Tesetaxel Every 3 Weeks vs Weekly vs Capecitabine as 1st-line Therapy for Locally Advanced or Metastatic Breast Cancer

Study Overview
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Brief Summary
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This study is being conducted to compare the efficacy and safety of tesetaxel administered once every 3 weeks in a 21-day cycle, tesetaxel administered once weekly for 3 consecutive weeks in a 28-day cycle, and capecitabine administered twice daily for 14 consecutive days in a 21-day cycle.

Official Title
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A Randomized, Phase II Study of Tesetaxel Once Every 3 Weeks Versus Tesetaxel Once Weekly for 3 Weeks Versus Capecitabine Twice Daily for 14 Days as First-line Therapy for Subjects With Locally Advanced or Metastatic Breast Cancer

Conditions
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Locally Advanced Non-resectable Breast Cancer, Metastatic Breast Cancer

Intervention / Treatment
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* Drug: Tesetaxel
* Drug: Tesetaxel
* Drug: Capecitabine


Participation Criteria
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Eligibility Criteria
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Key inclusion criteria: Female At least 18 years of age Locally advanced non-resectable or metastatic breast cancer HER2 negative disease Measurable disease per revised RECIST, Version 1.1 Eastern Cooperative Oncology Group performance status 0 or 1 Chemotherapy naïve, OR 1 prior chemotherapy regimen in the neoadjuvant or adjuvant setting provided the patient has had a disease-free interval of ≥ 12 months after ending this chemotherapy. If the neoadjuvant or adjuvant chemotherapy included a taxane, ≥ 2 years must have passed since this treatment ended. Documented disease recurrence or progression Adequate bone marrow, hepatic, and renal function Ability to swallow an oral solid-dosage form of medication Written informed consent Key exclusion criteria: Known metastasis to the central nervous system Other cancer within the preceding 5 years other than curatively treated basal or squamous cell carcinoma of the skin or carcinoma of the cervix in situ Significant medical disease other than breast cancer Presence of neuropathy > Grade 1 (NCI CTC) History of hypersensitivity to a taxane or capecitabine, other fluoropyrimidine agents, or any of their ingredients History of severe or unexpected reaction to fluoropyrimidine therapy Need to continue any regularly-taken medication that is a potent inhibitor or inducer of the CYP3A pathway Less than 2 weeks since use of a medication or ingestion of an agent, beverage, or food that is a potent inhibitor or inducer of the CYP3A pathway Known dihydropyrimidine dehydrogenase deficiency Pregnancy or lactation

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tesetaxel every 3 weeks<br>Tesetaxel 27 mg/m2 orally on Day 1 in a 21-day cycle | Drug: Tesetaxel<br>* Tesetaxel 27 mg/m2 orally once on Day 1 of each 21-day cycle<br>|
| Experimental: Tesetaxel weekly<br>Tesetaxel 15 mg/m2 orally once every 7 days for 3 consecutive weeks on Day 1, Day 8, and Day 15 in a 28-day cycle | Drug: Tesetaxel<br>* Tesetaxel 15 mg/m2 orally once every 7 days for 3 consecutive weeks on Day 1, Day 8, and Day 15 of each 28-day cycle<br>|
| Active Comparator: Capecitabine<br>Capecitabine 1250 mg/m2 orally twice daily (equivalent to a total daily dose of 2500 mg/m2) on Day 1 through Day 14 in a 21-day cycle | Drug: Capecitabine<br>* Capecitabine 1250 mg/m2 orally twice daily (in the morning and evening after a meal; equivalent to a total daily dose of 2500 mg/m2) on Day 1 through Day 14 of each 21-day cycle<br>* Other names: Xeloda;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate | the percentage of patients with a confirmed complete or partial response, as defined in the revised Response Evaluation Criteria in Solid Tumors (revised RECIST [Version 1.1]) | 4 months after the date of randomization of the last patient, which is estimated will occur 16 months after the first patient is randomized | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical benefit rate | the percentage of patients with a complete or partial response of any duration or stable disease lasting ≥ 6 months | 12 months after the date of randomization of the last patient, which is estimated will occur 24 months after the first patient is randomized | 
| Progression-free survival | the period from the date of randomization to the date when disease progression is first documented or when the patient dies within 6 weeks of the last lesion assessment | 12 months after the date of randomization of the last patient, which is estimated will occur 24 months after the first patient is randomized | 
| Progression-free survival rate | the percentage of patients who are progression free | 6 and 12 months after patients' date of randomization | 
| Adverse events | the percentage of patients with adverse events classified by term and body system | up to 30 days after patients' last dose of study medication |