Stage IV Non-small Cell Lung CancerPhase 1NCT04142931
Sequentional Immuno Apheresis Plasma Volume Escalation Cohort Study of Reduction of Soluble Tumor Necrosis Factor Receptors 1 and 2 (sTNFR1/2) With or Without Nivolumab in Patients With Inoperable or Metastatic Solid Tumors
A Phase 1 study testing ImmunicomAIAC in people with Stage IV Non-small Cell Lung Cancer and Stage IV Melanoma, run by Dr. Ronnie Shapira at 1 site in Israel.
Trial summary
Sequential immune apheresis plasma volume escalation cohort study of reduction of soluble Tumor Necrosis Factors Receptors 1/2 (sTNFR1/2), with or without Nivolumab, in patients with inoperable or metastatic solid Tumors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Stage IV Non-small Cell Lung Cancer, Stage IV Melanoma, Triple Negative Breast Cancer
- What is being tested?
- ImmunicomAIAC
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteIsrael
- Study dates
- 24 Feb 2020to 30 Dec 2022
- 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
- ● Signed informed consent
- Age ⩾ 18 years
- Able to comply with study protocol, in the investigator's judgment
- Histologically confirmed diagnosis of locally advanced unresectable, or metastatic (Stage IV) melanoma, triple negative breast cancer, non-small cell lung cancer, renal cell carcinoma
- Progressed on at least one standard of care systemic therapy (e.g., chemotherapy or immunotherapy) in advanced/metastatic disease settings prior to inclusion in this study
- Eastern Cooperative Oncology Group Performance Status of 0 or 1
Show all 27Show fewer
- Measurable disease according to RECIST v1.1
- Life expectancy ⩾ 3 months
- Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 14 days prior to initiation of study treatment:
- ANC ≥ 1.5 x 109/L
- WBC ≥ 1.5 x 109/L
- Lymphocyte count ≥ 0.5 x 109/L
- Platelet count ≥ 100 x 109/L
- Hemoglobin ≥ 10g/dL (may be achieved with transfusion support)
- Serum albumin ≥ 3.2mg/dL
- Total bilirubin ≤ x1.5 ULN
- AST and ALT ≤ x2.5 ULN (in case of liver metastasis up to x5 ULN)
- ALP ≤ 2.5 x ULN (in case of liver or bone metastasis up to x5 ULN)
- Creatinine ≤x2 ULN
- Serum uric acid ≤ x1.5 ULN
- Calcium levels within normal range
- INR≤x1.5 ULN
- Adequate psychological and physical support structure
- Female subjects may be enrolled in the trial if they are:
- ○ Of non-childbearing potential which is defined as: i. ⩾ 45 years of age and has not had menses for greater than 1 year ii. Amenorrhea for ⩾ 2 years without a hysterectomy and oophorectomy and FSH value in the postmenopausal range at screening evaluation iii. State post hysterectomy or oophorectomy or tubal ligation. 2. Of childbearing potential who have a negative pregnancy test result within 14 days prior to initiation of study, and agree to remain abstinent or use a contraceptive method with a failure rate of <1% per year during the treatment period (bilateral tubal ligation, male sterilization, hormone releasing intrauterine device and copper intrauterine device; any hormonal contraceptive method must be supplemented with a barrier method)
- Have provided tissue for biomarker analysis from a newly or recently-obtained biopsy (within 90 days of Study Day 1)
- Willingness to undergo tumor biopsies of accessible lesions during treatment and at progression for exploratory biomarker analysis
Who cannot join
- ● Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigation device within 2 weeks of treatment initiation
- Has received prior chemotherapy, immunotherapy, radioactive or biological cancer therapy within 2 weeks prior to the treatment initiation, or who has not recovered to CTCAE Grade 1 or better from the clinically significant AEs due to cancer therapeutics administered more than 4 weeks prior to treatment initiation, except for stable neurosensory deficits related to chemotherapy and hypothyroidism or type I diabetes due to immunotherapy
- Is expected to require any other form of systemic or localized antineoplastic therapy while in study
- Known history of hematologic malignancy or of another primary solid tumor, unless the subject has undergone potentially curative therapy with no evidence of that disease for five years. The time requirement does not apply to the tumor for which the subject is enrolled in the study or subjects that underwent successful definitive resection of basal or squamous cell carcinoma of the skin, superficial bladder cancer, in situ cervical cancer, in situ breast cancer or other in situ cancers.
