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

Phase 1

• Conditions: Patients with Breast Cancer; Therapeutic area: Diseases [C] - Cancer [C04]; MedDRA version: 20.1Level: PTClassification code 10055113Term: Breast cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

• Registration Number: EUCTR2017-002961-23-IT
• Lead Sponsor: ODONATE THERAPEUTICS

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-05-25
• Last Update Posted: 7 September 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 600

Inclusion Criteria

1. F or M pats. 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 Progesteron Receptor (PgR)) positive disease based on local testing: ASCO/CAP guidelines should be utilized for assessing HR status.
5. Measurable disease per Response Evaluation Criteria in Solid Tum. (RECIST) 1.1 or bone-only disease with lytic component. Pats. 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). Pats. 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: (see Protocol)..
6. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2 (Oken Am J Clin Oncol. 1982 Dec;5(6):649-55)
7. Prior ther. (at least one completed dose) with a taxane-containing regimen in the neoadjuvant or adjuvant setting
8. Prior ther. with an anthracycline-containing regimen in the neoadjuvant, adjuvant, or metastatic setting, where indicated by local
regulation or Investigator judgement
9. Prior endocr. ther. with or without a Cyclin dependant kinase (CDK) 4/6 inhibitor unless endocr.e ther. is not indicated (ie, short relapse-free interval while on adjuvant endocr.e ther. [endocr.eresistance]; rapidly progressing disease/visceral crisis; or endocr.e intolerance). Any targeted ther. approved for HER2 negative, HR positive MBC, including everolimus, are permitted as prior ther.. There is no limit to the number of prior endocr. ther..
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 support
PLA = 100,000/µL
Hb = 10 g/dL without need for hematopoietic growth factor or transfusion support
Total bil < 1.5 × upper limit of normal (ULN); does not apply to pats. with Gilbert's syndrome
ALT < 3 × ULN unless hepatic metast. are present then < 5 × ULN
(AST < 3 × ULN unless hepatic metast. are present then < 5 × ULN
Alkaline phosphatase < 2.5 × ULN unless hepatic metast. are present then < 5 × ULN
Calculated creatinine clearance = 50 mL/min (by Cockcroft-Gault formula or local standard)
Serum albumin = 3.0 g/dL
PT < 1.5 × ULN or INR < 1.3 and PTT < 1.5 × ULN; unless the pat. is on a therapeutic anticoagulant
12. Complete recovery to baseline or Grade 1 per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 from adverse effects of prior surgery, radiother., endocr.e ther., and other ther., as applicable with the exception of Grade 2 alopecia from prior chemother.
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, nonhormonal form

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. Known metastases to the central nervous system
5. Other cancer that required therapy within the preceding 5 years other than adequately treated a) non-melanoma skin cancer or in situ cancer
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 National Cancer Institute Common Terminology Criteria for Adverse Events (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, 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 potent inhibitor or inducer of the cytochrome P450 (CYP)3A or CYP2C9 pathways (patients should discontinue taking any regularlytaken medication that is a potent inhibitor or inducer of the CYP3A or CYP2C9 pathways [refer to Appendix C])
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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified