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

NCT03087591 | Completed Phase 1 Results FDA Drug

• 4 other identifiers: IRB00041173NCI-2017-00050CCCWFU 03716P30CA012197
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Clinical Response as Assessed by RECIST

  Up to approximately 4 years

• Frequency of Immune Cells

  Days 15 and 28

• Immune Response as Measured by Interferon Production

  Days 15 and 28

• Neutrophil to Lymphocyte Ratio

  Days 15 and 28

• Overall Survival (OS)

  From the initial infusion to confirmation of death, assessed up to approximately 4 years

Study Arms (1)

Treatment (APN401)

EXPERIMENTAL

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; Biological: siRNA-transfected Peripheral Blood Mononuclear Cells (PBMC) APN401

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (APN401)

siRNA-transfected Peripheral Blood Mononuclear Cells (PBMC) APN401 BIOLOGICAL

Given IV

Also known as: APN401, siRNA-transfected PBMC APN401

Treatment (APN401)

Eligibility Criteria

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

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Wake Forest University Health Sciences: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Comprehensive Cancer Center of Wake Forest University

Winston-Salem, North Carolina, 27157, United States

Location

Related Publications (1)

• 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.

  PMID: 35362047 DERIVED

MeSH Terms

Conditions

Brain Neoplasms; Neoplasm Metastasis; Colorectal Neoplasms; Pancreatic Neoplasms

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases

Results Point of Contact

• Title: Principal Investigator
• Organization: Wake Forest Baptist Comprehensive Cancer Center

ptriozzi@wakehealth.edu

336-716-5772

Study Officials

• Pierre Triozzi

  Wake Forest University Health Sciences

  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: SPONSOR

Study Record Dates

• First Submitted: January 13, 2017
• First Posted: March 22, 2017
• Study Start: April 28, 2017
• Primary Completion: July 31, 2019
• Study Completion: December 8, 2020
• Last Updated: October 10, 2024
• Results First Posted: October 10, 2024

Record last verified: 2024-09

Locations

US (1)