- Have refused standard of care therapy CNS criteria
- Actively progressing brain metastasis meaning new or enlarging known lesions.
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- Leptomeningeal metastasis
- Intracranial hemorrhage in the last six months.
- Patients with CNS metastasis will be eligible if:
- All lesions treated with radiotherapy or surgery, and are stable for at least 4 weeks prior to initiation of study treatment, and/or
- Radiographically stable metastasis without local therapy over the last 3 months prior to initiation of study treatment Cardiovascular criteria
- Unstable angina or new-onset angina within 3 months prior to initiation of study
- Symptomatic congestive heart failure defined as NYHA Class III or higher
- Myocardial infarction within 6 months prior to initiation of study
- Clinically significant hypotension, defined as systolic pressure under 90mmHg
- Concurrent therapy with ACE inhibitors
- Significant uncontrolled arrhythmias, with the exception of atrial fibrillation controlled for >30 days prior to initiation of study treatment
- EF<55% Coagulation criteria
- History of deep vein thrombosis or pulmonary embolism in the last 6 month.
- Active or history of hypercoagulability/thrombophilia which is not related to the underlying condition.
- Fibrinogen serum levels >650mg/dL
- Active infection criteria
- Severe systemic infection within 4 weeks prior to initiation of study, including but not limited to, hospitalization or complications of infection, bacteremia, fungemia, infected stents or indwelling devices etc.
- Signs and symptoms of infection within 2 weeks prior to initiation of study
- Positive HIV test
- Active Hepatitis B infection (chronic or acute), defined as a positive HbsAg test at screening. Past or resolved HBV infection, defined as having a negative hepatitis B surface antigen and a positive total hepatitis B core antibody at screening, are eligible
- Active Hepatitis C virus infection, defined as having a positive HCV antibody test and a positive HCV RNA test at screening.
- Treatment with a live attenuated vaccine within 4 weeks prior to initiation of study Other criteria
- Uncorrectable electrolyte abnormalities
- Known hypersensitivity to apheresis
- Current, severe, uncontrolled systemic illness other than cancer, that according to the investigator's judgment should exclude the patient
- Any psychological, familial, sociological or geographical condition that may mapper compliance with the protocol and follow-up after treatment discontinuation
- Pregnant or breastfeeding, or intending to become pregnant during the study
- Known clinically significant liver disease, including alcoholism, cirrhosis or other inherited liver diseases
- Inability to install central line catheter
- Treatment with anti TNF agents - infliximab (Remicade), adalimumab (Humira), certolizumab pegol (Cimzia), and golimumab (Simponi), or etanercept (Enbrel).
- Active autoimmune disease - known or suspected. Hypothyroidism or hypopituitarism adequately treated with supplemental hormones, type 1 diabetes mellitus or skin disorders (vitiligo, psoriasis, alopecia) not requiring systemic immunosuppression are eligible.
- Permanent systemic steroid therapy. Steroid treatment equal or less than 10 mg prednisolone (or equivalent) is allowed.
Trial locations and contacts
1 site in 1 country.
