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Immunopheresis Alone or In Combination With Chemotherapy Versus Chemotherapy Alone in Advanced Triple Negative Breast Cancer (TNBC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04004910
Recruitment Status : Recruiting
First Posted : July 2, 2019
Last Update Posted : July 2, 2019
Sponsor:
Information provided by (Responsible Party):
Immunicom Inc

Brief Summary:
This is a multicenter, open-label, Phase 1/ 2 study to evaluate the short-term and longer-term safety, tolerability, and effectiveness of immunopheresis with the LW-02 device in removal of Soluble Tumor Necrosis Factor Receptors (sTNF-Rs) from plasma of patients with advanced, refractory Triple Negative Breast Cancer (TNBC) and for disease control when employed as monotherapy, or in combination with a low dose weekly taxane (paclitaxel) plus carboplatin chemotherapy regimen. A weekly, combination of low dose paclitaxel plus carboplatin (paclitaxel+carboplatin) chemotherapy regimen will serve as control.

Condition or disease Intervention/treatment Phase
Advanced Triple Negative Breast Cancer Other: Plasma soluble TNF receptor pulldown Other: Plasma soluble TNF receptor pulldown + chemotherapy Drug: Chemotherapy Drugs, Cancer Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 170 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: A Multicenter, Open-Label, Three-Part Study
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multicenter, Open-Label, Three-Part Study to Evaluate the Safety and Effectiveness of Immunopheresis With Immunicom's LW-02 Device in Removal of Soluble Tumor Necrosis Factor Receptors (sTNF-Rs) as Well as Clinical Efficacy in Treatment of Patients With Advanced, Refractory Triple Negative Breast Cancer (TNBC) Alone, or in Combination With Low Dose Weekly Paclitaxel Plus Carboplatin Chemotherapy Versus Low Dose Weekly Paclitaxel Plus Carboplatin Chemotherapy.
Actual Study Start Date : May 31, 2019
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : July 31, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: Immunopheresis
All patients will receive up to 16 weeks of initial treatment as per study arm assignment, which will include up to 48 LW-02 device-based immunopheresis treatments over a 4-month period (up to 3 procedures per week). Each patient assigned to the treatment with LW-02 device-based immunopheresis will require central vascular access for the procedure. In general, a cuffed,tunneled dual-lumen catheter will be inserted into a central vein and remain in situ throughout the treatment phase or longer if additional treatments are clinically indicated.Immunopheresis will be performed using the LW-02 device used in-line with the Terumo BCT Spectra Optia Apheresis System® (or alternate centrifugal apheresis device) with a secondary plasma processing system such as the Secondary Processing Device [SPD].
Other: Plasma soluble TNF receptor pulldown

Immunoadsorption affinity column, the LW-02 device, uses a proprietary human recombinant protein, single chain TNF-α ligand, covalently linked to a bead resin, that both enhances the capture efficiency of sTNF-Rs while avoiding complications from column leaching. Reduced sTNF-R plasma levels may lead to objective tumor responses.

In combined treatment arm the immunopheresis procedure is combined with low dose chemotherapy enhancing its cytotoxic effect.


Experimental: Immunopheresis combined with weekly chemotherapy
All patients will receive up to 16 weeks of treatment as per study arm assignment, which will include up to 48 LW-02 device-based immunopheresis treatments over a 4-month period (up to 3 procedures per week). Each patient will require central vascular access for the procedure. Immunopheresis will be performed using the LW-02 device used in-line with the Apheresis System with a secondary plasma processing system. Patients will be treated with immunopheresis combined with iv chemotherapy regimen administered iv on a weekly basis (every 7 days) in doses: 80 mg/m2 of paclitaxel and carboplatin AUC2 (Calvert formula). Patients will be administered their chemotherapy following the last LW-02 device-based immunopheresis procedure of each week. Chemotherapy infusion will follow immunopheresis, but will be initiated not earlier than 90 minutes after completion of the procedure in the absence of any immunopheresis-related side effects (i.e. hypotension).
Other: Plasma soluble TNF receptor pulldown + chemotherapy

The LW02 device comprises an immunoadsorption affinity column, employing a proprietary human recombinant protein, single chain TNF-α ligand, covalently linked to a bead resin, that both enhances the capture efficiency of sTNF-Rs while avoiding complications from column leaching. Reduced sTNF-R plasma levels may lead to objective tumor responses.

