Phase 2
N=37
L-NMMA Plus Taxane Chemotherapy in Refractory Locally Advanced or Metastatic Triple Negative Breast Cancer Patients
Metastatic Triple Negative Breast Cancer
Bottom Line
View on ClinicalTrials.gov: NCT02834403 ↗Enrolled (actual)
37
Serious AEs
22.9%
Results posted
Dec 2023
Primary outcome: Primary: Asses the Maximum Tolerated Dose (MTD) of L-NMMA When Combined With Docetaxel/Amlodipine in the Treatment of Refractory Locally Advanced or Metastatic TNBC Patients, Based on the Number of Dose Limiting Toxicities (DLTs) Per Dose Level. — 20 mg/kg
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- L-NMMA (Drug); Docetaxel (Drug); Amlodipine (Drug); Pegfilgrastim (Drug); Enteric-coated aspirin (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- Female
- Sponsor
- The Methodist Hospital Research Institute
- Primary completion
- Jan 2021
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Asses the Maximum Tolerated Dose (MTD) of L-NMMA When Combined With Docetaxel/Amlodipine in the Treatment of Refractory Locally Advanced or Metastatic TNBC Patients, Based on the Number of Dose Limiting Toxicities (DLTs) Per Dose Level. |
20 | — |
| PRIMARY Clinical Benefit Rate |
0; 2; 3; 6; 2; 4 | — |
| PRIMARY Asses the Maximum Tolerated Dose (MTD) of Docetaxel When Combined With L-NMMA/Amlodipine in the Treatment of Refractory Locally Advanced or Metastatic TNBC Patients, Based on the Number of Dose Limiting Toxicities (DLTs) Per Dose Level. |
100 | — |
| SECONDARY Dose Limiting Toxicities (DLTs) and Other Adverse Events |
0; 0; 0; 0; 2; 1 | — |
| SECONDARY Recommended Phase 2 Dose (RP2D) of the L-NMMA and Docetaxel Combination |
100 | — |
| SECONDARY Antitumor Activity |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Time to Maximum Plasma Concentration of L-NMMA and Docetaxel |
2; 2; 4; 4 | — |
Summary
This is a Phase Ib/II study assessing the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), recommended Phase 2 dose (RP2D), and efficacy of L-NMMA when combined with docetaxel in refractory locally advanced or metastatic triple negative breast cancer patients. The Phase Ib portion of the study is designed to investigate the combination at two dose levels of docetaxel (75 and 100 mg/m2) and 7 dose levels of L-NMMA (5, 7.5, 10, 12.5, 15, 17.5, and 20 mg/kg). The starting dose of L-NMMA will be 7.5 mg/kg. In the Phase II portion of the study, the starting dose will be the RP2D determined in the Phase Ib portion of the study.
Eligibility Criteria
Inclusion Criteria
Patient must meet all of the following 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 ( 150 mmHg at baseline)
- 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 Grade 2 neuropathy
- Inability to take aspirin
Data sourced from ClinicalTrials.gov (NCT02834403). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.