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

NCT04004910 | Unknown Phase 1 DMC

• 1 other identifier: CP7-005
• Study Type: interventional
• Target: 170
• Locations: 2 countries
• Sites: 5

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 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.

Conditions

Advanced Breast Cancer

Keywords

Advanced Breast Cancer; Breast Cancer; Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (6)

• Soluble Tumor Necrosis Factor Receptor (sTNFR) concentrations in plasma (picogram per mL)

  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, or 16 weeks - Part C).

  16 weeks

• Safety and Tolerability Assessment

  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

  16 weeks

• Safety endpoints of special interest assessment

  Incidence of tumor lysis syndrome and systemic inflammatory response syndrome.

  16 weeks

• Clinical endpoint - overall survival

  A series of secondary efficacy outcome measures will be evaluated based on overall survival from the date of the firststudy treatment and changes in objective response using RECIST (1.1) or iRECIST criteria. The assessed parameterswill be:Overall Survival (OS). Overall survival ( OS ) is defined as the time from randomization to death from any cause, is adirect measure of clinical benefit to a patient.

  16 weeks

• Clinical endpoint - progression free survival

  A series of secondary efficacy outcome measures will be evaluated based on overall survival from the date of the firststudy treatment and changes in objective response using RECIST (1.1) or iRECIST criteria. The assessed parameterswill be:Progression Free Survival (PFS) Progression-free survival ( pfs ) is defined as time from randomization until firstevidence of tumour progression or until death from any cause, whichever comes first.

  16 weeks

• Clinical endpoint - disease control rate

  A series of secondary efficacy outcome measures will be evaluated based on overall survival from the date of the firststudy treatment and changes in objective response using RECIST (1.1) or iRECIST criteria. The assessed parameterswill be:Disease Control Rate (DCR) Overall response rate (ORR) is defined as the proportion of patients who have a partialor complete response to therapy; it does not include stable disease and is a direct measure of drug tumoricidal activity.In contrast, disease control rate is a composite of ORR and stable disease and is useful to measure the efficacy oftherapies that have tumoristatic effects rather than tumoricidal effects.

  16 weeks

Secondary Outcomes (7)

• Nutritional status

  16 weeks

• Patient functioninig with Eastern Cooperative Oncology Group (ECOG)

  16 weeks

• Quality-of-life (QoL) Assessment with EQ-5D-5L scale

  16 weeks

• Quality-of-life (QoL) Assessment with EORTC-QLQ-C30 scale

  16 weeks

• Quality-of-life (QoL) Assessment with EORTC: QLQ-BR23

  16 weeks

Study Arms (3)

Immunopheresis® - Arm 1

EXPERIMENTAL

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.

Other: Plasma soluble TNF receptor pulldown

Immunopheresis® combined with low dose chemotherapy - Arm 2

EXPERIMENTAL

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.

Other: Plasma soluble TNF receptor pulldown + chemotherapy

Chemotherapy - Arm 3

ACTIVE COMPARATOR

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.

Drug: Chemotherapy Drugs, Cancer

Interventions

Plasma soluble TNF receptor pulldown 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® - Arm 1

Plasma soluble TNF receptor pulldown + chemotherapy 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.

Immunopheresis® combined with low dose chemotherapy - Arm 2

Chemotherapy Drugs, Cancer DRUG

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

Chemotherapy - Arm 3

Eligibility Criteria

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

You may qualify if:

• Signed Informed Consent Form
• Age ≥ 18 years female
• Able to comply with the study protocol in the investigator's judgment
• Histologically confirmed diagnosis of BC
• Inoperable locally-advanced or metastatic disease
• 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
• Weight ≥ 35 kg
• Life expectancy of at least 3 months with malignancy; expected to live for one year without malignancy.
• Adequate organ function:
• Hemoglobin ≥ 9.5g/dL (may be achieved with transfusion support)
• Absolute Granulocyte Count (ANC) ≥1.5 × 109/L (without granulocyte colony- stimulating factor support within 2 weeks prior to the first study treatment)
• Platelets (PTL) ≥ 100 × 109/L
• 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)
• Serum creatinine (S-Cr) ≤ 1.5
• Albumin ≥ LLN

You may not qualify if:

• Symptomatic CNS metastases
• 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;
• Leptomeningeal disease
• Uncontrolled pericardial effusion or ascites requiring recurrent drainage procedures
• 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
• 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)
• Significant cardiovascular disease, such as New York Heart Association cardiac disease ≥ Class III, myocardial infarction within 3 months, unstable arrhythmias, or unstable angina
• 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
• Patient with known persistent, uncontrolled hypotension
• Significant renal disorder requiring dialysis or indication for renal transplant
• Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to study treatment initiation
• 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
• Fever, or any active immunosuppressive systemic infection including history of human immunodeficiency virus (HIV) infection
• 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
• Active infection

Sponsors & Collaborators

• Immunicom Inc: lead

Study Sites (5)

Katedra i Klinika Onkologii UJ CM

Krakow, Lesser Poland Voivodeship, 30-688, Poland

RECRUITING

Centrum Medyczne INTERCOR Sp. z o.o.

Bydgoszcz, 85-605, Poland

RECRUITING

Klinika Pneumonologii, Onkologii i Alergologii SPSK Nr 4 w Lublinie

Lublin, 20-954, Poland

RECRUITING

Centrum Medyczne Pratia Poznań

Skórzewo, 60-185, Poland

SUSPENDED

Altunizade Acıbadem Hospital

Istanbul, Uskudar, 34662, Turkey (Türkiye)

NOT YET RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Drug Therapy; Antineoplastic Agents

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Adam Ostrowski, MD

  Immunicom Inc

  STUDY DIRECTOR

Central Study Contacts

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

CONTACT

+48 606 446610; adam.ostrowski@immunicom.com

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

CONTACT

+1 2672377576; robert.segal@immunicom.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: A Multicenter, Open-Label, Three-Part Study

Study Record Dates

• First Submitted: June 24, 2019
• First Posted: July 2, 2019
• Study Start: May 31, 2019
• Primary Completion: December 31, 2022
• Study Completion: July 31, 2023
• Last Updated: March 24, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

TU (1); PL (4)