APN401 in Treating Patients With Recurrent or Metastatic Pancreatic Cancer, Colorectal Cancer, or Other Solid Tumors That Cannot Be Removed by Surgery

Safety and Immunologic Activity of Multiple Infusions of APN401

This phase I trial studies the side effects and best dose of APN401 in treating patients with pancreatic cancer, colorectal cancer, or other solid tumors that have spread to other places in the body or have come back. APN401 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Study Overview

• Status: Completed
• Conditions: Recurrent Pancreatic Carcinoma; Stage IV Pancreatic Cancer; Recurrent Colorectal Carcinoma; Unresectable Solid Neoplasm; Metastatic Malignant Neoplasm in the Brain; Metastatic Solid Neoplasm; Recurrent Solid Neoplasm; Stage IV Colorectal Cancer; Stage IVA Colorectal Cancer; Stage IVA Pancreatic Cancer; Stage IVB Colorectal Cancer; Stage IVB Pancreatic Cancer
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Biological: siRNA-transfected Peripheral Blood Mononuclear Cells (PBMC) APN401

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the toxicities and establish the safety of multiple infusions of small interfering ribonucleic acid (siRNA)-transfected peripheral blood mononuclear cells APN401 (APN401).

SECONDARY OBJECTIVES:

I. To determine the immunologic effects of multiple infusions of APN401. II. To document clinical response and survival.

OUTLINE:

Patients receive siRNA-transfected peripheral blood mononuclear cells APN401 intravenously (IV) over 30 minutes on days 1, 29, and 57 in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 5 years.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Comprehensive Cancer Center of Wake Forest University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with histologically confirmed inoperable, recurrent or metastatic malignant solid tumors, deemed incurable, and who have either:

  • Failed to respond to standard therapy or
  • For whom no standard therapy is available or
  • Refuse to receive standard therapies
• The study is intended to enroll patients with pancreatic and colorectal cancer; patients with other types of solid tumors will require approval by the principal investigator
• Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST)
• Patients with treated, stable, and asymptomatic brain metastases are eligible
• Patients on every 3 or every 4 week systemic therapy programs must be at least 4 weeks since treatment and recovered from any clinically significant toxicity experienced; patients on weekly or daily systemic therapy programs and patients receiving radiation must be at least 1 week since treatment and recovered from any clinically significant toxicity experienced; must be at least 4 weeks and have recovered from major surgery
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• White blood cells >= 3000/uL
• Platelets >= 100,000/uL
• Hematocrit >= 28%
• Creatinine =< 1.6 mg/dL
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 x upper limit of normal
• Bilirubin =< 1.6 mg/dL (except patients with Gilbert's syndrome, who must have a total bilirubin less than 3.0 mg/dL)
• Albumin >= 3.0 g/dL
• International normalized ratio (INR) =< 1.5

Exclusion Criteria:

• Women must not be pregnant or breastfeeding; all women of childbearing potential must have a blood test within 72 hours to rule out pregnancy; women of childbearing potential and sexually active males must be strongly advised to use an accepted and effective method of contraception; women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for 26 weeks after the last dose of investigational product, in such a manner that the risk of pregnancy is minimized; sexually mature females who have not undergone a hysterectomy or who have not been postmenopausal naturally for at least 24 consecutive months (i.e., who have had menses at some time in the preceding 24 consecutive months) are considered to be of childbearing potential; women who are using oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or are practicing abstinence or where their partner is sterile (e.g., vasectomy) should be considered to be of childbearing potential
• Untreated, progressing, or symptomatic brain metastases
• Autoimmune disease, as follows: patients with a history of inflammatory bowel disease are excluded as are patients with a history of symptomatic disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [e.g., Wegener's granulomatosis]); patients with motor neuropathy considered of autoimmune origin (e.g., Guillain-Barre syndrome and myasthenia gravis) are excluded; patients with a history of autoimmune thyroiditis are eligible if their current thyroid disorder is treated and stable with replacement or other medical therapy
• Any other malignancy from which the patient has been disease-free for less than 2 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix
• Other ongoing systemic therapy for cancer, including any other experimental treatment; these include concomitant therapy with any of the following: IL-2, interferon, ipilimumab, pembrolizumab, nivolumab, or other immunotherapy; cytotoxic chemotherapy; and targeted therapies
• Ongoing requirement for an immunosuppressive treatment, including the use of glucocorticoids or cyclosporine, or with a history of chronic use of any such medication within the last 4 weeks before enrollment; patients are excluded if they have any concurrent medical condition that requires the use of systemic steroids (the use of inhaled or topical steroids is permitted)
• Infection with human immunodeficiency virus (HIV)
• Active infection with hepatitis B; active or chronic infection with hepatitis C
• Clinically significant pulmonary dysfunction, as determined by medical history and physical examination; patients with a history of pulmonary dysfunction must have pulmonary function tests with a forced expiratory volume in 1 second (FEV1) >= 60% of predicted and a diffusing capacity of the lung for carbon monoxide (DLCO) >= 55% (corrected for hemoglobin)
• Clinically significant cardiovascular abnormalities (e.g., congestive heart failure or symptoms of coronary artery disease), as determined by medical history and physical examination; patients with a history of cardiac disease must have a normal cardiac stress test (treadmill, echocardiogram, or myocardial perfusion scan) within the past 6 months of study entry
• Active infections or oral temperature > 38.2 degrees Celsius (C) within 48 hours of study entry
• Systemic infection requiring chronic maintenance or suppressive therapy
• Patients are excluded for any underlying medical or psychiatric condition, which in the opinion of the investigator, will make treatment hazardous or obscure the interpretation of adverse events, such as a condition associated with frequent rashes or diarrhea

