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

NCT02620865 | Completed Phase 1 Results

• 3 other identifiers: 2015-100NCI-2015-01942P30CA022453
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Median Overall Survival (OS)

  Descriptive statistics (point and exact 90% confidence interval estimates from the resultant Kaplan-Meier curve) will be generated for OS. The median OS will be estimated on an intention-to-treat basis (using all registered patients), and on a response-evaluable basis (using all patients who completed all BAT infusions) using the Kaplan-Meier method.

  Up to 18 months

Secondary Outcomes (5)

• Biomarker Analysis (Including CD3, CD4, CD8, PD1, PDL1, Monocytes, MDSC, IFN-gamma, IL-10, and TILs) Assessed Using Immunohistochemistry

  Up to 18 months

• Incidence of Toxicity (CTCAE Version 4.0)

  Up to 18 months

• Progression Free Survival (PFS)

  Up to 18 months

• Quantitative Immune Response

  Up to 18 months

• TTP

  Up to 18 months

Study Arms (1)

Treatment (anti-CD3 x anti-EGFR BATs)

EXPERIMENTAL

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.

Biological: Aldesleukin; Biological: Antibody Therapy; Drug: Fluorouracil; Drug: Gemcitabine Hydrochloride; Drug: Irinotecan Hydrochloride; Other: Laboratory Biomarker Analysis; Drug: Leucovorin Calcium; Drug: Oxaliplatin; Drug: Paclitaxel Albumin-Stabilized Nanoparticle Formulation; Biological: Sargramostim

Interventions

Aldesleukin BIOLOGICAL

Given SC

Also known as: 125-L-Serine-2-133-interleukin 2, Proleukin, r-serHuIL-2, Recombinant Human IL-2, Recombinant Human Interleukin-2

Treatment (anti-CD3 x anti-EGFR BATs)

Antibody Therapy BIOLOGICAL

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

Also known as: passive antibody therapy

Treatment (anti-CD3 x anti-EGFR BATs)

Fluorouracil DRUG

Given IV

Also known as: 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

Treatment (anti-CD3 x anti-EGFR BATs)

Gemcitabine Hydrochloride DRUG

Given IV

Also known as: dFdCyd, Difluorodeoxycytidine Hydrochloride, Gemzar, LY-188011

Treatment (anti-CD3 x anti-EGFR BATs)

Irinotecan Hydrochloride DRUG

Given IV

Also known as: Campto, Camptosar, Camptothecin 11, Camptothecin-11, CPT 11, CPT-11, U-101440E

Treatment (anti-CD3 x anti-EGFR BATs)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (anti-CD3 x anti-EGFR BATs)

Leucovorin Calcium DRUG

Given IV

Also known as: 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

Treatment (anti-CD3 x anti-EGFR BATs)

Oxaliplatin DRUG

Given IV

Also known as: 1-OHP, Dacotin, Dacplat, Diaminocyclohexane Oxalatoplatinum, Eloxatin, Eloxatine, JM-83, Oxalatoplatin, Oxalatoplatinum, RP 54780, RP-54780, SR-96669

Treatment (anti-CD3 x anti-EGFR BATs)

Paclitaxel Albumin-Stabilized Nanoparticle Formulation DRUG

Given IV

Also known as: ABI 007, ABI-007, Abraxane, Albumin-bound Paclitaxel, Albumin-Stabilized Nanoparticle Paclitaxel, nab-paclitaxel, Nanoparticle Albumin-bound Paclitaxel, Nanoparticle Paclitaxel, protein-bound paclitaxel

Treatment (anti-CD3 x anti-EGFR BATs)

Sargramostim BIOLOGICAL

Given SC

Also known as: 23-L-Leucinecolony-Stimulating Factor 2, DRG-0012, Leukine, Prokine, rhu GM-CFS, Sagramostim, Sargramostatin

Treatment (anti-CD3 x anti-EGFR BATs)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Barbara Ann Karmanos Cancer Institute: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Related Publications (1)

• 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.

  PMID: 32939319 DERIVED

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

aldesleukin; Immunization, Passive; Fluorouracil; dehydroftorafur; Gemcitabine; Irinotecan; Leucovorin; Oxaliplatin; Taxes; Albumin-Bound Paclitaxel; 130-nm albumin-bound paclitaxel; sargramostim; Colony-Stimulating Factors

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Immunization; Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Investigative Techniques; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Camptothecin; Alkaloids; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Organic Chemicals; Economics; Health Care Economics and Organizations; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors

Results Point of Contact

• Title: Dr. Anthony Shields
• Organization: Karmanos Cancer Institute

shieldsa@karmanos.org

313-576-8735

Study Officials

• Anthony Shields

  Barbara Ann Karmanos Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 1, 2015
• First Posted: December 3, 2015
• Study Start: December 1, 2015
• Primary Completion: June 21, 2021
• Study Completion: June 21, 2021
• Last Updated: May 15, 2023
• Results First Posted: May 15, 2023

Record last verified: 2023-04

Locations

US (1)