Metastatic Malignant Neoplasm in the BrainPhase 1NCT03087591
APN401 in Treating Patients With Recurrent or Metastatic Pancreatic Cancer, Colorectal Cancer, or Other Solid Tumors That Cannot Be Removed by Surgery
A Phase 1 study testing Laboratory Biomarker Analysis and siRNA-transfected Peripheral Blood Mononuclear Cells (PBMC) APN401 in people with Metastatic Malignant Neoplasm in the Brain and Metastatic Solid Neoplasm, run by Wake Forest University Health Sciences at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Malignant Neoplasm in the Brain, Metastatic Solid Neoplasm, Recurrent Colorectal Carcinoma
- What is being tested?
- Laboratory Biomarker Analysis and siRNA-transfected Peripheral Blood Mononuclear Cells (PBMC) APN401
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Apr 2017to 8 Dec 2020
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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
Who cannot join
- 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)
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Comprehensive Cancer Center of Wake Forest University
Winston-Salem, North Carolina, 27157
About this study
Official title: 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.
Read the 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.
- Conditions
- Metastatic Malignant Neoplasm in the Brain, Metastatic Solid Neoplasm, Recurrent Colorectal Carcinoma, Recurrent Pancreatic Carcinoma, Recurrent Solid Neoplasm, Stage IV Colorectal Cancer
- Being tested
- Laboratory Biomarker Analysis, siRNA-transfected Peripheral Blood Mononuclear Cells (PBMC) APN401
- Medical subject headings
- Brain Neoplasms, Neoplasm Metastasis, Colorectal Neoplasms, Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Laboratory Biomarker AnalysisOther
Correlative studies
siRNA-transfected Peripheral Blood Mononuclear Cells (PBMC) APN401Biological
Also called APN401, siRNA-transfected PBMC APN401
Given IV
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Other: Laboratory Biomarker Analysis; Biological: siRNA-transfected Peripheral Blood Mononuclear Cells (PBMC) APN401 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Up to 1 year
Secondary outcomes (6)
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
Measured: Up to approximately 4 years
Frequency of Immune Cells
Immune response as measured by frequency of immune cells
Measured: Days 15 and 28
Immune Response as Measured by Interferon Production
Immune response as measured by interferon production
Measured: Days 15 and 28
Neutrophil to Lymphocyte Ratio
Immune response as measured by neutrophil to lymphocyte ratio
Measured: 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.
Measured: 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.
Measured: From the initial infusion to confirmation of progression or death, assessed up to approximately 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Mar 2017
- Study start28 Apr 2017
- Primary completion31 Jul 2019
- Study completion8 Dec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metastatic Malignant Neoplasm in the BrainStudies of the same condition, open and under way.
- More trials run by Wake Forest University Health SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wake Forest University Health Sciences
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Pierre Triozzi, Principal investigator, Wake Forest University Health Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03087591
- Sponsor's protocol ID
- IRB00041173
- Other IDs
- NCI-2017-00050, CCCWFU 03716, P30CA012197
- Status last verified
- Sep 2024
- First submitted
- 13 Jan 2017
- Last updated
- 10 Oct 2024
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
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.
PubMed 35362047
Study at a glance
From the registry record, last updated by the sponsor on 10 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Immunologic Activity of Multiple Infusions of APN401
- ClinicalTrials.gov ID
- NCT03087591
- Acronym / sponsor ID
- IRB00041173
- Conditions
- Metastatic Malignant Neoplasm in the Brain, Metastatic Solid Neoplasm, Recurrent Colorectal Carcinoma, Recurrent Pancreatic Carcinoma, Recurrent Solid Neoplasm, Stage IV Colorectal Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Wake Forest University Health SciencesUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 28 Apr 2017 (actual)
- Primary completion
- 31 Jul 2019 (actual)
- Study completion
- 8 Dec 2020 (actual)
- First posted
- 22 Mar 2017 (actual)
- Results
- Posted 10 Oct 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (APN401) | Experimental | Other: Laboratory Biomarker Analysis, Biological: siRNA-transfected Peripheral Blood Mononuclear Cells (PBMC) APN401Patients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Patients with histologically confirmed inoperable, recurrent or metastatic malignant solid tumors, deemed incurable, and who have either:
- 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
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Laboratory Biomarker AnalysisCorrelative studies | Other | Treatment (APN401) |
| siRNA-transfected Peripheral Blood Mononuclear Cells (PBMC) APN401Also: APN401, siRNA-transfected PBMC APN401Given IV | Biological | Treatment (APN401) |
Primary outcome
Number of Adverse Events Common Terminology Criteria for Adverse Events Version 4.0
Time frame: 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. 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
6 secondary outcomes
Clinical Response as Assessed by RECIST
Time frame: Up to approximately 4 years
Frequency of Immune Cells
Time frame: Days 15 and 28
Immune Response as Measured by Interferon Production
Time frame: Days 15 and 28
Neutrophil to Lymphocyte Ratio
Time frame: Days 15 and 28
Overall Survival (OS)
Time frame: From the initial infusion to confirmation of death, assessed up to approximately 4 years
Progression-free Survival (PFS)
Time frame: From the initial infusion to confirmation of progression or death, assessed up to approximately 4 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Oct 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35362047Wolf 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pierre Triozzi principal investigator
Wake Forest University Health Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Laboratory Biomarker Analysis and siRNA-transfected Peripheral Blood Mononuclear Cells (PBMC) APN401 in people with Metastatic Malignant Neoplasm in the Brain and Metastatic Solid Neoplasm, run by Wake Forest University Health Sciences at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Oct 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Adverse Events Common Terminology Criteria for Adverse Events Version 4.0 (time frame: Up to 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03087591, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Oct 2024.