Israel1 site, 1 recruiting
- Recruiting
Sheba Medical Center
Ramat Gan, 5262100
Ronnie Shapira, Dr., ronnie.shapira@sheba.health.gov.il
Meital Bar, 972-3-5305201, meital.bar@sheba.health.gov.il
About this study
Official title: A Pilot Study, Single-Center, Open-Label, Sequentional Immuno Apheresis Plasma Volume Escalation Cohort Study of Reduction of Soluble Tumor Necrosis Factor Receptors 1 and 2 (sTNFR1/2) With or Without Nivolumab in Patients With Inoperable or Metastatic Solid Tumors
Sequential immune apheresis plasma volume escalation cohort study of reduction of soluble Tumor Necrosis Factors Receptors 1/2 (sTNFR1/2), with or without Nivolumab, in patients with inoperable or metastatic solid Tumors. This study evaluates Immunicom fs LW-02 device used with Spectra Optia apheresis system, aiming to answer two different study questions:
- Safety, tolerability and effectiveness of the device.
- Safety, tolerability and effectiveness of the device, employed as monotherapy, or combined with Nivolumab.
Read the detailed description
This is a pilot, single-center, open-label, sequential immune apheresis plasma volume escalation cohort study of reduction of soluble Tumor Necrosis Factors Receptors 1/2 (sTNFR1/2), with or without Nivolumab, in patients with inoperable or metastatic solid Tumors. This study evaluates Immunicom fs LW-02 device used with Spectra Optia apheresis system, aiming to answer two different study questions:
- Safety, tolerability and effectiveness of the device.
- Safety, tolerability and effectiveness of the device, employed as monotherapy, or combined with Nivolumab.
- Conditions
- Stage IV Non-small Cell Lung Cancer, Stage IV Melanoma, Triple Negative Breast Cancer, Renal Cell Carcinoma Stage IV
- Being tested
- ImmunicomAIAC
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Melanoma, Triple Negative Breast Neoplasms, Carcinoma, Renal Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ImmunicomAIACCombination product
Also called Nivolumab
filtration through the ImmunicomAIAC followed by Nivolumab Administrated IV starting C2.
| Study group | Role | What they receive |
|---|---|---|
| filtration of 2X PV | Active comparator | filtration of 2X PV through the ImmunicomAIAC Receives: Combination Product: ImmunicomAIAC |
| filtration of 2X PV combined with Nivolumab 240mg | Active comparator | filtration of 2X PV through the Immunicom AIAC, and nivolumab 240 mg given every 14 days for 4 times. Nivolumab will be initiated in C2. Receives: Combination Product: ImmunicomAIAC |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Treatment-Emergent Adverse Events (Safety) of IA therapy with plasma volume escalation (increase from 2X to 3X plasma volume processed): adverse events
number of patients with adverse events that emerged due to IA
Measured: two years
Incidence of Treatment-Emergent Adverse Events (Safety and tolerability) of IA therapy in combination with nivolumab: adverse events
number of patients with adverse events that emerged due to IA therapy in combination with nivolumab.
Measured: two years
Column efficiency
Changes in sTNFR-1/2 pre and post AIAC column between start and end of every treatment session, and between start and end of every cycle Total capture of sTNF-R1/2 on each column post treatment will be measured using an elution procedure
Measured: two years
Column biochemical effectiveness
The biochemical efficacy will be evaluated throughout the study by measuring the changes of sTNFR-1/2 and TNFα in the plasma in several pre-defined time points - before, during and post every AIAC treatment
Measured: two years
Secondary outcomes (11)
Clinical efficacy: Response Rate (RR) as determined by RECIST v1.1
Response Rate (RR) as determined by RECIST v1.1
Measured: two years
Circulating biomarkers in plasma cytokines Levels
changes in plasma cytokines levels: sTNFR-I (pg/ml), sTNFR-II (pg/ml), TNF (pg/ml), pre and post treatment.
