Metastatic Breast Cancer
Conditions
Brief summary
The current study is being conducted to find an optimal Oral Paclitaxel + Encequidar dose and regimen based on prior experience with oral paclitaxel (stage 1) and to compare that dose to an accepted dose and regimen of intravenous (IV) paclitaxel in subjects with metastatic breast cancer (stage 2).
Interventions
DRUGPaclitaxel Capsule
Paclitaxel Capsule
DRUGIV Paclitaxel
IV Paclitaxel
DRUGEncequidar tablet
Encequidar tablet
Sponsors
Health Hope Pharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
HHP-ORAX-300 is a Phase 3, open-label, randomized, two-stage dose optimization and noninferiority study. The study includes 2 stages: Stage 1 is a dose-optimization design that will select an Oral Paclitaxel + Encequidar regimen to test against IV paclitaxel 80 mg/m2 in a confirmatory Stage 2.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Signed written informed consent 2. ≥18 years of age 3. Histologically or cytologically confirmed HER2 negative breast cancer for whom IV paclitaxel monotherapy has been recommended. 4. HER2 negative per American Society of Clinical Oncology (ASCO) College of American Pathologists (CAP) guideline. Subjects can be estrogen receptor/progesterone receptor (ER/PR) positive or negative per ASCO CAP guideline, but ER/PR and HER2 receptor status must be known. 5. Metastatic breast cancer with target lesions measurable by CT scan per RECIST v1.1 criteria confirmed by BICR 6. Adequate hematologic status as demonstrated by not requiring granulocyte colony stimulating factor (G CSF) or transfusion support within 30 days prior to randomization to achieve the following at screening: * Absolute neutrophil count (ANC) ≥1500/mm3 * Platelet count ≥100,000/mm3 * Hemoglobin ≥9 g/dL 7. Adequate liver function as demonstrated by: * Total bilirubin ≤upper limit of normal (ULN) unless the subject has Gilbert's disease, for which bilirubin must be ≤2.0 × ULN * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤1.5 × ULN 8. Adequate renal function as demonstrated by estimated glomerular filtration rate (eGFR) ≥60 mL/min 9. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 10. Life expectancy at least 6 months, in the judgment of the Investigator 11. Female subjects must be postmenopausal (≥12 months without menses) or surgically sterile (ie, by hysterectomy, bilateral oophorectomy, or bilateral tubal ligation) or must be using effective contraception (ie, non-hormonal intrauterine device, double barrier method of condom and spermicide) and agree to continue use of contraception for 30 days after their last dose of assigned study treatment. 12. Women of childbearing potential must have a negative screening serum pregnancy test and urine test within 4 days prior to start of dosing in the study and not be breast feeding. 13. Sexually active male subjects must use a barrier method of contraception during the study and agree to continue the use of male contraception for at least 30 days after the last dose of investigational product (IP).
Exclusion criteria
1. Not recovered to ≤grade 1 toxicity from previous anticancer treatments or previous investigational product (IP) except alopecia 2. QTcF interval ≥470 msec at baseline 3. Relapsed less than 6 months following treatment with a taxane (paclitaxel or docetaxel) as part of anthracycline-based adjuvant chemotherapy or for metastatic disease 4. Known active central nervous system metastasis, including leptomeningeal involvement 5. Currently receiving other medications intended for the treatment of their malignancy 6. Received other IPs within 14 days or 5 half-lives of the first study dosing day, whichever is longer 7. Received biologics or monoclonal antibodies intended for the treatment of their malignancy within 30 days of the first study dosing day 8. Received radiation therapy within 2 weeks prior to signing informed consent or radiation therapy is planned within 6 months from the time of signing informed consent 9. Taking a medication known to be a moderate or strong cytochrome P450 (CYP) 3A4 inhibitor or inducer or neurokinin-1 receptor antagonist (NK-1) inhibitor within 14 days prior to start of dosing in the study 10. Taking a medication known to be a moderate or strong CYP2C8 inhibitor or inducer within 14 days prior to start of dosing in the study 11. Taking an oral medication with a narrow therapeutic index known to be a P-glycoprotein (P-gp) substrate within 24 hours prior to start of dosing in the study 12. Taking a medication known to be a P-gp inhibitor or inducer within 14 days prior to start of dosing in the study 13. Taking a medication known to be an organic anion transporting polypeptide 1B1/3 (OATP1B1/3) inhibitor 14. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, myocardial infarction within the last 6 months, unstable angina pectoris, cardiac arrhythmia, chronic pulmonary disease requiring oxygen, known bleeding disorders, or any concomitant illness or social situation that would limit compliance with study requirements 15. Major surgery to the upper GI tract, inability to take oral medication, or have a history of GI disease or other medical condition that, in the opinion of the Investigator may interfere with oral drug absorption 16. History of significant hypersensitivity-type reaction to paclitaxel or Cremophor EL that would contraindicate the use of IV paclitaxel 17. Known allergic reaction or intolerance to contrast media 18. Documented history of true systemic allergic reaction to 3 or more medications 19. Active hepatitis B (as evidenced by being HBsAg positive) or active hepatitis C (HCV-RNA positive) or cirrhosis of the liver 20. Known HIV infection 21. The Investigator believes that participation in this study would not be acceptable
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Stage 1: Confirmed Tumor Response | 6 months | Confirmed tumor response based on BICR timepoint evaluations of CT scans using RECIST v1.1 criteria |
| Stage 2: Confirmed Tumor Response | 1 Year | Confirmed tumor response based on BICR timepoint evaluations of CT scans using RECIST v1.1 criteria |
Outcome results
None listed