To Assess the Bioavailability and Safety of Paclitaxel Injection Concentrate for Suspension in Subjects With Locally Recurrent or Metastatic Breast Cancer

Study Overview
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Brief Summary
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A randomized, multi center, open label, two-period, single dose, crossover study to evaluate the bioavailability and safety of Paclitaxel Injection Concentrate for Suspension in Locally Recurrent or Metastatic Breast Cancer subjects.

Official Title
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A Randomized, Open Label, Two Period, Single Dose, Crossover, Bioavailability Study of Paclitaxel Injection Concentrate for Suspension (PICS) in Subjects With Locally Recurrent or Metastatic Breast Cancer.

Conditions
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Metastatic Breast Cancer, Locally Recurrent Cancer

Intervention / Treatment
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* Drug: PICS (Reconstitution Method 1 or 2)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The subject has given written, informed consent (or legally acceptable representative /impartial witness when applicable) and is available for the duration of study Histologically or cytologically confirmed diagnosis of breast cancer with adequate documentation of prior therapy with an anthracycline unless clinically contraindicated Locally recurrent or MBC for which taxane-based therapy is an appropriate treatment option Male or female aged greater than equal to 18 years ECOG performance status less than equal to 1 Estimated life expectancy of at least 12 weeks Adequate organ and immune system function as indicated by the following laboratory values, obtained less than equal to 2 weeks prior to dosing for Period 1 and Period 2: Any chemotherapy, targeted therapy, major surgery, or irradiation must have been completed at least 4 weeks before enrollment (6 weeks for mitomycin C or nitrosurea); immune therapy or hormonal therapy (except palliative bisphosphonate therapy for bone pain) must be completed 2 weeks before enrollment and subjects must have recovered from all toxicities incurred as a result of previous therapy except alopecia; use of targeted therapy or antibody therapy should have been completed for at least 5 half-lives of the respective therapy before enrollment. Use of narcotic analgesics such as dihydrocodeine and medicinal herbs such as St. John's Wort, which may act as inhibitors/inducers of CYP2C8 and CYP3A4, must have been discontinued at least 2 weeks and 4 weeks respectively before enrollment Subjects of child bearing potential must practice an acceptable method of birth control as judged by the investigator Medically acceptable methods of birth control include the use of either a contraceptive implant or a contraceptive injection (e.g., Depo-Provera™) or an intrauterine device, same sex partner or vasectomized partner or an oral contraceptive taken continually within the past three months and which the subject agrees to continue using during the study To adopt another birth control method, or a double-barrier method which consists of a combination of any two of the following: diaphragm, cervical cap, condom, or a spermicide at least 2 months prior to study entry and must continue to use contraception for the duration of the study Female subjects who are postmenopausal for at least 1 year as per investigator's discretion, or who are surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy has been performed on the subject) Male subjects enrolled in the trial cannot father a child and are advised to prevent passage of semen to their sexual partner during intercourse using acceptable methods as judged by the investigator for the duration of the study Females subjects of child-bearing potential must have a negative urine pregnancy test Female subjects must be non-lactating and non-breastfeeding Subject must be willing and able to comply with scheduled visits, treatment plan and laboratory testing. Exclusion Criteria: Known hypersensitivity to the study drug or their excipients (cholesteryl sulfate, caprylic acid, polyvinylpyrrolidone, ethanol, polyethylene glycol) Inability to undergo venipuncture and/or tolerate venous access Presence of clinically symptomatic active CNS metastases, including leptomeningial involvement, requiring steroid or radiation therapy Pre-existing clinically significant peripheral neuropathy (Grade 2 or higher according to CTCAE, Version 5.0) Any other severe concurrent disease which in the judgment of the investigator would make the subject inappropriate for entry into this study or confound the study Presence of pleural/ascitic fluid which cannot be definitively treated prior to dosing and during the PK blood draws in each period (Period 1 and Period 2) and if there is re-accumulation of fluid (greater than 5%) greater than 2 weeks after definitive management Positive laboratory exclusion test (HIV, HBsAg, or HCV) Treatment with investigational agents or participation in a clinical trial within 30 days of study entry Failure of prior taxane therapy for metastatic disease or for adjuvant therapy within previous 6 months of screening visit Subjects taking concurrent medications that may act as inhibitors/inducers of CYP2C8 and CYP3A4 within 2 weeks of screening and during Periods 1 and 2 Evidence or history of bleeding diathesis or coagulopathy within 6 months prior to screening visit Uncontrolled cardiac disease, including: congestive heart failure (CHF) > Class II per New York Heart Association (NYHA), history of hypertensive crisis Active clinical infection which in the treating investigator's opinion renders the subject ineligible or can confound the study Serious non-healing wound, ulcer or bone fracture Unresolved toxicity higher than CTCAE Version 5.0 Grade 1 (excluding alopecia, anemia) attributed to any prior therapy/procedure History of gastrointestinal perforation within 6 months prior to screening visit.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Reconstitution Method 1<br> | Drug: PICS (Reconstitution Method 1 or 2)<br>* dose: 260mg/m2 Frequency: 2 period cross over study Route of administration : intravenous infusion duration of therapy: 2 cycles of PICS<br>|
| Active Comparator: Reconstitution Method 2<br> | Drug: PICS (Reconstitution Method 1 or 2)<br>* dose: 260mg/m2 Frequency: 2 period cross over study Route of administration : intravenous infusion duration of therapy: 2 cycles of PICS<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum observed plasma concentration Plasma |  | 8 weeks | 
| area under the plasma concentration versus time curve, from time 0 to the last measurable concentration |  | 8 weeks | 
| area under the plasma concentration versus time curve from time 0 to infinity |  | 8 weeks | 
| Incidence of Treatment-Emergent Adverse Events | shall be coded per CTCAE, Version 5.0 | 8 weeks |