Recurrent MelanomaPhase 1NCT02166255
APN401 in Treating Patients With Melanoma, Kidney Cancer, Pancreatic Cancer, or Other Solid Tumors That Are Metastatic or Cannot Be Removed By Surgery
A Phase 1 study testing siRNA-transfected peripheral blood mononuclear cells APN401 and laboratory biomarker analysis in people with Recurrent Melanoma and Recurrent Pancreatic Cancer, 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 small interfering ribonucleic acid (siRNA)-transfected peripheral blood mononuclear cells APN401 (APN401) in treating patients with melanoma, kidney, or pancreatic cancer, or other solid tumors that have spread to other parts of the body or that cannot be… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Recurrent Melanoma, Recurrent Pancreatic Cancer, Recurrent Renal Cell Cancer
- What is being tested?
- siRNA-transfected peripheral blood mononuclear cells APN401 and laboratory biomarker analysis
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2014to May 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- Histologically confirmed metastatic or inoperable solid tumors that are no longer responding to standard therapies; preference will be made to patients with melanoma, renal cell, and pancreatic 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
- Must be at least 4 weeks since treatment with chemotherapy, biochemotherapy, immunotherapy, and/or radiation 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 (WBC) >= 3000/uL
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- 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 prior to randomization 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 12 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: interleukin (IL)-2, interferon, ipilimumab 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 enrolment; 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 > 38.2º 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: A Phase 1, Open-Label, Dose-Ranging Study to Assess the Safety and Immunologic Activity of APN401
This phase I trial studies the side effects and best dose of small interfering ribonucleic acid (siRNA)-transfected peripheral blood mononuclear cells APN401 (APN401) in treating patients with melanoma, kidney, or pancreatic cancer, or other solid tumors that have spread to other parts of the body or that cannot be removed by surgery. There are factors in immune cells in the blood that inhibit their ability to kill cancers. Treating white blood cells with one of these factors in the laboratory may help the white blood cells kill more cancer cells when they are put back in the body.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the toxicities and establish the maximal tolerated dose (MTD) of APN401.
II. To determine the effects of APN401 on immune response.
SECONDARY OBJECTIVES:
- To document clinical response and survival.
OUTLINE: This is a dose-escalation study.
Patients receive autologous siRNA-transfected peripheral blood mononuclear cells APN401 intravenously (IV) over 30 minutes for 1 course in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 2 years, and then annually for 1 year.
- Conditions
- Recurrent Melanoma, Recurrent Pancreatic Cancer, Recurrent Renal Cell Cancer, Stage III Pancreatic Cancer, Stage III Renal Cell Cancer, Stage IIIA Melanoma
- Being tested
- siRNA-transfected peripheral blood mononuclear cells APN401, laboratory biomarker analysis
- Medical subject headings
- Melanoma, Pancreatic Neoplasms, Carcinoma, Renal Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
siRNA-transfected peripheral blood mononuclear cells APN401Biological
Also called APN401
Given IV
laboratory biomarker analysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (APN401) | Experimental | Patients receive autologous siRNA-transfected peripheral blood mononuclear cells APN401 IV over 30 minutes. Receives: Biological: siRNA-transfected peripheral blood mononuclear cells APN401; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose of siRNA-transfected peripheral blood mononuclear cells APN401, defined as the dose in which the number of patients with dose limiting toxicity is less than or equal to one out of six
Measured: 14 days
Incidence of adverse events of APN401, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
Adverse events will be categorized by organ system and severity and summarized as frequency counts and percentages.
Measured: Up to 2 years
Immune response, measured by change in blood Th1-associated cytokines production in response to anti-CD3/28 stimulation or >= tumor antigens post-therapy
Summarized as medians and ranges. The effects of treatment on these markers individually will be analyzed using paired t-tests (possibly after transformation, e.g., logarithmic) or the non-parametric counterpart. Differences between dose levels at particular time points will be analyzed using analysis of variance and 2-sample t-tests, and differences over time will be analyzed using longitudinal methods such as repeated measures. The association between the markers (baseline and changes) and objective response will also be examined.
Measured: Baseline to week 9
Clinical response assessed by RECIST
Summarized as frequency counts and percentages.
Measured: Up to 5 years
Progression-free survival
Standard survival analysis techniques using Kaplan Meier methods will be used.
Measured: From the initial infusion to confirmation of progression or death, assessed up to 5 years
Overall survival
Standard survival analysis techniques using Kaplan Meier methods will be used.