Measured: two years
Circulating biomarkers in peripheral blood mononuclear cells (PBMC)
changes in peripheral blood mononuclear cells (PBMC) phenotypes pre and post treatment
Measured: two years
Duration of response
Duration of response (DoR) as determined by RECIST v1.1
Measured: two years
Clinical benefit rate
Clinical benefit rate (CBR) defined as CR plus PR plus stable disease (SD) ≥6 months
Measured: two years
Progression Free Survival
Progression-Free Survival (PFS) as determined by RECIST v1.1
Measured: two years
Overall Survival
Overall Survival (OS)
Measured: two years
Clinical efficacy by physician evaluation of ECOG status
Eastern Cooperative Oncology Group (ECOG) status (score 0-4)
Measured: two years
Patient reported outcomes by questionnaire EORTC QLQ-C30
Overall quality of life scale: 1 (very poor), 7 (excellent). higher score mean better outcome
Measured: two years
Patient reported outcomes by questionnaire EQ-5D- 5L
patient's health state: 1- 'The best health you can imagine' , 5- 'The worst health you can imagine'. higher score mean worse outcome
Measured: two years
Patient reported outcomes by questionaire Hospital Anxiety and Depression Scale (HADS)
measure anxiety and depression in a general medical population of patients. 0-7 = Normal 8-10 = Borderline abnormal (borderline case) 11-21 = Abnormal (case)
Measured: two years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Oct 2019
- Study start24 Feb 2020
- Primary completion30 Dec 2021 (estimated)
- Study completion30 Dec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Stage IV Non-small Cell Lung CancerStudies of the same condition, open and under way.
- 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
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Dr. Ronnie Shapira
- Sponsor type
- Other government
- Collaborators
- Immunicom Inc. San Diego California, USA
- Responsible party
- Sponsor-investigator, Dr. Ronnie Shapira, Sheba Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04142931
- Sponsor's protocol ID
- SHEBA-19-6136-RS-CTIL
- Status last verified
- Mar 2021
- First submitted
- 13 Oct 2019
- Last updated
- 24 Mar 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study, Single-Center, Open-Label, Sequentional Immuno Apheresis Plasma Volume Escalation Cohort Study of Reduction of Soluble Tumor Necrosis Factor Receptors 1 and 2 (sTNFR1/2) With or Without Nivolumab in Patients With Inoperable or Metastatic Solid Tumors
- ClinicalTrials.gov ID
- NCT04142931
- Acronym / sponsor ID
- SHEBA-19-6136-RS-CTIL
- Conditions
- Stage IV Non-small Cell Lung Cancer, Stage IV Melanoma, Triple Negative Breast Cancer, Renal Cell Carcinoma Stage IV
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Dr. Ronnie ShapiraOther government
- Collaborators
- Immunicom Inc. San Diego California, USA
- Study start
- 24 Feb 2020 (actual)
- Primary completion
- 30 Dec 2021 (estimated)
- Study completion
- 30 Dec 2022 (estimated)
- First posted
- 29 Oct 2019 (actual)
- 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.
Sequential immune apheresis plasma volume escalation cohort study of reduction of soluble Tumor Necrosis Factors Receptors 1/2 (sTNFR1/2), with or without Nivolumab, in patients with inoperable or metastatic solid Tumors. This study evaluates Immunicom fs LW-02 device used with Spectra Optia apheresis system, aiming to answer two different study questions:
- Safety, tolerability and effectiveness of the device.
- Safety, tolerability and effectiveness of the device, employed as monotherapy, or combined with Nivolumab.
Detailed description
This is a pilot, single-center, open-label, sequential immune apheresis plasma volume escalation cohort study of reduction of soluble Tumor Necrosis Factors Receptors 1/2 (sTNFR1/2), with or without Nivolumab, in patients with inoperable or metastatic solid Tumors. This study evaluates Immunicom fs LW-02 device used with Spectra Optia apheresis system, aiming to answer two different study questions:
- Safety, tolerability and effectiveness of the device.
