The primary objective is to compare the efficacy of tesetaxel plus a reduced dose of
capecitabine versus the approved dose of capecitabine alone in patients with HER2 negative,
HR positive MBC previously treated with a taxane in the neoadjuvant or adjuvant setting.
Approximately 600 eligible patients will be randomly assigned in a 1:1 ratio to either Arm A
(tesetaxel plus a reduced dose of capecitabine) or Arm B (approved dose of capecitabine
alone).
This is a multinational, multicenter, randomized, open-label, parallel group Phase 3 study.
The primary objective is to compare the efficacy of tesetaxel plus a reduced dose of
capecitabine versus the approved dose of capecitabine alone based on PFS, as assessed by an
Independent Radiologic Review Committee (IRC), in patients with HER2 negative, HR positive
MBC previously treated with a taxane in the neoadjuvant or adjuvant setting.
Patients randomly assigned to Arm A (tesetaxel plus a reduced dose of capecitabine) will be
administered:
- Tesetaxel (27 mg/m2) orally once every 21 days on Day 1 of each 21-day cycle; and
- Capecitabine (825 mg/m2) orally twice daily (in the morning and evening after a meal,
for a total daily dose of 1,650 mg/m2) beginning with the evening dose on Day 1 through
the morning dose on Day 15 of each 21-day cycle
Patients randomly assigned to Arm B (approved dose of capecitabine alone) will be
administered:
• Capecitabine (1,250 mg/m2) orally twice daily (in the morning and evening after a meal, for
a total daily dose of 2,500 mg/m2), beginning with the evening dose on Day 1 through the
morning dose on Day 15 of each 21-day cycle Dose modifications for tesetaxel and/or
capecitabine are described in the Study protocol.
Patients will be treated until documentation of progressive disease (PD), evidence of
unacceptable toxicity, or other decision to discontinue treatment.
Inclusion Criteria:
1. Female or male patients at least 18 years of age
2. Histologically or cytologically confirmed breast cancer
3. HER2 negative disease based on local testing: American Society of Clinical
Oncology/College of American Pathologists (ASCO/CAP) guidelines should be utilized for
assessing HER2 status.
4. HR (ER and/or PgR) positive disease based on local testing: ASCO/CAP guidelines should
be utilized for assessing HR status.
5. Measurable disease per RECIST 1.1 or bone-only disease with lytic component. Patients
with bone-only metastatic cancer must have a lytic or mixed lytic-blastic lesion that
can be accurately assessed by computerized tomography (CT) or magnetic resonance
imaging (MRI). Patients with bone-only disease without a lytic component (ie,
blastic-only metastasis) are not eligible.
6. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
7. Prior therapy with a taxane-containing regimen in the neoadjuvant or adjuvant setting
8. Prior therapy with an anthracycline-containing regimen in the neoadjuvant, adjuvant,
or metastatic setting, where indicated
9. Prior endocrine therapy with or without a CDK 4/6 inhibitor unless endocrine therapy
is not indicated (ie, short relapse-free interval while on adjuvant endocrine therapy
[endocrine resistance]; rapidly progressing disease/visceral crisis; or endocrine
intolerance). Any targeted therapies approved for HER2 negative, HR positive MBC,
including everolimus, are permitted as prior therapy. There is no limit to the number
of prior endocrine therapies.
10. Documented disease recurrence or disease progression
11. Adequate bone marrow, hepatic, and renal function, as evidenced by:
- Absolute neutrophil count (ANC) ≥ 1,500/μL without colony-stimulating factor
support
- Platelet count ≥ 100,000/μL
- Hemoglobin ≥ 10 g/dL without need for hematopoietic growth factor or transfusion
support
- Total bilirubin < 1.5 × upper limit of normal (ULN); does not apply to patients
with Gilbert's syndrome
- Alanine aminotransferase (ALT) < 3 × ULN unless hepatic metastases are present,
then < 5 × ULN
- Aspartate aminotransferase (AST) < 3 × ULN unless hepatic metastases are present,
then < 5 × ULN
- Alkaline phosphatase < 2.5 × ULN unless hepatic metastases are present, then < 5
× ULN
- Calculated creatinine clearance ≥ 50 mL/min
- Serum albumin ≥ 3.0 g/dL
- Prothrombin time (PT) < 1.5 × ULN or international normalized ratio (INR) < 1.3
and partial thromboplastin time (PTT) < 1.5 × ULN; does not apply to patients on
a stable dose of anticoagulant
12. Complete recovery to baseline or Grade 1 per National Cancer Institute (NCI) Common
Terminology Criteria for Adverse Events (CTCAE) version 4.03 from adverse effects of
prior surgery, radiotherapy, endocrine therapy, and other therapy, as applicable
13. Ability to swallow an oral solid-dosage form of medication
14. A negative serum pregnancy test within 7 days prior to the first dose of Study
treatment in women of childbearing potential (ie, all women except those who are post
menopause for ≥ 1 year or who have a history of hysterectomy or surgical
sterilization)
15. Women of childbearing potential must use an effective, non-hormonal form of
contraception from Screening throughout the Treatment Phase and until the End of
Treatment visit.
• Acceptable methods include: copper intrauterine device or double barrier methods,
including male/female condoms with spermicide and use of contraceptive sponge,
cervical cap, or diaphragm
16. Male patients must use an effective, non-hormonal form of contraception from Screening
throughout the Treatment Phase and until 90 days after last dose of study treatment.
• Acceptable methods include male/female condoms with spermicide, or vasectomy with
medical confirmation of surgical success.
17. Written informed consent and authorization to use and disclose health information
18. Ability to comprehend and comply with the requirements of the Study
Exclusion Criteria:
1. Two or more prior chemotherapy regimens for advanced disease
2. Prior treatment with a taxane in the metastatic setting
3. Prior treatment with capecitabine
4. Known metastases to the central nervous system
5. Other cancer that required therapy within the preceding 5 years other than adequately
treated non-melanoma skin cancer or in situ cancer
6. Known human immunodeficiency virus infection, unless well controlled. Patients who are
on an adequate antiviral regimen with no evidence of active infection are considered
well controlled.
7. Active hepatitis B or active hepatitis C infection
8. Other severe acute or chronic medical or psychiatric condition or laboratory
abnormality that may increase the risk associated with Study participation or
investigational product administration or may interfere with the interpretation of
Study results and, in the judgment of the Investigator, would make the patient
inappropriate for entry into this Study.
9. Presence of neuropathy > Grade 1 per NCI CTCAE version 4.03
10. History of hypersensitivity to taxanes; hypersensitivity to the solvent does not
preclude patient participation in this Study
11. Anticancer treatment, including endocrine therapy, radiotherapy, chemotherapy, or
biologic therapy, ≤ 14 days prior to the date of Randomization
12. Major surgery ≤ 28 days prior to the date of Randomization; patient must have complete
recovery from surgery
13. 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 cytochrome P450 (CYP)3A or CYP2C9
pathways (patients should discontinue taking any regularly-taken medication that is a
potent inhibitor or inducer of the CYP3A or CYP2C9 pathways)
14. History of hypersensitivity to capecitabine, other fluoropyrimidine agents, or any of
their ingredients
15. Known dihydropyrimidine dehydrogenase (DPD) deficiency
16. Pregnant or breastfeeding
17. If, in the opinion of the Investigator, the patient is deemed unwilling or unable to
comply with the requirements of the Study
