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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2015-01942 | Registry Identifier | CTRP (Clinical Trial Reporting Program) | |
| 2015-100 | Other Identifier | Wayne State University/Karmanos Cancer Institute | |
| P30CA022453 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Aldesleukin | Biological | Given SC |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Biomarker Analysis (Including CD3, CD4, CD8, PD1, PDL1, Monocytes, MDSC, IFN-gamma, IL-10, and TILs) Assessed Using Immunohistochemistry | Each biomarker and computed biomarker will be evaluated for normality and transformed (including non-parametric) if necessary to achieve normality. Summary statistics (including means, medians, and standard deviations) will be produced for each variable and subsequently associate each variable with OS using Cox regression. In addition, a threshold for each variable associating with OS will be defined using classification and regression trees. The tumor will be stained for inflammatory biomarkers. Specifically, T cells with undergo cytoplasmic staining for IFN and IL-10 and the level and ratio of these markers will be evaluated. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Anthony Shields | Barbara Ann Karmanos Cancer Institute | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Wayne State University/Karmanos Cancer Institute | Detroit | Michigan | 48201 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32939319 | Derived | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. Aldesleukin: Given SC Antibody Therapy: Given anti-CD3 x anti-EGFR-bispecific antibody armed activated T-cells IV Fluorouracil: Given IV Gemcitabine Hydrochloride: Given IV Irinotecan Hydrochloride: Given IV Laboratory Biomarker Analysis: Correlative studies Leucovorin Calcium: Given IV Oxaliplatin: Given IV Paclitaxel Albumin-Stabilized Nanoparticle Formulation: Given IV Sargramostim: Given SC |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | May 27, 2016 |
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| Antibody Therapy | Biological | Given anti-CD3 x anti-EGFR-bispecific antibody armed activated T-cells IV |
|
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| Fluorouracil | Drug | Given IV |
|
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| Gemcitabine Hydrochloride | Drug | Given IV |
|
|
| Irinotecan Hydrochloride | Drug | Given IV |
|
|
| Laboratory Biomarker Analysis | Other | Correlative studies |
|
| Leucovorin Calcium | Drug | Given IV |
|
|
| Oxaliplatin | Drug | Given IV |
|
|
| Paclitaxel Albumin-Stabilized Nanoparticle Formulation | Drug | Given IV |
|
|
| Sargramostim | Biological | Given SC |
|
|
| Up to 18 months |
| Incidence of Toxicity (CTCAE Version 4.0) | Toxicity rates will be estimated using all treated patients. | Up to 18 months |
| Progression Free Survival (PFS) | Descriptive statistics (point and exact 90% confidence interval estimates from the resultant Kaplan-Meier curve) will be generated for PFS. The median PFS 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 |
| Quantitative Immune Response | For the quantitative immune response variables, summary statistics (including means, medians, and standard deviations) will be produced pre- and post-BATs treatment. Subsequent analyses will compare the immune response variables (after a suitable transformation, if necessary) pre- and post-treatment using a paired t-test (or Wilcoxon sign ranked test if the data are not approximately normally distributed). To explore whether immune responses associate with clinical responses, the association between the baseline of each biomarker and clinical endpoints (such as response, or OS) will be analyze | Up to 18 months |
| TTP | To explore whether immune responses associate with clinical responses, the association between the baseline of each biomarker and clinical endpoints (such as response, or OS) will be analyzed using logistic regression for binary endpoints and Cox regression for time to event endpoints. | Up to 18 months |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. Aldesleukin: Given SC Antibody Therapy: Given anti-CD3 x anti-EGFR-bispecific antibody armed activated T-cells IV Fluorouracil: Given IV Gemcitabine Hydrochloride: Given IV Irinotecan Hydrochloride: Given IV Laboratory Biomarker Analysis: Correlative studies Leucovorin Calcium: Given IV Oxaliplatin: Given IV Paclitaxel Albumin-Stabilized Nanoparticle Formulation: Given IV Sargramostim: Given SC |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||||||
| Age, Continuous | Mean | Full Range | years |
| |||||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||||
| Region of Enrollment | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Median | 90% Confidence Interval | years | Up to 18 months |
|
|
| ||||||||||||||||||||||||||
| Secondary | Biomarker Analysis (Including CD3, CD4, CD8, PD1, PDL1, Monocytes, MDSC, IFN-gamma, IL-10, and TILs) Assessed Using Immunohistochemistry | Each biomarker and computed biomarker will be evaluated for normality and transformed (including non-parametric) if necessary to achieve normality. Summary statistics (including means, medians, and standard deviations) will be produced for each variable and subsequently associate each variable with OS using Cox regression. In addition, a threshold for each variable associating with OS will be defined using classification and regression trees. The tumor will be stained for inflammatory biomarkers. Specifically, T cells with undergo cytoplasmic staining for IFN and IL-10 and the level and ratio of these markers will be evaluated. | Analysis cannot be performed since data were not collected | Posted | Up to 18 months |
| ||||||||||||||||||||||||||||||
| Secondary | Incidence of Toxicity (CTCAE Version 4.0) | Toxicity rates will be estimated using all treated patients. | Posted | Count of Participants | Participants | Up to 18 months |
| |||||||||||||||||||||||||||||
| Secondary | Progression Free Survival (PFS) | Descriptive statistics (point and exact 90% confidence interval estimates from the resultant Kaplan-Meier curve) will be generated for PFS. The median PFS 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. | Posted | Median | 90% Confidence Interval | Years | Up to 18 months |
| ||||||||||||||||||||||||||||
| Secondary | Quantitative Immune Response | For the quantitative immune response variables, summary statistics (including means, medians, and standard deviations) will be produced pre- and post-BATs treatment. Subsequent analyses will compare the immune response variables (after a suitable transformation, if necessary) pre- and post-treatment using a paired t-test (or Wilcoxon sign ranked test if the data are not approximately normally distributed). To explore whether immune responses associate with clinical responses, the association between the baseline of each biomarker and clinical endpoints (such as response, or OS) will be analyze | Analysis cannot be performed since data were not collected | Posted | Up to 18 months |
| ||||||||||||||||||||||||||||||
| Secondary | TTP | To explore whether immune responses associate with clinical responses, the association between the baseline of each biomarker and clinical endpoints (such as response, or OS) will be analyzed using logistic regression for binary endpoints and Cox regression for time to event endpoints. | Analysis cannot be performed since data were not collected | Posted | Up to 18 months |
|
Adverse event data was collected up to 3 months after off-treatment date, up to 18 months.
