BATS With in Combination With Low Dose IL-1 and GM-CSF for Advanced Pancreatic Cancer

NCT ID: NCT02620865

Last Updated: 2023-05-15

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

2 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-12-31

Study Completion Date

2021-06-21

Brief Summary

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This phase Ib/II trial studies the side effects and best dose of bispecific antibody armed activated T-cells when given together with aldesleukin and sargramostim and to see how well they work in treating patients with pancreatic cancer that has spread from where it started to nearby tissue or lymph nodes (locally advanced) or other places in the body (metastatic). Bispecific antibody armed activated T-cells are the patient's own T cells that are coated with a bispecific antibody comprising 2 antibodies chemically joined together. These antibodies have specific targets and binding properties that may give the T cells a greater ability to seek out, attach to, and kill more cancer cells.

Detailed Description

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PRIMARY OBJECTIVES:

I. Confirm in a single dose phase I (3 to 6 patients \[pts\]) that 8 infusions of 10\^10 epidermal growth factor receptor (EGFR) bispecific antibody armed activated T cells (BATs) given twice per week in combination with interleukin (IL)-2 (aldesleukin) (300,000 IU/m\^2/day) and granulocyte-macrophage colony stimulating factor (GM-CSF) (sargramostim) (250 ug/m\^2/twice weekly) beginning 3 days before the 1st infusion and ending on the day of the last infusion is safe.

II. Perform a phase II clinical trial to estimate the clinical efficacy of 8 infusions of 10\^10 EGFR BATs in combination with IL-2 and GM-CSF in 39 evaluable pts (including the 3-6 pts in the single dose phase I).

SECONDARY OBJECTIVES:

I. Determine if infusions of EGFR BATs significantly increase cellular or humoral anti-pancreatic cancer (PC) responses by peripheral blood mononuclear cells (PBMC) at different time points after last EGFR BATs infusion and if those responses persist beyond 2 months (mos).

II. Obtain original tumor paraffin blocks prior to treatment and evaluate blocks for cluster of differentiation (CD)3, CD4, CD8, programmed cell death (PD)1/programmed cell death ligand (PDL)1, monocytes subpopulations, myeloid-derived suppressor cells (MDSC), and cytoplasmic interferon (IFN)-gamma and IL-10 by immunohistochemical staining to quantitate type and number of tumor infiltrating lymphocytes (TILs) in the tumor microenvironment to estimate whether the type and number correlate with clinical responses.

III. To determine the time to progression (TTP).

OUTLINE: This is a phase Ib, dose-escalation study of anti-CD3 x anti-EGFR-bispecific antibody armed activated T-cells followed by a phase II study.

Patients receive one of the following standard chemotherapy regimens at the discretion of the treating physician: gemcitabine hydrochloride intravenously (IV) over 30 minutes; gemcitabine hydrochloride IV over 30 minutes and paclitaxel albumin-stabilized nanoparticle formulation IV over 30-40 minutes; oxaliplatin IV over 2 hours, fluorouracil IV over 46 hours and leucovorin calcium IV over 2 hours; or fluorouracil IV over 46 hours, leucovorin calcium IV over 2 hours, irinotecan hydrochloride IV, and oxaliplatin IV over 2 hours. Approximately 2 weeks after standard chemotherapy completion, patients receive anti-CD3 x anti-EGFR-bispecific antibody armed activated T-cells IV over 5-30 minutes twice weekly for 4 weeks. Patients also receive aldesleukin subcutaneously (SC) and sargramostim SC on day -3 before the first anti-CD3 x anti-EGFR-bispecific antibody armed activated T-cells infusion and continuing twice weekly until the final infusion.

After completion of study treatment, patients are followed up for 18 months.

