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

Sponsor

Wake Forest University Health Sciences (Other)

Overall Status

Completed

CT.gov ID

NCT03087591

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Arm

43.4

Actual Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Malignant Neoplasm in the Brain Metastatic Solid Neoplasm Recurrent Colorectal Carcinoma Recurrent Pancreatic Carcinoma Recurrent Solid Neoplasm Stage IV Colorectal Cancer Stage IV Pancreatic Cancer Stage IVA Colorectal Cancer Stage IVA Pancreatic Cancer Stage IVB Colorectal Cancer Stage IVB Pancreatic Cancer Unresectable Solid Neoplasm	Other: Laboratory Biomarker Analysis Biological: siRNA-transfected Peripheral Blood Mononuclear Cells APN401	Phase 1

Detailed Description

PRIMARY OBJECTIVES:

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:

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 Design

Study Type:

Interventional

Actual Enrollment :

11 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Safety and Immunologic Activity of Multiple Infusions of APN401

Actual Study Start Date :

Apr 28, 2017

Actual Primary Completion Date :

Jul 31, 2019

Actual Study Completion Date :

Dec 8, 2020

Arms and Interventions

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 APN401 Given IV Other Names: APN401 siRNA-transfected PBMC APN401

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 APN401

Given IV

Other Names:

APN401

siRNA-transfected PBMC APN401

Outcome Measures

Primary Outcome Measures

Incidence of adverse events Common Terminology Criteria for Adverse Events version 4.0 [Up to 1 year]
Will be categorized by organ system and severity, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events

Secondary Outcome Measures

Clinical response as assessed by RECIST [Up to 5 years]
Will be summarized as frequency counts and percentages.
Immune response as measured by frequency of immune cells [Up to 1 year]
Will be summarized as medians and ranges. The effects of treatment will be analyzed using paired t-tests or the non-parametric counterpart.
Immune response as measured by interferon production [Up to 1 year]
Will be summarized as medians and ranges. The effects of treatment will be analyzed using paired t-tests or the non-parametric counterpart.
Immune response as measured by neutrophil to lymphocyte ratio [Up to 1 year]
Will be summarized as medians and ranges. The effects of treatment will be analyzed using paired t-tests or the non-parametric counterpart.
Overall survival (OS) [From the initial infusion to confirmation of progression or death, assessed up to 5 years]
Exploratory survival plots will be estimated using the Kaplan Meier approach and median OS will be estimated if enough events occur.
Progression-free survival (PFS) [From the initial infusion to confirmation of progression or death, assessed up to 5 years]
Exploratory survival plots will be estimated using the Kaplan Meier approach and median PFS will be estimated if enough events occur.
Survival as assessed by RECIST [Up to 5 years]
Will be summarized as frequency counts and percentages.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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