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

Pancreas Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02021422
• Other study ID #: 013-018
• Status: Active, not recruiting
• Phase: Phase 1
• First received: December 20, 2013
• Last updated: January 30, 2017
• Start date: June 2013
• Est. completion date: December 2017

Study information

• Verified date: January 2017
• Source: Baylor Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 13
• Est. completion date: December 2017
• Est. primary completion date: December 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Adenocarcinoma
• Pancreas Cancer
• Pancreatic Neoplasms

Intervention

Drug:
• anakinra
Dosage Route Administration 100 mg SC Every Other Day
• Oxaliplatin
Oxaliplatin 85 mg/m2 2-4 hours
• Irinotecan
Irinotecan 180 mg/m2 90 minutes
• fluorouracil
fluorouracil 2400 mg/m2 48 hours

Locations

Country	Name	City	State
United States	Baylor Sammons Cancer Center	Dallas	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Baylor Research Institute

Country where clinical trial is conducted

United States, 

References & Publications (22)

Allantaz F, Chaussabel D, Stichweh D, Bennett L, Allman W, Mejias A, Ardura M, Chung W, Smith E, Wise C, Palucka K, Ramilo O, Punaro M, Banchereau J, Pascual V. Blood leukocyte microarrays to diagnose systemic onset juvenile idiopathic arthritis and follow the response to IL-1 blockade. J Exp Med. 2007 Sep 3;204(9):2131-44. Erratum in: J Exp Med. 2009 Sep 28;206(10):2299. Smith, Elisabeth [added]. — View Citation

Aspord C, Pedroza-Gonzalez A, Gallegos M, Tindle S, Burton EC, Su D, Marches F, Banchereau J, Palucka AK. Breast cancer instructs dendritic cells to prime interleukin 13-secreting CD4+ T cells that facilitate tumor development. J Exp Med. 2007 May 14;204(5):1037-47. — View Citation

Beatty GL, Chiorean EG, Fishman MP, Saboury B, Teitelbaum UR, Sun W, Huhn RD, Song W, Li D, Sharp LL, Torigian DA, O'Dwyer PJ, Vonderheide RH. CD40 agonists alter tumor stroma and show efficacy against pancreatic carcinoma in mice and humans. Science. 2011 Mar 25;331(6024):1612-6. doi: 10.1126/science.1198443. — View Citation

Bennett L, Palucka AK, Arce E, Cantrell V, Borvak J, Banchereau J, Pascual V. Interferon and granulopoiesis signatures in systemic lupus erythematosus blood. J Exp Med. 2003 Mar 17;197(6):711-23. — View Citation

Chaussabel D, Quinn C, Shen J, Patel P, Glaser C, Baldwin N, Stichweh D, Blankenship D, Li L, Munagala I, Bennett L, Allantaz F, Mejias A, Ardura M, Kaizer E, Monnet L, Allman W, Randall H, Johnson D, Lanier A, Punaro M, Wittkowski KM, White P, Fay J, Klintmalm G, Ramilo O, Palucka AK, Banchereau J, Pascual V. A modular analysis framework for blood genomics studies: application to systemic lupus erythematosus. Immunity. 2008 Jul 18;29(1):150-64. doi: 10.1016/j.immuni.2008.05.012. — View Citation

Coussens LM, Zitvogel L, Palucka AK. Neutralizing tumor-promoting chronic inflammation: a magic bullet? Science. 2013 Jan 18;339(6117):286-91. doi: 10.1126/science.1232227. Review. Erratum in: Science. 2013 Mar 29;339(6127):1522. — View Citation

De Monte L, Reni M, Tassi E, Clavenna D, Papa I, Recalde H, Braga M, Di Carlo V, Doglioni C, Protti MP. Intratumor T helper type 2 cell infiltrate correlates with cancer-associated fibroblast thymic stromal lymphopoietin production and reduced survival in pancreatic cancer. J Exp Med. 2011 Mar 14;208(3):469-78. doi: 10.1084/jem.20101876. — View Citation

Kalos M, Levine BL, Porter DL, Katz S, Grupp SA, Bagg A, June CH. T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia. Sci Transl Med. 2011 Aug 10;3(95):95ra73. doi: 10.1126/scitranslmed.3002842. — View Citation

Kuraishy A, Karin M, Grivennikov SI. Tumor promotion via injury- and death-induced inflammation. Immunity. 2011 Oct 28;35(4):467-77. doi: 10.1016/j.immuni.2011.09.006. Review. — View Citation

La Torre M, Nigri G, Ferrari L, Cosenza G, Ravaioli M, Ramacciato G. Hospital volume, margin status, and long-term survival after pancreaticoduodenectomy for pancreatic adenocarcinoma. Am Surg. 2012 Feb;78(2):225-9. Review. — View Citation

