Lag-3 and Gemcitabine for Treatment of Advanced Pancreas Cancer
NCT ID: NCT00732082
Last Updated: 2013-06-12
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
TERMINATED
PHASE1
18 participants
INTERVENTIONAL
2009-02-28
2012-09-30
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
AG-013736 In Combination With Gemcitabine Versus Gemcitabine Alone For Patients With Metastatic Pancreatic Cancer
NCT00219557
ARQ-761 Treatment With Gemcitabine/Nab-Paclitaxel Chemotherapy In Pancreatic Cancer
NCT02514031
Adenocarcinoma of the Pancreas Treated With Panitumumab and Gemcitabine Regimen to Investigate Overall Survival as Primary Endpoint
NCT00613730
Intra-arterial Gemcitabine vs. IV Gemcitabine and Nab-Paclitaxel Following Radiotherapy for LAPC
NCT03257033
A Trial Comparing Gemcitabine With and Without IMM-101 in Advanced Pancreatic Cancer
NCT01303172
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Primary Objectives
* To evaluate the safety and tolerability of repeated IMP321 subcutaneous injections in patients being treated with gemcitabine for advanced pancreas cancer.
* To determine any dose limiting toxicities of IMP321 in patients being treated with gemcitabine for advanced pancreas cancer.
Secondary Objectives
* To describe the pharmacokinetics of the last IMP321 subcutaneous injection compared to the first one, in a limited number of patients.
* To determine the pharmacodynamics of IMP321 therapy by:
* Quantify peripheral blood Treg (CD4+CD25+FoxP3+ T cells) in pancreatic cancer patients before and during treatment with IMP321 by flow cytometry.
* Evaluate the B- and T-cell responses to the pancreatic cancer-expressed antigen, mesothelin, by testing for antibodies and T-cell response by ELISpot.
* To evaluate the clinical response and time to disease progression with computed tomography examinations at two month intervals (current standard of care in gemcitabine-treated patients).
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
NON_RANDOMIZED
SINGLE_GROUP
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Dose Level 0
Gemcitabine (1 mg/m2 over 30 min) will be given on days 1, 8, and 15 of a 28 day cycle.
Gemcitabine
Dose Level 1
Gemcitabine (1 mg/m2 over 30 min) will be given on days 1, 8, and 15 of a 28 day cycle.
IMP321 3 mg SQ anterior surface of either the right or left thigh on Day 2.
The subsequent doses will be given by subcutaneous injection on the contralateral thigh.
Each single injection will be separated by a 13-day administration free period.
Gemcitabine
LAG-3
Dose Level 2
Gemcitabine (1 mg/m2 over 30 min) will be given on days 1, 8, and 15 of a 28 day cycle.
IMP321 6.5 mg SQ anterior surface of either the right or left thigh on Day 2.
The subsequent doses will be given by subcutaneous injection on the contralateral thigh.
Each single injection will be separated by a 13-day administration free perio
Gemcitabine
LAG-3
Dose Level 3
Gemcitabine (1 mg/m2 over 30 min) will be given on days 1, 8, and 15 of a 28 day cycle.
IMP321 13 mg SQ anterior surface of either the right or left thigh on Day 2.
The subsequent doses will be given by subcutaneous injection on the contralateral thigh.
Each single injection will be separated by a 13-day administration free perio
Gemcitabine
LAG-3
Dose Level 4
Gemcitabine (1 mg/m2 over 30 min) will be given on days 1, 8, and 15 of a 28 day cycle.
IMP321 26 mg SQ anterior surface of either the right or left thigh on Day 2.
The subsequent doses will be given by subcutaneous injection on the contralateral thigh.
Each single injection will be separated by a 13-day administration free perio
Gemcitabine
LAG-3
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Gemcitabine
LAG-3
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* Patient must have advanced disease (characterized by metastasis or locally advanced disease), or unable to undergo surgical treatment due to extent of disease or pre-existing health conditions precluding surgical treatment.
* Measurable or evaluable disease: RECIST Criteria will be used to assess and survey extent of disease
* Patients must be ≥ 18 years old.
* Performance Status: Karnofsky Performance Status (KPS) ≥ 70
* Life Expectancy \> 12 weeks.
* No previous history of chemotherapy for pancreas cancer in the metastatic setting prior to the start of protocol treatment.
* Patients must have recovered from uncontrolled, intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris or cardiac arrhythmia.
* Patients must have adequate bone marrow function defined as an absolute neutrophil count \>1,500/mm3, platelet count \>100,000/mm3 and hemoglobin \>10 g/dl.
* Patients must have adequate renal function defined as serum creatinine ≤ 2.0 mg/dl or creatinine clearance ≥ 60 ml/min/1.73m2 for patients with creatinine levels above 2.0 mg/dl.
* Patients must have adequate hepatic function with total bilirubin ≤ 1.5 times the institutional normal value and AST ≤ 2 times the institutional normal value.
