A Multinational, Multicenter, Randomized, Phase 3 Study of Tesetaxel plus a Reduced Dose of Capecitabine versus Capecitabine Alone in Patients with HER2 Negative, Hormone Receptor Positive, Locally Advanced or Metastatic Breast Cancer Previously Treated with a Taxane

Protocol # :
Breast Cancer
Disease Sites
Principal Investigator
Tolaney, Sara, M
Site Investigator
Patel, Jaymin
Site Research Nurses
Caradonna, Lisa
Carrier, Amy
Livesey, Megan

Trial Description

CONTESSA is a multinational, multicenter, randomized, Phase 3 study of tesetaxel in
patients with HER2 negative, HR positive LA/MBC previously treated with a taxane in the
neoadjuvant or adjuvant setting. The primary objective of the study is to compare the
efficacy of tesetaxel plus a reduced dose of capecitabine versus the approved dose of
capecitabine alone based on progression-free survival (PFS) as assessed by the
Independent Radiologic Review Committee (IRC). 685 patients were enrolled.

Eligibility Requirements

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 (estrogen receptor [ER] and/or progesterone receptor [PgR]) positive disease
based on local testing: ASCO/CAP guidelines should be utilized for assessing HR

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.

- Known metastases to the CNS are permitted but not required. The following
criteria apply:

- Patients must be neurologically stable and either off corticosteroids or
currently treated with a maximum daily dose of 4 mg of dexamethasone (or
equivalent), with no increase in corticosteroid dose within 7 days prior
to randomization

- Patients with a history of CNS metastases but with no current evidence of
CNS lesions following local therapy are eligible

- Patients may have CNS metastases that are stable or progressing

- Patients with current evidence of leptomeningeal disease are not eligible

- Patients may have untreated brain metastases or previously treated brain
metastases, as long as no immediate local CNS-directed therapy is

- Any prior whole brain radiation therapy must have been completed > 14 days
prior to the date of randomization

- Prior stereotactic brain radiosurgery is permitted

- CNS surgical resection must have been completed > 28 days prior to the
date of randomization; patient must have complete recovery from surgery

6. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2

7. Prior therapy (at least one completed dose) 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 by local regulation or Investigator judgment.

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 LA/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 of: (a) locally advanced
disease that is not considered curable by surgery and/or radiation; or (b)
metastatic disease.

11. Adequate hematologic, hepatic and renal function, as evidenced by:

- Absolute neutrophil count (ANC) ≥ 1,500/μL without colony-stimulating factor

- 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 (by Cockcroft-Gault formula or
local standard)

- 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, unless the patient is
on a therapeutic anticoagulant

12. Complete recovery to baseline or Grade 1 per National Cancer Institute (NCI) CTCAE
version 5.0 from adverse effects of prior surgery, radiotherapy, endocrine therapy
and other therapy, as applicable, with the exception of Grade 2 alopecia from prior

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

15. Women of childbearing potential must use an effective, non-hormonal form of
contraception from Screening throughout the Treatment Phase and until 70 days after
the last dose of study treatment

• Acceptable methods include: copper intrauterine devices 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 130 days after last dose of study

• 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 at any dose

4. Current evidence of leptomeningeal disease

5. Other cancer that required therapy within the preceding 5 years other than
adequately treated: (a) non-melanoma skin cancer or in situ cancer; or (b) following
approval by the Medical Monitor, other cancer that has a very low risk of
interfering with the safety or efficacy endpoints of the study

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 5.0

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 (except stereotactic
brain radiosurgery), chemotherapy, biologic therapy, or therapy in an
investigational clinical study, ≤ 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 or 5 plasma half-lives (whichever is greater) since last use of a
medication or ingestion of an agent, beverage or food that is a known clinically
relevant strong inhibitor or known clinically relevant inducer of the cytochrome
P450 (CYP) 3A pathway (patients should discontinue taking any regularly taken
medication that is a strong inhibitor or inducer of the CYP3A pathway)

14. History of hypersensitivity or unexpected reactions to capecitabine, other
fluoropyrimidine agents or any of their ingredients

15. Known dihydropyrimidine dehydrogenase (DPD) deficiency. Testing for DPD deficiency
must be performed where required by local regulations, using a validated method that
is approved by local health authorities.

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

18. Treatment with brivudine, sorivudine or its chemically-related analogs ≤ 28 days
prior to the date of randomization