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

NCT04142931 | Unknown Phase 1 DMC

• 1 other identifier: SHEBA-19-6136-RS-CTIL
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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. 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

Outcome Measures

Primary Outcomes (4)

• 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

  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.

  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

  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

  two years

Secondary Outcomes (11)

• Clinical efficacy: Response Rate (RR) as determined by RECIST v1.1

  two years

• Circulating biomarkers in plasma cytokines Levels

  two years

• Circulating biomarkers in peripheral blood mononuclear cells (PBMC)

  two years

• Duration of response

  two years

• Clinical benefit rate

  two years

Study Arms (2)

filtration of 2X PV

ACTIVE COMPARATOR

filtration of 2X PV through the ImmunicomAIAC

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.

Combination Product: ImmunicomAIAC

Interventions

ImmunicomAIAC COMBINATION_PRODUCT

filtration through the ImmunicomAIAC followed by Nivolumab Administrated IV starting C2.

Also known as: Nivolumab

filtration of 2X PV; filtration of 2X PV combined with Nivolumab 240mg

Eligibility Criteria

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

You may qualify if:

• ● 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
• Eastern Cooperative Oncology Group Performance Status of 0 or 1
• 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

You may not qualify if:

• ● 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.
• 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

Sponsors & Collaborators

• Dr. Ronnie Shapira: lead
• Immunicom Inc. San Diego California, USA: collaborator

Study Sites (1)

Sheba Medical Center

Ramat Gan, 5262100, Israel

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Melanoma; Triple Negative Breast Neoplasms; Carcinoma, Renal Cell

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Breast Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Ronnie Shapira, MD

CONTACT

972-3-5308414; ronnie.Shapira@sheba.health.gov.il

Meital Bar

CONTACT

972-3-5305201; meital.bar@sheba.health.gov.il

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 13, 2019
• First Posted: October 29, 2019
• Study Start: February 24, 2020
• Primary Completion: December 30, 2021
• Study Completion: December 30, 2022
• Last Updated: March 24, 2021

Record last verified: 2021-03

Locations

IL (1)