Measured: From the initial infusion to confirmation of progression or death, assessed up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jun 2014 (estimated)
- Study startDec 2014
- Primary completionMay 2016
- Study completionMay 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Recurrent MelanomaStudies 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
- 17 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
- NCT02166255
- Sponsor's protocol ID
- IRB00027911
- Other IDs
- NCI-2014-01234, CCCWFU 99114, P30CA012197
- Status last verified
- Jul 2018
- First submitted
- 16 Jun 2014
- Last updated
- 3 Jul 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Open-Label, Dose-Ranging Study to Assess the Safety and Immunologic Activity of APN401
- ClinicalTrials.gov ID
- NCT02166255
- Acronym / sponsor ID
- IRB00027911
- Conditions
- Recurrent Melanoma, Recurrent Pancreatic Cancer, Recurrent Renal Cell Cancer, Stage III Pancreatic Cancer, Stage III Renal Cell Cancer, Stage IIIA Melanoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Wake Forest University Health SciencesUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Dec 2014 (actual)
- Primary completion
- May 2016 (actual)
- Study completion
- May 2016 (actual)
- First posted
- 18 Jun 2014 (estimated)
- Results
- Not posted in the source record
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 small interfering ribonucleic acid (siRNA)-transfected peripheral blood mononuclear cells APN401 (APN401) in treating patients with melanoma, kidney, or pancreatic cancer, or other solid tumors that have spread to other parts of the body or that cannot be removed by surgery. There are factors in immune cells in the blood that inhibit their ability to kill cancers. Treating white blood cells with one of these factors in the laboratory may help the white blood cells kill more cancer cells when they are put back in the body.
Detailed description
PRIMARY OBJECTIVES:
- To determine the toxicities and establish the maximal tolerated dose (MTD) of APN401.
II. To determine the effects of APN401 on immune response.
SECONDARY OBJECTIVES:
- To document clinical response and survival.
OUTLINE: This is a dose-escalation study.
Patients receive autologous siRNA-transfected peripheral blood mononuclear cells APN401 intravenously (IV) over 30 minutes for 1 course in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 2 years, and then annually for 1 year.
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 | Biological: siRNA-transfected peripheral blood mononuclear cells APN401, Other: laboratory biomarker analysisPatients receive autologous siRNA-transfected peripheral blood mononuclear cells APN401 IV over 30 minutes. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Histologically confirmed metastatic or inoperable solid tumors that are no longer responding to standard therapies; preference will be made to patients with melanoma, renal cell, and pancreatic 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
- Must be at least 4 weeks since treatment with chemotherapy, biochemotherapy, immunotherapy, and/or radiation 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
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 prior to randomization 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 12 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: interleukin (IL)-2, interferon, ipilimumab 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 |
|---|---|---|
| siRNA-transfected peripheral blood mononuclear cells APN401Also: APN401Given IV | Biological | Treatment (APN401) |
| laboratory biomarker analysisCorrelative studies | Other | Treatment (APN401) |
Primary outcome
Maximum tolerated dose of siRNA-transfected peripheral blood mononuclear cells APN401, defined as the dose in which the number of patients with dose limiting toxicity is less than or equal to one out of six
Time frame: 14 days
Incidence of adverse events of APN401, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
Time frame: Up to 2 years
Adverse events will be categorized by organ system and severity and summarized as frequency counts and percentages.
Immune response, measured by change in blood Th1-associated cytokines production in response to anti-CD3/28 stimulation or >= tumor antigens post-therapy
Time frame: Baseline to week 9
Summarized as medians and ranges. The effects of treatment on these markers individually will be analyzed using paired t-tests (possibly after transformation, e.g., logarithmic) or the non-parametric counterpart. Differences between dose levels at particular time points will be analyzed using analysis of variance and 2-sample t-tests, and differences over time will be analyzed using longitudinal methods such as repeated measures. The association between the markers (baseline and changes) and objective response will also be examined.
Clinical response assessed by RECIST
Time frame: Up to 5 years
Summarized as frequency counts and percentages.
Progression-free survival
Time frame: From the initial infusion to confirmation of progression or death, assessed up to 5 years
Standard survival analysis techniques using Kaplan Meier methods will be used.
Overall survival
Time frame: From the initial infusion to confirmation of progression or death, assessed up to 5 years
Standard survival analysis techniques using Kaplan Meier methods will be used.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jul 2018.
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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 siRNA-transfected peripheral blood mononuclear cells APN401 and laboratory biomarker analysis in people with Recurrent Melanoma and Recurrent Pancreatic Cancer, 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 13 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 3 Jul 2018. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Maximum tolerated dose of siRNA-transfected peripheral blood mononuclear cells APN401, defined as the dose in which the number of patients with dose limiting toxicity is less than or equal to one out of six (time frame: 14 days). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 3 Jul 2018; AzTrials last refreshed its copy on 8 Nov 2026.