Conditions

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Metastatic Pancreatic Adenocarcinoma Recurrent Pancreatic Carcinoma Stage III Pancreatic Cancer Stage IV Pancreatic Cancer

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment (anti-CD3 x anti-EGFR BATs)

Patients receive one of the following standard chemotherapy regimens at the discretion of the treating physician: gemcitabine hydrochloride IV over 30 minutes; gemcitabine hydrochloride IV over 30 minutes and paclitaxel albumin-stabilized nanoparticle formulation IV over 30-40 minutes; oxaliplatin IV over 2 hours, fluorouracil IV over 46 hours and leucovorin calcium IV over 2 hours; or fluorouracil IV over 46 hours, leucovorin calcium IV over 2 hours, irinotecan hydrochloride IV, and oxaliplatin IV over 2 hours. Approximately 2 weeks after standard chemotherapy completion, patients receive anti-CD3 x anti-EGFR-bispecific antibody armed activated T-cells IV over 5-30 minutes twice weekly for 4 weeks. Patients also receive aldesleukin SC and sargramostim SC on day -3 before the first anti-CD3 x anti-EGFR-bispecific antibody armed activated T-cells infusion and continuing twice weekly until the final infusion.

Group Type EXPERIMENTAL

Aldesleukin

Intervention Type BIOLOGICAL

Given SC

Antibody Therapy

Intervention Type BIOLOGICAL

Given anti-CD3 x anti-EGFR-bispecific antibody armed activated T-cells IV

Fluorouracil

Intervention Type DRUG

Given IV

Gemcitabine Hydrochloride

Intervention Type DRUG

Given IV

Irinotecan Hydrochloride

Intervention Type DRUG

Given IV

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Leucovorin Calcium

Intervention Type DRUG

Given IV

Oxaliplatin

Intervention Type DRUG

Given IV

Paclitaxel Albumin-Stabilized Nanoparticle Formulation

Intervention Type DRUG

Given IV

Sargramostim

Intervention Type BIOLOGICAL

Given SC

Interventions

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Aldesleukin

Given SC

Intervention Type BIOLOGICAL

Antibody Therapy

Given anti-CD3 x anti-EGFR-bispecific antibody armed activated T-cells IV

Intervention Type BIOLOGICAL

Fluorouracil

Given IV

Intervention Type DRUG

Gemcitabine Hydrochloride

Given IV

Intervention Type DRUG

Irinotecan Hydrochloride

Given IV

Intervention Type DRUG

Laboratory Biomarker Analysis

Correlative studies

Intervention Type OTHER

Leucovorin Calcium

Given IV

Intervention Type DRUG

Oxaliplatin

Given IV

Intervention Type DRUG

Paclitaxel Albumin-Stabilized Nanoparticle Formulation

Given IV

Intervention Type DRUG

Sargramostim

Given SC

Intervention Type BIOLOGICAL

Other Intervention Names

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125-L-Serine-2-133-interleukin 2 Proleukin r-serHuIL-2 Recombinant Human IL-2 Recombinant Human Interleukin-2 passive antibody therapy 5-Fluoro-2,4(1H, 3H)-pyrimidinedione 5-Fluorouracil 5-Fluracil 5-FU AccuSite Actino-Hermal Adrucil Arumel Cytosafe Efudex Efurix Fiverocil Fluoro Uracil Fluoroplex Fluouracil Flurablastin Fluracedyl Fluracil Fluril Fluroblastin Flurox Ribofluor Ro 2-9757 Ro-2-9757 Timazin dFdCyd Difluorodeoxycytidine Hydrochloride Gemzar LY-188011 Campto Camptosar Camptothecin 11 Camptothecin-11 CPT 11 CPT-11 U-101440E Adinepar Calcifolin Calcium (6S)-Folinate Calcium Folinate Calcium Leucovorin Calfolex Calinat Cehafolin Citofolin Citrec Citrovorum Factor Cromatonbic Folinico Dalisol Disintox Divical Ecofol Emovis Factor, Citrovorum Flynoken A Folaren Folaxin FOLI-cell Foliben Folidan Folidar Folinac Folinate Calcium folinic acid Folinic Acid Calcium Salt Pentahydrate Folinoral Folinvit Foliplus Folix Imo Lederfolat Lederfolin Leucosar leucovorin Rescufolin Rescuvolin Tonofolin Wellcovorin 1-OHP Dacotin Dacplat Diaminocyclohexane Oxalatoplatinum Eloxatin Eloxatine JM-83 Oxalatoplatin Oxalatoplatinum RP 54780 RP-54780 SR-96669 ABI 007 ABI-007 Abraxane Albumin-bound Paclitaxel Albumin-Stabilized Nanoparticle Paclitaxel nab-paclitaxel Nanoparticle Albumin-bound Paclitaxel Nanoparticle Paclitaxel protein-bound paclitaxel 23-L-Leucinecolony-Stimulating Factor 2 DRG-0012 Leukine Prokine rhu GM-CFS Sagramostim Sargramostatin

