ECOG 0–1, and specified adequate blood and liver function.

Who should consider this trial

Good fit: Adults 18 or older with histologically confirmed pancreatic ductal adenocarcinoma (AJCC stage I–III; resectable, potentially resectable, or locally advanced), ECOG performance status 0–1, and adequate hematologic and liver function who are planned for perioperative chemotherapy and surgery are ideal candidates.

Not a fit: Patients with metastatic (stage IV) disease, ECOG ≥2, significant organ dysfunction, inability to receive the specified chemotherapies or self-inject anakinra, or inadequate blood counts are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, adding anakinra could reduce inflammation-driven tumor progression and improve surgical and longer-term outcomes for some patients.

How similar studies have performed: Preliminary clinical experience combining anakinra with chemotherapy in metastatic and localized PDAC has suggested tolerability and possible benefit, but perioperative use with this exact regimen has not been proven.

Eligibility criteria

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

Where this trial is running

Dallas, Texas

• Baylor University Medical Center, Charles A Sammons Cancer Center — Dallas, Texas, United States (RECRUITING)

Study contacts

• Principal investigator: A. Scott Paulson, MD — Charles A. Sammons Cancer Center/Texas Oncology
• Study coordinator: Page Blas, MA

Conditions: Pancreatic Adenocarcinoma