L-NMMA Plus Taxane Chemotherapy in Refractory Locally Advanced or Metastatic Triple Negative Breast Cancer Patients
NCT ID: NCT02834403
Last Updated: 2023-12-15
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE1/PHASE2
37 participants
INTERVENTIONAL
2016-11-30
2021-01-31
Brief Summary
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Detailed Description
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Conditions
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Keywords
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Study Design
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NON_RANDOMIZED
SEQUENTIAL
TREATMENT
NONE
Study Groups
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L-NMMA 7.5 mg/kg and Docetaxel 75 mg/m2
Phase Ib: L-NMMA and docetaxel will be given for 6 21-day cycles. L-NMMA at doses of 7.5 mg/kg (starting dose) will be administered IV on Days 1-5. Docetaxel will be administered at 75 mg/m2 as an IV 15 min after L-NMMA infusion Day 1.
L-NMMA
Nitric oxide synthase inhibitor
Docetaxel
Mitotic inhibitor, cytotoxic
Amlodipine
Long-acting calcium channel blocker
Pegfilgrastim
Colony-stimulating factor
Enteric-coated aspirin
non-steroidal anti-inflammatory drug
L-NMMA 10 mg/kg and Docetaxel 75 mg/m2
Phase Ib: L-NMMA and docetaxel will be given for 6 21-day cycles. L-NMMA at doses of 10 mg/kg will be administered IV on Days 1-5. Docetaxel will be administered at 75 mg/m2 as an IV 15 min after L-NMMA infusion Day 1.
L-NMMA
Nitric oxide synthase inhibitor
Docetaxel
Mitotic inhibitor, cytotoxic
Amlodipine
Long-acting calcium channel blocker
Pegfilgrastim
Colony-stimulating factor
Enteric-coated aspirin
non-steroidal anti-inflammatory drug
L-NMMA 12.5 mg/kg and Docetaxel 75 mg/m2
Phase Ib: L-NMMA and docetaxel will be given for 6 21-day cycles. L-NMMA at doses of 12.5 mg/kg will be administered IV on Days 1-5. Docetaxel will be administered at 75 mg/m2 as an IV 15 min after L-NMMA infusion Day 1.
L-NMMA
Nitric oxide synthase inhibitor
Docetaxel
Mitotic inhibitor, cytotoxic
Amlodipine
Long-acting calcium channel blocker
Pegfilgrastim
Colony-stimulating factor
Enteric-coated aspirin
non-steroidal anti-inflammatory drug
L-NMMA 15 mg/kg and Docetaxel 75 mg/m2
Phase Ib: L-NMMA and docetaxel will be given for 6 21-day cycles. L-NMMA at doses of 15 mg/kg will be administered IV on Days 1-5. Docetaxel will be administered at 75 mg/m2 as an IV 15 min after L-NMMA infusion Day 1.
L-NMMA
Nitric oxide synthase inhibitor
Docetaxel
Mitotic inhibitor, cytotoxic
Amlodipine
Long-acting calcium channel blocker
Pegfilgrastim
Colony-stimulating factor
Enteric-coated aspirin
non-steroidal anti-inflammatory drug
L-NMMA 17.5 mg/kg and Docetaxel 100 mg/m2
Phase Ib: L-NMMA and docetaxel will be given for 6 21-day cycles. L-NMMA at doses of 17.5 mg/kg will be administered IV on Days 1-5. Docetaxel will be administered at 100 mg/m2 as an IV 15 min after L-NMMA infusion Day 1.
L-NMMA
Nitric oxide synthase inhibitor
Docetaxel
Mitotic inhibitor, cytotoxic
Amlodipine
Long-acting calcium channel blocker
Pegfilgrastim
Colony-stimulating factor
Enteric-coated aspirin
non-steroidal anti-inflammatory drug
L-NMMA 20 mg/kg and Docetaxel 100 mg/m2
Phase Ib: L-NMMA and docetaxel will be given for 6 21-day cycles. L-NMMA at doses of 20 mg/kg will be administered IV on Days 1-5. Docetaxel will be administered at 100 mg/m2 as an IV 15 min after L-NMMA infusion Day 1.
L-NMMA
Nitric oxide synthase inhibitor
Docetaxel
Mitotic inhibitor, cytotoxic
Amlodipine
Long-acting calcium channel blocker
Pegfilgrastim
Colony-stimulating factor
Enteric-coated aspirin
non-steroidal anti-inflammatory drug
Phase II: RP2D determined in the Phase Ib
Phase II: L-NMMA starting dose will be the RP2D determined in the Phase Ib portion of the study.