The definitions do not differ.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. Aldesleukin: Given SC Antibody Therapy: Given anti-CD3 x anti-EGFR-bispecific antibody armed activated T-cells IV Fluorouracil: Given IV Gemcitabine Hydrochloride: Given IV Irinotecan Hydrochloride: Given IV Laboratory Biomarker Analysis: Correlative studies Leucovorin Calcium: Given IV Oxaliplatin: Given IV Paclitaxel Albumin-Stabilized Nanoparticle Formulation: Given IV Sargramostim: Given SC | 1 | 2 | 0 | 2 | 2 | 2 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anorexia | Gastrointestinal disorders | Systematic Assessment |
| ||
| Anxiety | General disorders | Systematic Assessment |
| ||
| Chills | General disorders | Systematic Assessment |
| ||
| Depression | Psychiatric disorders | Systematic Assessment |
| ||
| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
| ||
| Dizziness | Nervous system disorders | Systematic Assessment |
| ||
| Dry Mouth | Gastrointestinal disorders | Systematic Assessment |
| ||
| Fatigue | General disorders | Systematic Assessment |
| ||
| Fever | General disorders | Systematic Assessment |
| ||
| Gastroesophageal reflux disease | Gastrointestinal disorders | Systematic Assessment |
| ||
| Headache | Nervous system disorders | Systematic Assessment |
| ||
| Myalgia | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Nausea | Gastrointestinal disorders | Systematic Assessment |
| ||
| Rash maculo-papular | Skin and subcutaneous tissue disorders | Systematic Assessment |
| ||
| Vomiting | Gastrointestinal disorders | Systematic Assessment |
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Anthony Shields | Karmanos Cancer Institute | 313-576-8735 | shieldsa@karmanos.org |
| Jul 27, 2022 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D010190 | Pancreatic Neoplasms |
| ID | Term |
|---|---|
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D004701 | Endocrine Gland Neoplasms |
| D004066 | Digestive System Diseases |
| D010182 | Pancreatic Diseases |
| D004700 | Endocrine System Diseases |
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| ID | Term |
|---|---|
| C082598 | aldesleukin |
| D007116 | Immunization, Passive |
| D005472 | Fluorouracil |
| C029917 | dehydroftorafur |
| D000093542 | Gemcitabine |
| D000077146 | Irinotecan |
| D002955 | Leucovorin |
| D000077150 | Oxaliplatin |
| D013660 | Taxes |
| D000068196 | Albumin-Bound Paclitaxel |
| C520255 | 130-nm albumin-bound paclitaxel |
| C081222 | sargramostim |
| D003115 | Colony-Stimulating Factors |
| ID | Term |
|---|---|
| D007114 | Immunization |
| D007167 | Immunotherapy |
| D056747 | Immunomodulation |
| D001691 | Biological Therapy |
| D013812 | Therapeutics |
| D007158 | Immunologic Techniques |
| D008919 | Investigative Techniques |
| D014498 | Uracil |
| D011744 | Pyrimidinones |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D002166 | Camptothecin |
| D000470 | Alkaloids |
| D005575 | Formyltetrahydrofolates |
| D013763 | Tetrahydrofolates |
| D005492 | Folic Acid |
| D011622 | Pterins |
| D011621 | Pteridines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D003067 | Coenzymes |
| D045762 | Enzymes and Coenzymes |
| D056831 | Coordination Complexes |
| D009930 | Organic Chemicals |
| D004467 | Economics |
| D004472 | Health Care Economics and Organizations |
| D017239 | Paclitaxel |
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D004224 | Diterpenes |
| D013729 | Terpenes |
| D000418 | Albumins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D006023 | Glycoproteins |
| D006001 | Glycoconjugates |
| D002241 | Carbohydrates |
| D016298 | Hematopoietic Cell Growth Factors |
| D016207 | Cytokines |
| D036341 | Intercellular Signaling Peptides and Proteins |
| D010455 | Peptides |
| D001685 | Biological Factors |
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| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
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| Units | Counts |
|---|
| Participants |
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