Clinical Trials /

Tesetaxel Plus Reduced Dose of Capecitabine vs. Capecitabine in HER2 Negative, HR Positive, LA/MBC

NCT03326674

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 an Independent Radiologic Review Committee (IRC). Approximately 600 patients will be enrolled.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Tesetaxel Plus Reduced Dose of Capecitabine vs. Capecitabine in HER2 Negative, HR Positive, MBC (CONTESSA)
  • 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

Clinical Trial IDs

  • ORG STUDY ID: ODO-TE-B301
  • NCT ID: NCT03326674

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
Tesetaxel and CapecitabineArm A: Tesetaxel and Capecitabine
CapecitabineArm B: Capecitabine

Purpose

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).

Detailed Description

      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.
    

Trial Arms

NameTypeDescriptionInterventions
Arm A: Tesetaxel and CapecitabineExperimentalTesetaxel (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
  • Tesetaxel and Capecitabine
Arm B: CapecitabineActive ComparatorCapecitabine (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
  • Capecitabine

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:PFS
Time Frame:Approximately 2.5 - 3 years
Safety Issue:
Description:Progression Free Survival

Secondary Outcome Measures

Measure:OS
Time Frame:Approximately 5 - 5.5 years
Safety Issue:
Description:Overall Survival
Measure:ORR
Time Frame:Approximately 2.5 - 3 years
Safety Issue:
Description:Objective Response Rate
Measure:DCR
Time Frame:Approximately 2.5 - 3 years
Safety Issue:
Description:Disease Control Rate

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Odonate Therapeutics, LLC

Trial Keywords

  • Tesetaxel
  • Capecitabine
  • HER2 negative
  • Hormone Receptor positive
  • Locally advanced or metastatic breast cancer
  • Combination of tesetaxel and capecitabine
  • Taxanes
  • Metastatic breast cancer
  • Breast cancer

Last Updated

December 1, 2017