Gemcitabine, Nab-Paclitaxel, Cisplatin and Anakinra Treatment on Patients With Pancreatic Cancer

A Pilot Study of Gemcitabine, Nab-Paclitaxel, Cisplatin and Anakinra Treatment on Patients With Resectable or Potentially Resectable Pancreatic Adenocarcinoma (PDAC)

The objective of this study is to improve survival by the addition of anakinra to the chemotherapy combination of nab-paclitaxel, gemcitabine, and cisplatin in patients with resectable or potentially resectable pancreatic adenocarcinoma (PDAC). The primary endpoint of the study is to determine whether the combination of abraxane, gemcitabine, cisplatin, and anakinra will improve disease-free survival (DFS) and to determine the number of patients who meet or surpass 11.5 months of DFS.

The secondary objectives of this study are to evaluate the effect of anakinra when combined with the three-drug regimen of nab-paclitaxel, gemcitabine, and cisplatin on response rate and overall survival after diagnosis and adverse events of patients with resectable or potentially resectable PDAC. The investigators will use the benchmark of 24 months overall survival (OS) to determine how many patients meet or exceed this goal. The investigators will monitor, by survey, patients' health related quality of life while on treatment to determine if the addition of anakinra improves this measure.

Study Overview

• Status: Completed
• Conditions: Pancreatic Adenocarcinoma
• Intervention / Treatment: Drug: Nab-paclitaxel; Drug: Gemcitabine; Drug: Cisplatin; Drug: Anakinra

Detailed Description

This is a single-arm, open-label pilot study. Patients will receive Nab-paclitaxel, gemcitabine, cisplatin and anakinra.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75246
      • Baylor 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. Male or female ≥ 18 years of age.
2. Suspected PDAC prior to diagnosis or histological diagnosis of adenocarcinoma of the pancreas confirmed by pathology. Mixed subtypes of adenocarcinoma are acceptable as long as majority of cells are ductal adenocarcinoma. Subjects with suspected PDAC are those without a biopsy and a pancreas mass which appears to be metastatic disease. These subjects will be enrolled prior to biopsy and then excluded if a diagnosis of pancreas cancer is not confirmed by histology.
3. American Joint Committee on Cancer (AJCC) Stage I-III Pancreatic carcinoma.
4. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2.
5. Serum albumin ≥2.0 gm/dL.
6. Expected survival ≥6 months.

7. Adequate hematologic function as defined by:

   • Absolute neutrophil count (ANC) >1500/mm3
   • Platelets ≥70,000/mm3
   • Hemoglobin >9 g/dL (in the absence of red blood transfusion).

8. Adequate liver function, as defined by:

   • Serum total bilirubin ≤2 x ULN mg/dL, prior to initiation of treatment.
   • Alanine transaminase (ALT) and aspartate aminotransferase (AST) ≤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. All females of child bearing potential must agree to use contraception to avoid pregnancy throughout the study and for one month after the last dose.
11. Patients must be accessible for treatment and follow-up.
12. Patients must have the ability to understand the study, its inherent risks, side effects and potential benefits and be able to give written informed consent to participate. Patients may not be consented by a medical power of attorney.

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. Other malignancy within five years, unless the probability of recurrence of the prior malignancy is <5% as determined by the Principal Investigator based on available information.
4. Current, active immunosuppressive therapy such as cyclosporine, tacrolimus
5. Significant or uncontrolled congestive heart failure (CHF), myocardial infarction or significant ventricular arrhythmias within the last 6 months.
6. Active infection or antibiotics within 48 hours prior to study enrollment, including unexplained fever (temp > 38°C).
7. Other severe and/or uncontrolled medical conditions or other conditions that in the opinion of the investigator could affect the participation of the patient on the study.
8. Study consent form not signed.
9. Pregnant or nursing women.
10. Known HIV positive status.

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: All Patients; All patients will receive Nab-paclitaxel, Gemcitabine, Cisplatin, and Anakinra given on Day 1 and 8 of a 21 day cycle (two weeks on with one week rest). Anakinra will be self-administered subcutaneously corresponding with chemotherapy. The patient will complete a total of 6 cycles of chemotherapy.	Drug: Nab-paclitaxel; 125 mg/m2; Other Names: Abraxane; Drug: Gemcitabine; 1000 mg/m2; Other Names: Gemzar ®; Drug: Cisplatin; 25 mg/m2; Other Names: Platinol; Drug: Anakinra; 100 mg; Other Names: Kineret

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Free Survival (DFS)	determine the number of patients who meet or surpass 11.5 months of disease free survival	2 Years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	The use of a benchmark of 24 months overall survival will be used to determine how many patients meet or exceed this goal.	2 years
Quality of Life	The use of surveys will capture the patients' health-related quality life while on treatment to determine if the addition of anakinra improves this measure.	2 years
Toxicities and Adverse Events will be graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.	Toxicities and adverse events will be recorded from the of informed consent to 30 days following the last study treatment.	2 years

Collaborators and Investigators

• Sponsor: Baylor Research Institute
• Investigators: Principal Investigator: Carlos Becerra, MD, Baylor Research Institute/Texas Oncology

Study record dates

Study Major Dates

• Study Start: January 1, 2016
• Primary Completion (Actual): June 14, 2021
• Study Completion (Actual): June 14, 2021

Study Registration Dates

• First Submitted: September 14, 2015
• First Submitted That Met QC Criteria: September 14, 2015
• First Posted (Estimate): September 15, 2015

Study Record Updates

• Last Update Posted (Actual): June 22, 2021
• Last Update Submitted That Met QC Criteria: June 21, 2021
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: resectable; Pancreatic adenocarcinoma; PDAC; potentially resectable
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Gemcitabine; Paclitaxel; Interleukin 1 Receptor Antagonist Protein
• Other Study ID Numbers: 015-198