Eligibility Criteria

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Inclusion Criteria

* Histological or cytological proof of pancreatic adenocarcinoma; must have locally advanced or metastatic pancreatic cancer who have received at least first line chemotherapy and may have responding, stable or progressive disease
* Expected survival \>= 3 months
* Karnofsky performance scale (KPS) \>= 70% or Southwestern Oncology Group (SWOG) performance status 0 or 1
* Absolute neutrophil count (ANC) \>= 1,000/mm\^3
* Lymphocyte count \>= 400/mm\^3
* Platelet count \>= 75,000/mm\^3
* Hemoglobin \>= 8 g/dL
* Serum creatinine \< 2.0 mg/dl, creatinine clearance \>= 50 ml/mm (can be calculated or measured)
* Total bilirubin =\< 2 mg/dl (biliary stent is allowed)
* Serum glutamate pyruvate transaminase (SGPT) and serum glutamic oxaloacetic transaminase (SGOT) \< 5.0 times normal
* Left ventricular ejection fraction (LVEF) \>= 45% at rest (multigated acquisition scan \[MUGA\] or echocardiogram \[Echo\])
* Females of childbearing potential, and males, must be willing to use an effective method of contraception
* Females of childbearing potential must have a negative pregnancy test within 7 days of being registered for protocol therapy

Exclusion Criteria

* Any chemotherapy related toxicities from prior treatment (\> grade 2 per Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v\]4.0)
* Known hypersensitivity to cetuximab or other EGFR antibody
* Treatment with any investigational agent within 14 days prior to being registered for protocol therapy
* Symptomatic brain metastasis
* Chronic treatment with systemic steroids or another immuno-suppressive agent
* Serious non-healing wound, ulcer, bone fracture, major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to being registered for protocol therapy
* Active liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis
* Known human immunodeficiency virus (HIV) infection
* Active bleeding or a pathological condition that is associated with a high risk of bleeding (therapeutic anticoagulation is allowed)
* Has an active infection requiring systemic therapy
* A serious uncontrolled medical disorder that in the opinion of the investigator may be jeopardized by the treatment with protocol therapy
* Females must not be breastfeeding
* Patient (Pt) may be excluded if, in the opinion of the principal investigator (PI) and investigator team, the pt is not capable of being compliant
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Barbara Ann Karmanos Cancer Institute

OTHER

Sponsor Role lead

Responsible Party

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Anthony F. Shields, MD PhD

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Anthony Shields

Role: PRINCIPAL_INVESTIGATOR

Barbara Ann Karmanos Cancer Institute

Locations

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Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status

Countries

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United States

References

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Lum LG, Thakur A, Choi M, Deol A, Kondadasula V, Schalk D, Fields K, Dufrense M, Philip P, Dyson G, Aon HD, Shields AF. Clinical and immune responses to anti-CD3 x anti-EGFR bispecific antibody armed activated T cells (EGFR BATs) in pancreatic cancer patients. Oncoimmunology. 2020 Jun 10;9(1):1773201. doi: 10.1080/2162402X.2020.1773201.

Reference Type DERIVED
PMID: 32939319 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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NCI-2015-01942

Identifier Type: REGISTRY

Identifier Source: secondary_id

2015-100

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA022453

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2015-100

Identifier Type: -

Identifier Source: org_study_id

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