In combined treatment arm the immunopheresis procedure is combined with low dose chemotherapy to potentially enhancing its cytotoxic effect.


Active Comparator: Chemotherapy
Patients who are assigned chemotherapy arm of the study will be treated with paclitaxel+carboplatin chemotherapy alone. The chemotherapy regimen will be administered intravenously on a weekly basis (every 7 days) in doses: 80 mg/m2 of paclitaxel and carboplatin AUC2 (Calvert formula).
Drug: Chemotherapy Drugs, Cancer
IV chemotherapy with paclitaxel and carboplatin in low doses on a weekly basis.
Other Name: Paclitaxel + carboplatin in low doses




Primary Outcome Measures :
  1. Soluble Tumor Necrosis Factor Receptor (sTNFR) concentrations in plasma (picogram per mL) [ Time Frame: 16 weeks ]
    Change in sTNFR plasma concentrations (reduction in levels at 16 weeks from baseline)

  2. Safety and Tolerability Assessment [ Time Frame: 16 weeks ]
    Safety and tolerability assessment based on adverse event / serious adverse event (AE / SAE) and adverse device / serious adverse device effects (ADE / SADE) reporting using CTCAE/MedDRA coding terms

  3. Quality-of-life (QoL) Assessment [ Time Frame: 16 weeks ]
    QoL measured by EQ-5D-5L index as well as ECOG status


Secondary Outcome Measures :
  1. Tumor burden [ Time Frame: screening (-4-0 weeks), week 8, and week 16, and then every 12 weeks (+/- 1 week) up to one-year follow-up. ]
    Clinical Efficacy Assessment will be based tumor measurements assessed in accordance to RECIST 1.1 criteria.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Signed Informed Consent Form
  2. Age ≥ 18 years female
  3. Able to comply with the study protocol in the investigator's judgment
  4. Histologically confirmed diagnosis of TNBC
  5. Inoperable locally-advanced or metastatic disease
  6. Must be able to provide archival pathological material from primary or metastatic site (formalin-fixed paraffin embedded [FPPE] tissue block) for central TNBC confirmation and verification of TNBC subtype and tmTNF expression
  7. Weight ≥ 35 kg
  8. Life expectancy of at least 3 months with malignancy; expected to live for one year without malignancy.
  9. Adequate organ function:

    1. Hemoglobin ≥ 9.5g/dL (may be achieved with transfusion support)
    2. Absolute Granulocyte Count (ANC) ≥1.5 × 109/L (without granulocyte colony- stimulating factor support within 2 weeks prior to the first study treatment)
    3. Platelets (PTL) ≥ 100 × 109/L
    4. AST/ALT ≤2.5× ULN (patients with documented liver metastases: AST and/or ALT ≤ 5 × ULN; patients with documented liver or bone metastases: alkaline phosphatase ≤ 5 ×ULN)
    5. Serum creatinine (S-Cr) ≤ 1.5
    6. Albumin ≥ LLN
    7. Bilirubin ≤ 1.5 ULN
    8. International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN. This applies only to patients who are not receiving therapeutic anticoagulation agents.
    9. Patients receiving therapeutic anticoagulation agents must be on a stable dose
    10. Calcium level within normal ranges.
  10. The last dose of prior systemic anticancer therapy must have been administered ≥ 21 days prior to study treatment initiation
  11. Measurable disease, as defined by RECIST v1.1
  12. ECOG performance status 0, 1 or 2.
  13. Patients with asymptomatic CNS metastases (treated or untreated), as determined by CT or MRI evaluation during screening and prior radiographic evaluation, are eligible.
  14. For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use double barrier contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 6 months after the last dose of chemotherapy.
  15. Patients must have recovered (i.e., improvement to Grade 1 or better) from all acute toxicities from previous therapy, excluding alopecia. If a patient was previously treated with taxanes, the patient must have recovered from any adverse effects or remain at an acceptable level for patient (i.e. peripheral neuropathy).

Exclusion Criteria:

  1. Symptomatic CNS metastases
  2. Subjects with brain metastases at screening must have clinically controlled neurologic symptoms and have received previous adequate treatment, defined as surgical excision and/or radiation therapy with stable neurologic function and no evidence of CNS disease progression as determined by comparing a computed tomography (CT) scan or magnetic resonance imaging (MRI) scan performed during screening to a prior scan performed at least 4 weeks earlier and provided that the subject is asymptomatic, has no evidence of cavitation or hemorrhage, and does not require corticosteroids;
  3. Leptomeningeal disease
  4. Uncontrolled pericardial effusion or ascites requiring recurrent drainage procedures
  5. Pregnant or lactating or intending to become pregnant during the study - women who are not postmenopausal (postmenopausal defined as ≥ 12 months of non-drug-induced amenorrhea) or surgically sterile must have a negative serum pregnancy test result within 2 weeks prior to initiation of study treatment
  6. Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol, including significant liver disease (such as cirrhosis, uncontrolled major seizure disorder, or superior vena cava syndrome)
  7. Significant cardiovascular disease, such as New York Heart Association cardiac disease ≥ Class III, myocardial infarction within 3 months, unstable arrhythmias, or unstable angina
  8. Patients with known coronary artery disease or left ventricular ejection fraction < 50% must be on a stable medical regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist if appropriate
  9. Patient with known persistent, uncontrolled hypotension
  10. Significant renal disorder requiring dialysis or indication for renal transplant
  11. Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to study treatment initiation
  12. Major surgical procedure within 4 weeks prior to study treatment initiation or anticipation of need for a major surgical procedure during the course of the study other than for diagnosis
  13. Fever, or any active immunosuppressive systemic infection including history of human immunodeficiency virus (HIV) infection
  14. Other serious diseases (e.g., life expectancy less than 3 months) including active second malignancy except for basal cell carcinoma or cervical carcinoma in situ
  15. Active infection
  16. Patients in whom vascular access is not considered achievable
  17. Use of any standard high dose or low dose chemotherapy or immunosuppressive therapies and or standard radiation therapy concurrently as well anticipated need for any of the former during the study
  18. Body mass index (BMI) ≥ 35 kg/m2
  19. Any condition that the patient's physician determines to be detrimental to the patient participating in this study; including any clinically important deviations from normal clinical laboratory values or concurrent medical events.
  20. Inability to understand the local language for use of the patient QOL instruments (EQ-5D-5L).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04004910


Contacts
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Contact: Emel Guldogan Director of Clinical Trials, Immunicom Inc +1 972 358 9087 emel.guldogan@immunicom.com
Contact: Amir Jafri CEO, Immunicom Inc +1 858 353 8747 amir.jafri@immunicom.com

Locations
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Poland
Katedra i Klinika Onkologii UJ CM Recruiting
Kraków, Małopolskie, Poland, 31-531
Contact: Prof. Piotr Wysocki, MD, PhD    +48(12)4248912    klinikaonkologii@su.krakow.pl ; onko@cm-uj.krakow.pl   
Contact: Alina Wadas    +48 782780374      
Principal Investigator: Prof. Piotr Wysocki, MD, PhD         
Sponsors and Collaborators
Immunicom Inc
Investigators
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Study Director: Adam Ostrowski, MD Medical Director Immunicom Inc
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Responsible Party: Immunicom Inc
ClinicalTrials.gov Identifier: NCT04004910    
Other Study ID Numbers: CP7-005
First Posted: July 2, 2019    Key Record Dates
Last Update Posted: July 2, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Immunicom Inc:
Triple Negative Breast Cancer
TNBC
Additional relevant MeSH terms:
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Breast Neoplasms
Triple Negative Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Carboplatin
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action