Summary

for people ages 18 years and up (full criteria)
at San Francisco, California and other locations
study started
estimated completion:
Hope Rugo

Description

Summary

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 LA/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).

Official Title

Randomized, Phase 3 Study of Tesetaxel Plus a Reduced Dose of Capecitabine Versus Capecitabine Alone in Patients With HER2 Negative, HR Positive, Locally Advanced or Metastatic Breast Cancer Previously Treated With a Taxane

Details

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, LA/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.

Keywords

Breast Cancer Tesetaxel Capecitabine HER2 negative Hormone Receptor positive Locally advanced or metastatic breast cancer Combination of tesetaxel and capecitabine Taxanes Metastatic breast cancer Central nervous system (CNS) metastases Breast Neoplasms Tesetaxel and Capecitabine

Eligibility

You can join if…

Open to people ages 18 years and up

  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.
  6. 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.
  7. Known metastases to the central nervous system (CNS) are permitted but not required. The following criteria apply:
  8. 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
  9. Patients with a history of CNS metastases but with no current evidence of CNS lesions following local therapy are eligible
  10. Patients may have CNS metastases that are stable or progressing radiologically
  11. Patients with current evidence of leptomeningeal disease are not eligible
  12. Patients may have untreated brain metastases or previously treated brain metastases, as long as no immediate local CNS-directed therapy is indicated
  13. Any prior whole brain radiation therapy must have been completed > 14 days prior to the date of Randomization
  14. Prior stereotactic brain radiosurgery is permitted
  15. CNS surgical resection must have been completed > 28 days prior to the date of Randomization; patient must have complete recovery from surgery
  16. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
  17. Prior therapy (at least one completed dose) with a taxane-containing regimen in the neoadjuvant or adjuvant setting
  18. Prior therapy with an anthracycline-containing regimen in the neoadjuvant, adjuvant,or metastatic setting, where indicated by local regulation or Investigator judgment.
  19. 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.
  20. . 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.
  21. . Adequate hematologic, hepatic, and renal function, as evidenced by:
  22. Absolute neutrophil count (ANC) ≥ 1,500/μL without colony-stimulating factor support
  23. Platelet count ≥ 100,000/μL
  24. Hemoglobin ≥ 10 g/dL without need for hematopoietic growth factor or transfusion support
  25. Total bilirubin < 1.5 × upper limit of normal (ULN); does not apply to patients with Gilbert's syndrome
  26. Alanine aminotransferase (ALT) < 3 × ULN unless hepatic metastases are present,then < 5 × ULN
  27. Aspartate aminotransferase (AST) < 3 × ULN unless hepatic metastases are present,then < 5 × ULN
  28. Alkaline phosphatase < 2.5 × ULN unless hepatic metastases are present, then < 5× ULN
  29. Calculated creatinine clearance ≥ 50 mL/min
  30. Serum albumin ≥ 3.0 g/dL
  31. 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
  32. . 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, radiotherapy, endocrine therapy, and other therapy, as applicable, with the exception of Grade 2 alopecia from prior chemotherapy
  33. . Ability to swallow an oral solid-dosage form of medication
  34. . 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)
  35. . 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 device or double barrier methods,including male/female condoms with spermicide and use of contraceptive sponge,cervical cap, or diaphragm

  1. . 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 treatment

• Acceptable methods include male/female condoms with spermicide, or vasectomy with medical confirmation of surgical success.

  1. . Written informed consent and authorization to use and disclose health information
  2. . Ability to comprehend and comply with the requirements of the Study

You CAN'T join if...

  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 surgery), 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

Locations

  • University of California San Francisco - Helen Diller Family Comprehensive Cancer Center accepting new patients
    San Francisco California 94115 United States
  • California Cancer Associates for Research and Excellence accepting new patients
    Fresno California 93720 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Odonate Therapeutics, LLC
ID
NCT03326674
Phase
Phase 3
Lead Scientist
Hope Rugo
Study Type
Interventional
Last Updated