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Trial record 55 of 157 for:    eribulin

M7824 and Eribulin Mesylate in Treating Participants With Metastatic Triple Negative Breast Cancer

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ClinicalTrials.gov Identifier: NCT03579472
Recruitment Status : Recruiting
First Posted : July 6, 2018
Last Update Posted : October 8, 2018
Sponsor:
Collaborator:
EMD Serono
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:

The goal of this clinical research study is to find the highest tolerable dose of M7824 (MSB0011359C) that can be given with eribulin to patients with triple negative breast cancer (TNBC) that is metastatic (has spread). The safety of this drug combination will also be studied.

This is an investigational study. M7824 is not FDA approved or commercially available. It is currently being used for research purposes only. Eribulin is FDA approved and commercially available for the treatment of breast cancer. The study doctor can explain how the study drugs are designed to work.

Up to 20 participants will be enrolled at MD Anderson. All will take part at MD Anderson.


Condition or disease Intervention/treatment Phase
Anatomic Stage IV Breast Cancer AJCC v8 Estrogen Receptor Negative HER2/Neu Negative Progesterone Receptor Negative Prognostic Stage IV Breast Cancer AJCC v8 Triple-Negative Breast Carcinoma Drug: Anti-PD-L1/TGFbetaRII Fusion Protein M7824 Drug: Eribulin Mesylate Phase 1

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase Ib Trial of M7824 and Eribulin in Patients With Metastatic Triple Negative Breast Cancer (TNBC)
Actual Study Start Date : May 30, 2018
Estimated Primary Completion Date : October 31, 2019
Estimated Study Completion Date : October 31, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: Treatment (M7824, eribulin mesylate)
Participants receive anti-PD-L1/TGFbetaRII fusion protein M7824 IV over 50-80 minutes on days 1, 15, and 29, and eribulin mesylate IV over 2-5 minutes on days 1, 8, 22, and 29. Treatment repeats every 42 days for up to 1 year in the absence of disease progression or unacceptable toxicity.
Drug: Anti-PD-L1/TGFbetaRII Fusion Protein M7824
Given IV
Other Names:
  • Anti-PDL1/TGFb Trap MSB0011359C
  • M7824
  • MSB0011359C

Drug: Eribulin Mesylate
Given IV
Other Names:
  • B1939 Mesylate
  • E7389
  • ER-086526
  • Halaven
  • Halichondrin B Analog




Primary Outcome Measures :
  1. Recommended phase II dose (RP2D) defined as highest dose with dose limiting toxicity (DLT) rate =< 30% [ Time Frame: Up to 90 days post-treatment ]
  2. Incidence of adverse events (AE) [ Time Frame: Up to 90 days post-treatment ]
    AEs tabulated using frequencies and percentages, by severity, by grade, and by relationship to study treatment.



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

Inclusion Criteria:

  1. Signed written informed consent.
  2. Histologically confirmed metastatic triple negative breast cancer with measureable disease by RECIST 1.1 criteria HR defined as positive for the purposes of this study, if expression of estrogen receptor (ER) and/or progesterone receptor (PR) expression is greater than 10% by immunohistochemistry (IHC) and HER2 negative or non-amplified is determined by the current ASCO-CAP criteria, which are as follows: HER2 testing by IHC as 0 or 1+. If HER2 is 2+, ISH (in situ hybridization) must be performed.
  3. ECOG performance status of 0-1.
  4. Baseline MUGA or echocardiogram scans with LVEF of > 50%.
  5. Patient must have adequate organ function as determined by the following lab values: ANC =/> 1500 cells/µL -WBC counts > 2500/µL - Lymphocyte count =/> 300/µL Platelet count =/> 100,000/µL Hemoglobin =/> 9.0 g/dL -Hepatic impairment Child-Pugh<B7 -Total bilirubin </= 1.5 x ULN with the following exception: Patients with known Gilbert disease who have serum indirect bilirubin level </=3 X ULN may be enrolled. Eribulin dose modification necessary in patients with hepatic insufficiency according to USPI - AST and ALT </= 3.0 x ULN with the following exception: Patients with liver involvement: AST and/or ALT </= 5 x ULN - Alkaline phosphatase </= 2.5 x ULN with the following exception: Patients with documented liver involvement or bone metastases: alkaline phosphatase </= 5 x ULN - Creatinine clearance =/> 50 mL/min on the basis of the Cockcroft-Gault glomerular filtration rate estimation: (140 - age) x (weight in kg) x (0.85 if female) 72 x (serum creatinine in mg/dL)
  6. INR and aPTT </= 1.5 x ULN This applies only to patients who do not receive therapeutic anticoagulation; patients receiving therapeutic anticoagulation (such as low-molecular-weight heparin or warfarin) should be on a stable dose.
  7. Men or women 18 years of age or older.
  8. Women of childbearing potential must be using an adequate method of contraception to avoid pregnancy during the study and for at least 4 months after the last dose of study drugs in such a manner that the risk of pregnancy is minimized. Men on study also must be using contraception. Women of childbearing potential (WOCBP) are women who have not been postmenopausal greater than 1 year or undergone a hysterectomy or bilateral oophorectomy.
  9. Negative serum or urine pregnancy test for women within 72 hours of receiving the first dose of the study medication for women of childbearing potential.
  10. Has received no more than 5 previous lines of chemotherapy.