* Patient must have no prior or current active autoimmune disease requiring management with immunosuppression. This includes inflammatory bowel disease, systemic vasculitis, scleroderma, psoriasis, hemolytic anemia, immune-mediated thrombocytopenia, rheumatoid arthritis, systemic lupus erythematosus, Sjogren's syndrome, sarcoidosis or other rheumatologic disease. Asthma and chronic obstructive pulmonary disease that does not require daily systemic corticosteroids is acceptable.
* The patient with previous history of malignancy is eligible for this study only if the patient meets the following criteria for cancer survivor:
* (i) patient has undergone potentially curative therapy for all prior malignancies;
* (ii) patient has been considered disease free for at least 5 years.
* For all sexually active patients, the use of adequate barrier contraception (hormonal or barrier method of birth control) will be required during therapy, prior to study entry and for the duration of study participation. Patients must agree to refrain from becoming pregnant 2 years after beginning treatment with IMP321. Non-pregnant status will be determined in all women of childbearing potential.
* After being informed of the treatment involved, patients must give written consent. The patient should not have any serious medical or psychiatric illness that would prevent either the giving of informed consent or the receipt of treatment.
Exclusion Criteria
* Pregnant and nursing women patients are not eligible.
* Patients known to be HIV (patient self-report) positive are ineligible because of the potential inability to modulate immune responses.
* Patients with a QTc of \>460 msec.
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Washington University School of Medicine
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
William G. Hawkins, M.D.
Role: PRINCIPAL_INVESTIGATOR
Washington Univerisity
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Washington University
St Louis, Missouri, United States
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
Storniolo AM, Allerheiligen SR, Pearce HL. Preclinical, pharmacologic, and phase I studies of gemcitabine. Semin Oncol. 1997 Apr;24(2 Suppl 7):S7-2-S7-7.
Green MR. Gemcitabine safety overview. Semin Oncol. 1996 Oct;23(5 Suppl 10):32-5.
Burris HA 3rd, Moore MJ, Andersen J, Green MR, Rothenberg ML, Modiano MR, Cripps MC, Portenoy RK, Storniolo AM, Tarassoff P, Nelson R, Dorr FA, Stephens CD, Von Hoff DD. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol. 1997 Jun;15(6):2403-13. doi: 10.1200/JCO.1997.15.6.2403.
Linehan DC, Goedegebuure PS. CD25+ CD4+ regulatory T-cells in cancer. Immunol Res. 2005;32(1-3):155-68. doi: 10.1385/IR:32:1-3:155.
Liyanage UK, Moore TT, Joo HG, Tanaka Y, Herrmann V, Doherty G, Drebin JA, Strasberg SM, Eberlein TJ, Goedegebuure PS, Linehan DC. Prevalence of regulatory T cells is increased in peripheral blood and tumor microenvironment of patients with pancreas or breast adenocarcinoma. J Immunol. 2002 Sep 1;169(5):2756-61. doi: 10.4049/jimmunol.169.5.2756.
Triebel F. LAG-3: a regulator of T-cell and DC responses and its use in therapeutic vaccination. Trends Immunol. 2003 Dec;24(12):619-22. doi: 10.1016/j.it.2003.10.001.
Buisson S, Triebel F. MHC class II engagement by its ligand LAG-3 (CD223) leads to a distinct pattern of chemokine and chemokine receptor expression by human dendritic cells. Vaccine. 2003 Feb 14;21(9-10):862-8. doi: 10.1016/s0264-410x(02)00533-9.
Andreae S, Buisson S, Triebel F. MHC class II signal transduction in human dendritic cells induced by a natural ligand, the LAG-3 protein (CD223). Blood. 2003 Sep 15;102(6):2130-7. doi: 10.1182/blood-2003-01-0273. Epub 2003 May 29.
El Mir S, Triebel F. A soluble lymphocyte activation gene-3 molecule used as a vaccine adjuvant elicits greater humoral and cellular immune responses to both particulate and soluble antigens. J Immunol. 2000 Jun 1;164(11):5583-9. doi: 10.4049/jimmunol.164.11.5583.
Prigent P, El Mir S, Dreano M, Triebel F. Lymphocyte activation gene-3 induces tumor regression and antitumor immune responses. Eur J Immunol. 1999 Dec;29(12):3867-76. doi: 10.1002/(SICI)1521-4141(199912)29:123.0.CO;2-E.
Cappello P, Triebel F, Iezzi M, Caorsi C, Quaglino E, Lollini PL, Amici A, Di Carlo E, Musiani P, Giovarelli M, Forni G. LAG-3 enables DNA vaccination to persistently prevent mammary carcinogenesis in HER-2/neu transgenic BALB/c mice. Cancer Res. 2003 May 15;63(10):2518-25.
Di Carlo E, Cappello P, Sorrentino C, D'Antuono T, Pellicciotta A, Giovarelli M, Forni G, Musiani P, Triebel F. Immunological mechanisms elicited at the tumour site by lymphocyte activation gene-3 (LAG-3) versus IL-12: sharing a common Th1 anti-tumour immune pathway. J Pathol. 2005 Jan;205(1):82-91. doi: 10.1002/path.1679.
Huard B, Tournier M, Hercend T, Triebel F, Faure F. Lymphocyte-activation gene 3/major histocompatibility complex class II interaction modulates the antigenic response of CD4+ T lymphocytes. Eur J Immunol. 1994 Dec;24(12):3216-21. doi: 10.1002/eji.1830241246.
Hannier S, Tournier M, Bismuth G, Triebel F. CD3/TCR complex-associated lymphocyte activation gene-3 molecules inhibit CD3/TCR signaling. J Immunol. 1998 Oct 15;161(8):4058-65.
Workman CJ, Vignali DA. The CD4-related molecule, LAG-3 (CD223), regulates the expansion of activated T cells. Eur J Immunol. 2003 Apr;33(4):970-9. doi: 10.1002/eji.200323382.
Macon-Lemaitre L, Triebel F. The negative regulatory function of the lymphocyte-activation gene-3 co-receptor (CD223) on human T cells. Immunology. 2005 Jun;115(2):170-8. doi: 10.1111/j.1365-2567.2005.02145.x.
Huang CT, Workman CJ, Flies D, Pan X, Marson AL, Zhou G, Hipkiss EL, Ravi S, Kowalski J, Levitsky HI, Powell JD, Pardoll DM, Drake CG, Vignali DA. Role of LAG-3 in regulatory T cells. Immunity. 2004 Oct;21(4):503-13. doi: 10.1016/j.immuni.2004.08.010.
Workman CJ, Vignali DA. Negative regulation of T cell homeostasis by lymphocyte activation gene-3 (CD223). J Immunol. 2005 Jan 15;174(2):688-95. doi: 10.4049/jimmunol.174.2.688.
Triebel F, Hacene K, Pichon MF. A soluble lymphocyte activation gene-3 (sLAG-3) protein as a prognostic factor in human breast cancer expressing estrogen or progesterone receptors. Cancer Lett. 2006 Apr 8;235(1):147-53. doi: 10.1016/j.canlet.2005.04.015. Epub 2005 Jun 8.
Lienhardt C, Azzurri A, Amedei A, Fielding K, Sillah J, Sow OY, Bah B, Benagiano M, Diallo A, Manetti R, Manneh K, Gustafson P, Bennett S, D'Elios MM, McAdam K, Del Prete G. Active tuberculosis in Africa is associated with reduced Th1 and increased Th2 activity in vivo. Eur J Immunol. 2002 Jun;32(6):1605-13. doi: 10.1002/1521-4141(200206)32:63.0.CO;2-6.
Immutep. 2006. ImmuFact IMP321 Product Information Brochure.
Fougeray S, Brignone C, Triebel F. A soluble LAG-3 protein as an immunopotentiator for therapeutic vaccines: Preclinical evaluation of IMP321. Vaccine. 2006 Jun 29;24(26):5426-33. doi: 10.1016/j.vaccine.2006.03.050. Epub 2006 Mar 31.
Tseng JF, Willett CG, Fernandez-del Castillo C, Ryan DP, Clark JW, Zhu AX, Rattner DW, Winkelmann JL, Warshaw AL. Patients undergoing treatment for pancreatic adenocarcinoma can mount an effective immune response to vaccinations. Pancreatology. 2005;5(1):67-74. doi: 10.1159/000084492. Epub 2005 Mar 15.
Co, E.L.a., Gemcitabine Product Info. 2003.
Series, M.H., 2003. MICROMEDEX, Greenwood Village, Colorado
Hawkins WG, Gold JS, Dyall R, Wolchok JD, Hoos A, Bowne WB, Srinivasan R, Houghton AN, Lewis JJ. Immunization with DNA coding for gp100 results in CD4 T-cell independent antitumor immunity. Surgery. 2000 Aug;128(2):273-80. doi: 10.1067/msy.2000.107421.
Ko K, Yamazaki S, Nakamura K, Nishioka T, Hirota K, Yamaguchi T, Shimizu J, Nomura T, Chiba T, Sakaguchi S. Treatment of advanced tumors with agonistic anti-GITR mAb and its effects on tumor-infiltrating Foxp3+CD25+CD4+ regulatory T cells. J Exp Med. 2005 Oct 3;202(7):885-91. doi: 10.1084/jem.20050940. Epub 2005 Sep 26.
Moore MJ, Goldstein D, Hamm J, Figer A, Hecht JR, Gallinger S, Au HJ, Murawa P, Walde D, Wolff RA, Campos D, Lim R, Ding K, Clark G, Voskoglou-Nomikos T, Ptasynski M, Parulekar W; National Cancer Institute of Canada Clinical Trials Group. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 2007 May 20;25(15):1960-6. doi: 10.1200/JCO.2006.07.9525. Epub 2007 Apr 23.
Related Links
Access external resources that provide additional context or updates about the study.
Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
07-0265
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.