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (APN401); Patients receive siRNA-transfected peripheral blood mononuclear cells APN401 IV over 30 minutes on days 1, 29, and 57 in the absence of disease progression or unacceptable toxicity.	Other: Laboratory Biomarker Analysis; Correlative studies; Biological: siRNA-transfected Peripheral Blood Mononuclear Cells (PBMC) APN401; Given IV; Other Names: APN401; siRNA-transfected PBMC APN401

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Adverse Events Common Terminology Criteria for Adverse Events Version 4.0	Will be categorized by organ system and severity, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events. Related treatment emergent adverse events by maximum severity. Unexpected grade 4 and all grade 5 events are considered severe adverse events. CTCAE grades 3-5 allergic reactions related to study cell infusion CTCAE grades 3 and greater autoimmune reactions other than that vitiligo CTCAE grades 3 and greater organ toxicity (cardiac, dermatologic, gastrointestinal, hepatic, pulmonary, renal/genitourinary or neurologic) not pre-existing or due to the underlying malignancy and occurring within 30 days of study product infusion	Up to 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Response as Assessed by RECIST	Will be summarized as frequency counts and percentages. RECIST criteria: Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD; Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started	Up to approximately 4 years
Frequency of Immune Cells	Immune response as measured by frequency of immune cells	Days 15 and 28
Immune Response as Measured by Interferon Production	Immune response as measured by interferon production	Days 15 and 28
Neutrophil to Lymphocyte Ratio	Immune response as measured by neutrophil to lymphocyte ratio	Days 15 and 28
Overall Survival (OS)	Exploratory survival plots will be estimated using the Kaplan Meier approach and median overall survival will be estimated if enough events occur.	From the initial infusion to confirmation of death, assessed up to approximately 4 years
Progression-free Survival (PFS)	Exploratory survival plots will be estimated using the Kaplan Meier approach and median PFS will be estimated if enough events occur.	From the initial infusion to confirmation of progression or death, assessed up to approximately 4 years

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Pierre Triozzi, Wake Forest University Health Sciences

Publications and helpful links

General Publications

• Wolf D, Baier G. IFNgamma Helps CBLB-Deficient CD8+ T Cells to Put Up Resistance to Tregs. Cancer Immunol Res. 2022 Apr 1;10(4):370. doi: 10.1158/2326-6066.CIR-22-0080.

Study record dates

Study Major Dates

• Study Start (Actual): April 28, 2017
• Primary Completion (Actual): July 31, 2019
• Study Completion (Actual): December 8, 2020

Study Registration Dates

• First Submitted: January 13, 2017
• First Submitted That Met QC Criteria: March 16, 2017
• First Posted (Actual): March 22, 2017

Study Record Updates

• Last Update Posted (Actual): October 10, 2024
• Last Update Submitted That Met QC Criteria: September 17, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms by Histologic Type; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Disease Attributes; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Endocrine Gland Neoplasms; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Pancreatic Diseases; Neoplasms; Carcinoma; Colorectal Neoplasms; Recurrence; Pancreatic Neoplasms
• Other Study ID Numbers: IRB00041173; P30CA012197 (U.S. NIH Grant/Contract); NCI-2017-00050 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); CCCWFU 03716 (Other Identifier: Comprehensive Cancer Center of Wake Forest University)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No