Exclusion Criteria:

  1. Women who are pregnant or breast-feeding.
  2. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti- Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways) for metastatic breast cancer-or- if patient has had prior immune-oncology therapies in the neoadjuvant or adjuvant setting within the past 12 months.
  3. Has had major surgery within 21 days before Cycle 1, Day 1.
  4. Uncontrolled inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis).
  5. Myocardial infarction within 6 months before starting therapy, symptomatic congestive heart failure (New York Heart Association > class II), unstable angina, or unstable cardiac arrhythmia requiring medication.
  6. Serious intercurrent infections or non-malignant medical illness that are uncontrolled or the control of which may be jeopardized by this therapy.
  7. Psychiatric disorders or other conditions rendering the subject incapable of complying with the requirements of the protocols.
  8. History or risk of autoimmune disease, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Bell's palsy, Guillain-Barré syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis.
  9. Patients with a history of autoimmune hypothyroidism (such as atrophic thyroiditis) on a stable dose of thyroid replacement hormone may be eligible.
  10. Patients with uncontrolled Type 1 diabetes mellitus. If on a stable insulin regimen may be eligible, after discussion with Principal Investigator.
  11. Patients with eczema, psoriasis, lichen simplex chronicus of vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided that they meet the following conditions: Patients with psoriasis must have a baseline ophthalmologic exam to rule out ocular manifestations Rash must cover less than 10% of body surface area (BSA) Disease is well controlled at baseline and only requiring low potency topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, fluocinolone 0.01%, desonide 0.05%, alclometasone dipropionate 0.05%) No acute exacerbations of underlying condition within the last 12 months (not requiring psoralen plus ultraviolet A radiation [PUVA], methotrexate, retinoids, biologic agents, oral calcineurin inhibitors; high potency or oral steroids)
  12. Patients with HIV-1 may be eligible if they meet the following conditions: -CD4 cell count > 350 cells/mm3 obtained within 90 days prior to study start -Plasma HIV-1 RNA below detected limit obtained by FDA-approved assays for > 2 years on cART -Plasma HIV-1 RNA level of less than 40 copies/mL obtained by the Abbott m2000 assay or less than 20 copies/mL by Roche Taqman v2.0 assay within 90 days prior to study start -Plasma HIV-1 RNA greater than or equal to 0.4 copies/mL by single copy assay within 120 days prior to entry -Receiving a stable cART regimen containing at least 3 agents (not including ritonavir if less than a 200 mg total daily dose) with no change in the components of antiretroviral therapy for at least 90 days prior to study entry
  13. Patients with prior allogeneic stem cell or solid organ transplantation.
  14. History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest CT scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
  15. Patients with known active hepatitis B (defined as having a positive hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C. Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen [anti HBc] antibody test) are eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
  16. Known active tuberculosis
  17. Administration of a live, attenuated vaccine within 4 weeks before Cycle 1, Day 1 or anticipation that such a live, attenuated vaccine will be required during the study. Influenza vaccination should be given during influenza season only (approximately October to March). Patients must not receive live, attenuated influenza vaccine (e.g., FluMist) within 4 weeks prior to Cycle 1, Day 1 or at any time during the study.
  18. Treatment with systemic immunostimulatory agents (including but not limited to interferons or IL-2) within 4 weeks or five half-lives of the drug, whichever is shorter, from Cycle 1 Day 1.
  19. Treatment with systemic corticosteroids or other systemic immunosuppressive medications (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [TNF] agents) within 1 week prior to Cycle 1 Day 1, or anticipated requirement for systemic immunosuppressive medications during the trial. Patients who have received acute, low dose, systemic immunosuppressant medications (e.g., dexamethasone prior to the anthracycline-based chemotherapy for nausea) may be enrolled in the study. The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) is allowed.
  20. Concurrent disease or condition that would interfere with study participation or safety, such as any of the following: Active, clinically significant infection either grade > 2 by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 or requiring the use of parenteral anti-microbial agents within 14 days before Day 1 of study drug -Clinically significant bleeding diathesis or coagulopathy, including known platelet function disorders Non-healing wound, ulcer, or bone fracture
  21. Known hypersensitivity to any of the components of M7824 or eribulin
  22. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins.
  23. Subjects with active central nervous system (CNS) metastases causing clinical symptoms or metastases that require therapeutic intervention, including leptomeningeal disease, are excluded. Subjects with a history of treated CNS metastases (by surgery or radiation therapy) are not eligible unless they have fully recovered from treatment, demonstrated no progression for at least 2 months, and do not require continued steroid therapy.

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): NCT03579472


Contacts
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Contact: Jennifer K. Litton 713-792-2817 jlitton@mdanderson.org

Locations
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United States, Texas
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Jennifer K. Litton    713-792-2817    jlitton@mdanderson.org   
Principal Investigator: Jennifer K. Litton         
Sponsors and Collaborators
M.D. Anderson Cancer Center
EMD Serono
Investigators
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Principal Investigator: Jennifer Litton M.D. Anderson Cancer Center

Additional Information:
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT03579472     History of Changes
Other Study ID Numbers: 2017-0500
NCI-2018-01140 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
First Posted: July 6, 2018    Key Record Dates
Last Update Posted: October 8, 2018
Last Verified: October 2018

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Breast Neoplasms
Triple Negative Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Halichondrin B
Myeloma Proteins
Paraproteins
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs