A Study Comparing Immunopheresis® Alone or In Combination With Chemotherapy Versus Chemotherapy Alone in Treatment of Advanced Breast Cancer Patients

NCT ID: NCT04004910

Last Updated: 2022-03-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE1/PHASE2

Total Enrollment

170 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-05-31

Study Completion Date

2023-07-31

Brief Summary

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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 column in removal of Soluble Tumor Necrosis Factor Receptors (sTNF-Rs) from plasma of patients with advanced, refractory Breast Cancer (BC) and for disease control when employed as monotherapy, or in combination with a low dose chemotherapy. A low dose chemotherapy will serve as control.

Detailed Description

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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 column in removal of sTNF-Rs from plasma of patients with advanced, refractory BC and for disease control when employed as monotherapy, or in combination with a low dose chemotherapy. A low dose chemotherapy will serve as control.

Part A (n=10 evaluable patients): Overall safety, tolerability, and sTNF-R-removal effectiveness of LW-02 device-based immunopheresis monotherapy conducted 3 times per week for 4 weeks in patients with advanced TNBC. This part is already completed.

Part B/Part B Extension (n = up to 30 evaluable patients): Overall safety, tolerability, and sTNF-Rs-removal effectiveness of LW-02 device-based Immunopheresis® 3 times per week for up to 16 weeks combined with low dose chemotherapy in patients with advanced refractory BC..

Part C (3 treatment arms; n=50 patients per treatment arm): Randomized comparison of overall safety, tolerability, and clinical efficacy effectiveness of (i) Immunopheresis® monotherapy with the LW-02 column 3 times per week for 16 weeks, (ii) or Immunopheresis® in combination with low dose chemotherapy, and (iii) plain low dose chemotherapy.

Safety Endpoints

1. Safety and tolerability - incidence of Adverse Device Effects (ADEs), Serious Adverse Device Effects (SADEs) and Unanticipated Serious Adverse Device Effects (USADEs) related to immunopheresis procedure as well as Adverse Events (AE) and Serious Adverse Events (SAEs).
2. Safety endpoints of special interest - incidence of tumor lysis syndrome, and systemic inflammatory response syndrome.
3. Patient-Reported Outcomes to evaluate health status and Quality of Life (QoL) instruments for patients with BC:

* Eastern Cooperative Oncology Group (ECOG) status
* EQ-5D-5L index-based scale
* EORTC: QLQ-BR23 (breast), and QLQ-C30 (general cancer questionnaire)
* 6-minute walk test and BORG dyspnea, fatigue scale and hand grip test
* Nutritional status will be assessed with PG-SGA scale and via laboratory assessments of changes in serum albumin and CRP

Efficacy Endpoints

1. Column efficiency and effectiveness in removal of sTNF-Rs from patient plasma without clinically-meaningful leaching of capture ligand (SC-TNF-α) - change in sTNF-R and TNF-α plasma levels from initiation to the end of each Immunopheresis® procedure, including pre- and post-column measurements, between each treatment, and from baseline to end of a treatment cycle (4 weeks - Part A and B/B-extension, or 16 weeks - Part C).
2. Clinical endpoints - response in tumor burden - progression-free survival (PFS), disease control rate (DCR), objective response rate (ORR), clinical benefit rate (CBR), duration of response (DOR), duration of clinical benefit (DOCB), time-to-progression (TTP) and overall survival (OS). Serial evaluation of tumor burden/tumor growth is assessed according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1).

Conditions

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Advanced Breast Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

A Multicenter, Open-Label, Three-Part Study
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Immunopheresis® - Arm 1

All patients will receive up to 16 weeks of initial treatment as per study arm assignment, which will include up to 48 LW-02 column-based Immunopheresis® treatments over a 4-month period (up to 3 procedures per week) though treatment can be extended based on certain protocol-specfied conditions. Each patient assigned to the treatment with LW-02 column-based Immunopheresis® will require central vascular access for the procedure. This part is alrady completed.