- Safety, tolerability and effectiveness of the device, employed as monotherapy, or combined with Nivolumab.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| filtration of 2X PV | Active comparator | Combination Product: ImmunicomAIACfiltration of 2X PV through the ImmunicomAIAC |
| filtration of 2X PV combined with Nivolumab 240mg | Active comparator | Combination Product: ImmunicomAIACfiltration of 2X PV through the Immunicom AIAC, and nivolumab 240 mg given every 14 days for 4 times. Nivolumab will be initiated in C2. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (27 listed)
- ● Signed informed consent
- ○ Of non-childbearing potential which is defined as: i. ⩾ 45 years of age and has not had menses for greater than 1 year ii. Amenorrhea for ⩾ 2 years without a hysterectomy and oophorectomy and FSH value in the postmenopausal range at screening evaluation iii. State post hysterectomy or oophorectomy or tubal ligation. 2. Of childbearing potential who have a negative pregnancy test result within 14 days prior to initiation of study, and agree to remain abstinent or use a contraceptive method with a failure rate of <1% per year during the treatment period (bilateral tubal ligation, male sterilization, hormone releasing intrauterine device and copper intrauterine device; any hormonal contraceptive method must be supplemented with a barrier method)
Key exclusion criteria (38 listed)
- ● Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigation device within 2 weeks of treatment initiation
- Leptomeningeal metastasis
- Intracranial hemorrhage in the last six months.
- Patients with CNS metastasis will be eligible if:
- All lesions treated with radiotherapy or surgery, and are stable for at least 4 weeks prior to initiation of study treatment, and/or
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 |
|---|---|---|
| ImmunicomAIACAlso: Nivolumabfiltration through the ImmunicomAIAC followed by Nivolumab Administrated IV starting C2. | Combination product | filtration of 2X PV, filtration of 2X PV combined with Nivolumab 240mg |
Primary outcome
Incidence of Treatment-Emergent Adverse Events (Safety) of IA therapy with plasma volume escalation (increase from 2X to 3X plasma volume processed): adverse events
Time frame: two years
number of patients with adverse events that emerged due to IA
Incidence of Treatment-Emergent Adverse Events (Safety and tolerability) of IA therapy in combination with nivolumab: adverse events
Time frame: two years
number of patients with adverse events that emerged due to IA therapy in combination with nivolumab.
Column efficiency
Time frame: two years
Changes in sTNFR-1/2 pre and post AIAC column between start and end of every treatment session, and between start and end of every cycle Total capture of sTNF-R1/2 on each column post treatment will be measured using an elution procedure
Column biochemical effectiveness
Time frame: two years
The biochemical efficacy will be evaluated throughout the study by measuring the changes of sTNFR-1/2 and TNFα in the plasma in several pre-defined time points - before, during and post every AIAC treatment
11 secondary outcomes
Clinical efficacy: Response Rate (RR) as determined by RECIST v1.1
Time frame: two years
Circulating biomarkers in plasma cytokines Levels
Time frame: two years
Circulating biomarkers in peripheral blood mononuclear cells (PBMC)
Time frame: two years
Duration of response
Time frame: two years
Clinical benefit rate
Time frame: two years
Progression Free Survival
Time frame: two years
Overall Survival
Time frame: two years
Clinical efficacy by physician evaluation of ECOG status
Time frame: two years
Patient reported outcomes by questionnaire EORTC QLQ-C30
Time frame: two years
Patient reported outcomes by questionnaire EQ-5D- 5L
Time frame: two years
Patient reported outcomes by questionaire Hospital Anxiety and Depression Scale (HADS)
Time frame: two years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Mar 2021.
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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.
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 ImmunicomAIAC in people with Stage IV Non-small Cell Lung Cancer and Stage IV Melanoma, run by Dr. Ronnie Shapira at 1 site in Israel.
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 27 inclusion and 38 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: status not confirmed, as of the sponsor's last update on 24 Mar 2021. 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 Israel. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Ronnie Shapira, MD (972-3-5308414, ronnie.Shapira@sheba.health.gov.il), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Treatment-Emergent Adverse Events (Safety) of IA therapy with plasma volume escalation (increase from 2X to 3X plasma volume processed): adverse events (time frame: two years). The study lists 4 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 24 Mar 2021.