L-NMMA
Nitric oxide synthase inhibitor
Docetaxel
Mitotic inhibitor, cytotoxic
Amlodipine
Long-acting calcium channel blocker
Pegfilgrastim
Colony-stimulating factor
Enteric-coated aspirin
non-steroidal anti-inflammatory drug
Interventions
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L-NMMA
Nitric oxide synthase inhibitor
Docetaxel
Mitotic inhibitor, cytotoxic
Amlodipine
Long-acting calcium channel blocker
Pegfilgrastim
Colony-stimulating factor
Enteric-coated aspirin
non-steroidal anti-inflammatory drug
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
• Female patients with pathologically determined advanced (progressive disease or refractory to 3 cycles of standard chemotherapy) or metastatic (any line) triple negative breast cancer (TNBC). TNBC is defined as: Estrogen receptor negative and progesterone receptor negative (\<10% staining by immunohistochemistry \[IHC\]).
Human epidermal growth factor receptor 2 (HER2) negative. HER2 negativity must be confirmed by one of the following:
* Fluorescence in situ hybridization (FISH)-negative (FISH ratio \<2), or
* IHC 0-1+, or
* IHC 2+ AND FISH-negative (FISH ratio \<2). Eastern Cooperative Oncology Group performance status of ≤ 2
* Age ≥ 18 years
* Laboratory values within the following ranges:
* Hemoglobin ≥9.0 g/dL (transfusions permitted)
* Absolute neutrophil count ≥1500/mm3 (1.5 x 109/L)
* Platelet count ≥100,000/mm3 (100 x 109/L)
* Total bilirubin \<2 X upper limit of normal (ULN)
* Creatinine (Cr) \<2 X ULN and Cr clearance (CrCl) ≥30 by Cockcroft and Gault
* Alanine transaminase (ALT) and aspartate transaminase (AST) \<2 X ULN (if liver metastases are present then ALT and AST must be \<5 X ULN)
* Have adequate organ function (cardiac ejection fraction of ≥ 45%)
* Negative serum pregnancy test within 7 days of the administration of the first treatment dose for women of childbearing potential (WOCBP). For WOCBP, adequate contraception must be used throughout the study.
* Ability to understand the requirements of the study, provide written informed consent and authorization of use and disclosure of protected health information, and agree to abide by the study restrictions and return for the required assessments.
* Patient must be willing to undergo biopsies as required by the study protocol. Biopsies will be based on acceptable clinical risks as judged by investigator. Tissue from a previous biopsy will be accepted in the form of tissue slides.
Exclusion Criteria
* Patients with metastatic disease who have received radiation therapy, chemotherapy, or non-cytotoxic investigational agents within 2 weeks of study treatment initiation.
* Patients who received docetaxel at any line of treatment within the past 12 months
* Evidence of New York Heart Association class III or greater cardiac disease
* History of myocardial infarction, stroke, ventricular arrhythmia, or symptomatic conduction abnormality within the past 12 months
* History of congenital QT prolongation
* Absolute corrected QT interval of \>480 msec in the presence of potassium \>4.0 milliequivalent/L and magnesium \>1.8 mg/dL
* Any medical or psychiatric condition that would prevent informed consent or limit expected survival to less than 4 weeks
* Symptomatic central nervous system metastases
* Pregnant or nursing women
* Hypersensitivity or intolerance to L-NMMA, docetaxel, amlodipine, pegfilgrastim, or their components
* Use of amlodipine or another calcium channel blocker in the past 14 days
* Alcoholism or hepatic disease with the exception of liver metastases
* Severe renal insufficiency (CrCl \<30 mL/min \[Cockcroft and Gault\])
* History of gastrointestinal bleeding, ulceration, or perforation
* Concurrent use of potent cytochrome P450 (CYP)3A4 inhibitors
* Concurrent use of potent CYP3A4 inducers
* Concurrent use of medications that interact with nitrate/nitrites
* Use of an investigational drug within 14 days preceding the first dose of study medication.
* Concurrent use of any complementary or alternative medicines
* Patients with \> Grade 2 neuropathy
* Inability to take aspirin
18 Years
FEMALE
No
Sponsors
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The Methodist Hospital Research Institute
OTHER
Responsible Party
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Polly A. Niravath, MD
Principal Investigator, Medical Oncologist
Principal Investigators
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Polly Niravath, M.D.
Role: PRINCIPAL_INVESTIGATOR
Houston Methodist Cancer Center
Locations
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Houston Methodist Hospital
Houston, Texas, United States
Countries
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Provided Documents
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Document Type: Study Protocol and Statistical Analysis Plan
Other Identifiers
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Pro00011685
Identifier Type: -
Identifier Source: org_study_id