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

Sponsor

Baylor Research Institute (Other)

Overall Status

Unknown status

CT.gov ID

NCT02021422

Collaborator

(none)

Enrollment

Location

Arm

Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Pancreas Cancer	Drug: anakinra Drug: Oxaliplatin Drug: Irinotecan Drug: fluorouracil	Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

13 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Pilot, Prospective, Non-randomized Evaluation of the Safety of Anakinra Plus Standard Chemotherapy Regimens in Metastatic Pancreatic Ductal Adenocarcinoma Patients

Study Start Date :

Jun 1, 2013

Anticipated Primary Completion Date :

Dec 1, 2017

Anticipated Study Completion Date :

Dec 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Other: Anakinra with Modified Folfirinox 8-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	Drug: anakinra Dosage Route Administration 100 mg SC Every Other Day Other Names: Kineret Drug: Oxaliplatin Oxaliplatin 85 mg/m2 2-4 hours Drug: Irinotecan Irinotecan 180 mg/m2 90 minutes Other Names: Camptosar Drug: fluorouracil fluorouracil 2400 mg/m2 48 hours Other Names: 5 FU

Arm

Intervention/Treatment

Other: Anakinra with Modified Folfirinox

8-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

Drug: anakinra

Dosage Route Administration 100 mg SC Every Other Day

Other Names:

Kineret

Drug: Oxaliplatin

Oxaliplatin 85 mg/m2 2-4 hours

Drug: Irinotecan

Irinotecan 180 mg/m2 90 minutes

Other Names:

Camptosar

Drug: fluorouracil

fluorouracil 2400 mg/m2 48 hours

Other Names:

5 FU

Outcome Measures

Primary Outcome Measures

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

Overall Survival [6 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 infections [6 Months]
Adverse events associated with injection site reactions and the incidence of infections
Data Collection: tumor measurements by CT scans [6 months]
Data Collection: tumor measurements by CT scans
Gather preliminary information on the immune modulation and clinical activity of this therapy [6 month]
Blood transcriptional profiling Composition of white blood cells Assessment of PDAC antigen--specific T cell repertoire in the blood

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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