Group Type EXPERIMENTAL

Plasma soluble TNF receptor pulldown

Intervention Type OTHER

The Immunoadsorption affinity column, the LW-02 column, 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.

Immunopheresis® combined with low dose chemotherapy - Arm 2

All patients will receive up to 16 weeks of treatment as per study arm assignment, which will include up to 48 LW-02 column-based Immunopheresis® treatments over a 4-month period (up to 3 procedures per week) though treatment can be extended based on certain protocol-specfied conditions. Each patient will require central vascular access for the procedure. Patients also will receive a low dose chemotherapy regimen administered iv or oraly. Patients treated with combination will be administered their chemotherapy following the first LW-02 column-based Immunopheresis® procedure of each week starting from week 2, assuming first week of study treatment serves as a run-in period confirming good tolerance of Immunopheresis® alone.

Group Type EXPERIMENTAL

Plasma soluble TNF receptor pulldown + chemotherapy

Intervention Type OTHER

The Immunoadsorption affinity column, the LW-02 column, 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 to potentially enhancing the latter's cytotoxic effect.

Chemotherapy - Arm 3

Patients who are assigned chemotherapy arm of the study will be treated with low dose chemotherapy alone. The chemotherapy will be administered intravenously or oraly depending on the regimen used.

Group Type ACTIVE_COMPARATOR

Chemotherapy Drugs, Cancer

Intervention Type DRUG

Low dose chemotherapy will be provided to patient either IV or oraly depending on the regimen used.

Interventions

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Plasma soluble TNF receptor pulldown

The Immunoadsorption affinity column, the LW-02 column, 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.

Intervention Type OTHER

Plasma soluble TNF receptor pulldown + chemotherapy

The Immunoadsorption affinity column, the LW-02 column, 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 to potentially enhancing the latter's cytotoxic effect.

Intervention Type OTHER

Chemotherapy Drugs, Cancer

Low dose chemotherapy will be provided to patient either IV or oraly depending on the regimen used.

Intervention Type DRUG

Eligibility Criteria

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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 BC
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 BC confirmation and verification of BC 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 ≥ 7 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 and others).
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Immunicom Inc

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Adam Ostrowski, MD

Role: STUDY_DIRECTOR

Immunicom Inc

Locations

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Katedra i Klinika Onkologii UJ CM

Krakow, Lesser Poland Voivodeship, Poland

Site Status RECRUITING

Centrum Medyczne INTERCOR Sp. z o.o.

Bydgoszcz, , Poland

Site Status RECRUITING

Klinika Pneumonologii, Onkologii i Alergologii SPSK Nr 4 w Lublinie

Lublin, , Poland

Site Status RECRUITING

Centrum Medyczne Pratia Poznań

Skórzewo, , Poland

Site Status SUSPENDED

Altunizade Acıbadem Hospital

Istanbul, Uskudar, Turkey (Türkiye)

Site Status NOT_YET_RECRUITING

Countries

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Poland Turkey (Türkiye)

Central Contacts

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Adam Ostrowski,MD Medical Director, International - Immunicom, Inc.

Role: CONTACT

+48 606 446610

Robert Segal,MD, FACP Chief Medical Officer - Immunicom, Inc.

Role: CONTACT

+1 2672377576

Facility Contacts

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Prof. Piotr Wysocki, MD, PhD

Role: primary

Alina Wadas

Role: backup

+48 782780374

Prof. Tomasz Nowikiewicz, MD, PhD

Role: primary

Tomasz Jankowski, MD, PhD

Role: primary

+48 602 405 127

Gül Başaran, Prof.Dr.

Role: primary

+902166494542

Belma Kurdoğlu Akgün, Msc, PhD

Role: backup

(0212) 304 44 44 ext. 470

Other Identifiers

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CP7-005

Identifier Type: -

Identifier Source: org_study_id

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