Laheru D, Jaffee EM. Immunotherapy for pancreatic cancer - science driving clinical progress. Nat Rev Cancer. 2005 Jun;5(6):459-67. Review. — View Citation

Lee HC, Ziegler SF. Inducible expression of the proallergic cytokine thymic stromal lymphopoietin in airway epithelial cells is controlled by NFkappaB. Proc Natl Acad Sci U S A. 2007 Jan 16;104(3):914-9. — View Citation

Maker AV, Katabi N, Qin LX, Klimstra DS, Schattner M, Brennan MF, Jarnagin WR, Allen PJ. Cyst fluid interleukin-1beta (IL1beta) levels predict the risk of carcinoma in intraductal papillary mucinous neoplasms of the pancreas. Clin Cancer Res. 2011 Mar 15;17(6):1502-8. doi: 10.1158/1078-0432.CCR-10-1561. — View Citation

Palucka AK, Gatlin J, Blanck JP, Melkus MW, Clayton S, Ueno H, Kraus ET, Cravens P, Bennett L, Padgett-Thomas A, Marches F, Islas-Ohlmayer M, Garcia JV, Banchereau J. Human dendritic cell subsets in NOD/SCID mice engrafted with CD34+ hematopoietic progenitors. Blood. 2003 Nov 1;102(9):3302-10. — View Citation

Palucka AK, Ueno H, Connolly J, Kerneis-Norvell F, Blanck JP, Johnston DA, Fay J, Banchereau J. Dendritic cells loaded with killed allogeneic melanoma cells can induce objective clinical responses and MART-1 specific CD8+ T-cell immunity. J Immunother. 2006 Sep-Oct;29(5):545-57. — View Citation

Palucka K, Banchereau J. Cancer immunotherapy via dendritic cells. Nat Rev Cancer. 2012 Mar 22;12(4):265-77. doi: 10.1038/nrc3258. Review. — View Citation

Pascual V, Allantaz F, Arce E, Punaro M, Banchereau J. Role of interleukin-1 (IL-1) in the pathogenesis of systemic onset juvenile idiopathic arthritis and clinical response to IL-1 blockade. J Exp Med. 2005 May 2;201(9):1479-86. — View Citation

Pedroza-Gonzalez A, Xu K, Wu TC, Aspord C, Tindle S, Marches F, Gallegos M, Burton EC, Savino D, Hori T, Tanaka Y, Zurawski S, Zurawski G, Bover L, Liu YJ, Banchereau J, Palucka AK. Thymic stromal lymphopoietin fosters human breast tumor growth by promoting type 2 inflammation. J Exp Med. 2011 Mar 14;208(3):479-90. doi: 10.1084/jem.20102131. — View Citation

Ramilo O, Allman W, Chung W, Mejias A, Ardura M, Glaser C, Wittkowski KM, Piqueras B, Banchereau J, Palucka AK, Chaussabel D. Gene expression patterns in blood leukocytes discriminate patients with acute infections. Blood. 2007 Mar 1;109(5):2066-77. — View Citation

Sebens Müerköster S, Werbing V, Sipos B, Debus MA, Witt M, Grossmann M, Leisner D, Kötteritzsch J, Kappes H, Klöppel G, Altevogt P, Fölsch UR, Schäfer H. Drug-induced expression of the cellular adhesion molecule L1CAM confers anti-apoptotic protection and chemoresistance in pancreatic ductal adenocarcinoma cells. Oncogene. 2007 Apr 26;26(19):2759-68. — View Citation

Vence L, Palucka AK, Fay JW, Ito T, Liu YJ, Banchereau J, Ueno H. Circulating tumor antigen-specific regulatory T cells in patients with metastatic melanoma. Proc Natl Acad Sci U S A. 2007 Dec 26;104(52):20884-9. — View Citation

Yu CI, Gallegos M, Marches F, Zurawski G, Ramilo O, García-Sastre A, Banchereau J, Palucka AK. Broad influenza-specific CD8+ T-cell responses in humanized mice vaccinated with influenza virus vaccines. Blood. 2008 Nov 1;112(9):3671-8. doi: 10.1182/blood-2008-05-157016. — View Citation

* Note: There are 22 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The Number of Participants with SAEs and AEs.	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).	6 months
Secondary	Overall Survival	Overall Survival (OS) rate as defined by the percentage of people who are alive for a certain period of time after diagnosis	6 months
Secondary	Adverse events associated with injection site reactions and the incidence of infections	Adverse events associated with injection site reactions and the incidence of infections	6 Months
Secondary	Data Collection: tumor measurements by CT scans	Data Collection: tumor measurements by CT scans	6 months
Secondary	Gather preliminary information on the immune modulation and clinical activity of this therapy	Blood transcriptional profiling; Composition of white blood cells; Assessment of PDAC antigen--specific T cell repertoire in the blood	6 month

External Links

•   Physician Package Insert Kineret (anakinra). FDA Website.