Clinical Trials /

Tesetaxel Plus Reduced Dose of Capecitabine in Patients With HER2 Negative, HR Positive, LA/MBC

NCT03858972

Description:

CONTESSA 2 is a multinational, multicenter, Phase 2 study of tesetaxel in patients with taxane-naïve, HER2 negative, HR positive, locally advanced or metastatic breast cancer (LA/MBC). The primary objective of the study is to establish the efficacy of tesetaxel plus a reduced dose of capecitabine, based on objective response rate (ORR) as assessed by an Independent Radiologic Review Committee (IRC). Approximately 125 patients will be enrolled.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Tesetaxel Plus Reduced Dose of Capecitabine in Patients With HER2 Negative, HR Positive, LA/MBC
  • Official Title: Multinational, Multicenter, Phase 2 Study of Tesetaxel Plus a Reduced Dose of Capecitabine in Patients With HER2 Negative, Hormone Receptor Positive, Locally Advanced or Metastatic Breast Cancer Who Have Not Previously Received a Taxane

Clinical Trial IDs

  • ORG STUDY ID: ODO-TE-B201
  • NCT ID: NCT03858972

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
TesetaxelTesetaxel (oral) and capecitabine (oral)
CapecitabineTesetaxel (oral) and capecitabine (oral)

Purpose

CONTESSA 2 is a multinational, multicenter, Phase 2 study of tesetaxel in patients with taxane-naïve, HER2 negative, HR positive, locally advanced or metastatic breast cancer (LA/MBC). The primary objective of the study is to establish the efficacy of tesetaxel plus a reduced dose of capecitabine, based on objective response rate (ORR) as assessed by an Independent Radiologic Review Committee (IRC). Approximately 125 patients will be enrolled.

Detailed Description

      CONTESSA 2 is a multinational, multicenter, Phase 2 study of tesetaxel, an investigational,
      orally administered taxane, in patients with HER2 negative, HR Positive, LA/MBC not
      previously treated with a taxane in the neoadjuvant, adjuvant or metastatic setting. This
      Study will supplement CONTESSA, a multinational, multicenter, randomized, Phase 3 study in
      patients with HER2 negative, HR positive LA/MBC previously treated with a taxane in the
      neoadjuvant or adjuvant setting. In CONTESSA 2, approximately 125 patients will be enrolled
      to receive tesetaxel at 27 mg/m2 orally once every 21 days on the first day of each 21-day
      cycle plus capecitabine at 825 mg/m2 orally twice daily (for a total daily dose of 1,650
      mg/m2) for 14 days of each 21-day cycle. Patients in the dense pharmacokinetics (PK) cohort
      will also receive a single dose of capecitabine monotherapy prior to starting the combination
      regimen. Capecitabine is an oral chemotherapy agent that is considered a standard-of-care
      treatment in LA/MBC. The primary endpoint is ORR as assessed by an IRC. The secondary
      efficacy endpoints are duration of response as assessed by the IRC, progression-free survival
      as assessed by the IRC, disease control rate as assessed by the IRC and overall survival.
      CONTESSA 2 will also investigate the PK of tesetaxel.
    

Trial Arms

NameTypeDescriptionInterventions
Tesetaxel (oral) and capecitabine (oral)ExperimentalCohort 1: Tesetaxel (27 mg/m2) once every 21 days on Day 1 of each 21-day cycle; and capecitabine (825 mg/m2) twice daily (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. Cohort 2: On Cycle 1, Day -1, either a single morning dose of capecitabine at 825 mg/m2 (Cohort 2A) or 1,250 mg/m2 (Cohort 2B). On Cycle 1, Day 1, a single dose of tesetaxel (27 mg/m2), followed 2 hours later by capecitabine (825 mg/m2), followed by an evening dose of capecitabine (825 mg/m2). Capecitabine (825 mg/m2) twice daily (total daily dose of 1,650 mg/m2) beginning with the morning dose on Day 2 through evening dose on Day 14 of Cycle 1. Starting with Cycle 2, tesetaxel (27 mg/m2) once every 21 days on Day 1 of each 21-day cycle; and capecitabine (825 mg/m2) twice daily (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
  • 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, including bone-only disease with measurable lytic
             component.

             Patients with bone-only metastatic cancer must have a measurable 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
             measurable 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
                  Enrollment (defined as the time of Sponsor approval of treatment dose)

               -  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 radiologically

               -  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 indicated

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

               -  Prior stereotactic brain radiosurgery is permitted

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

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

          7. 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.

          8. Documented (including de novo): (a) locally advanced breast cancer that is not
             considered curable by surgery and/or radiation; or (b) metastatic breast cancer

          9. Adequate hematologic, 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 (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

         10. 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

         11. Ability to swallow an oral solid-dosage form of medication

         12. 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)

         13. 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

         14. Male patients must use an effective, non-hormonal form of contraception from Screening
             throughout the Treatment Phase and until 130 days after the last dose of Study
             treatment

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

         15. Written informed consent and authorization to use and disclose health information

         16. 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 at any dose

          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. 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 Enrollment

         11. Major surgery ≤ 28 days prior to the date of Enrollment; patient must have complete
             recovery from surgery

         12. 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)

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

         14. 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.

         15. Pregnant or breastfeeding

         16. If, in the opinion of the Investigator, the patient is deemed unwilling or unable to
             comply with the requirements of the Study

         17. Treatment with brivudine, sorivudine, or its chemically-related analogs ≤ 28 days
             prior to the date of Enrollment
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:ORR
Time Frame:Approximately 2 - 2.5 years
Safety Issue:
Description:Objective response rate

Secondary Outcome Measures

Measure:DoR
Time Frame:Approximately 2 - 2.5 years
Safety Issue:
Description:Duration of response
Measure:PFS
Time Frame:Approximately 2 - 2.5 years
Safety Issue:
Description:Progression-free survival
Measure:DCR
Time Frame:Approximately 2 - 2.5 years
Safety Issue:
Description:Disease control rate
Measure:OS
Time Frame:Approximately 3 - 3.5 years
Safety Issue:
Description:Overall survival
Measure:CNS ORR in patients with CNS metastases at baseline
Time Frame:Approximately 2 - 2.5 years
Safety Issue:
Description:Central nervous system (CNS) objective response rate as assessed by the CNS IRC
Measure:CNS DoR in patients with CNS metastases at baseline
Time Frame:Approximately 2 - 2.5 years
Safety Issue:
Description:CNS duration of response as assessed by the CNS IRC
Measure:CNS PFS in patients with CNS metastases at baseline or a history of CNS metastases and in the intent-to-treat (ITT) population
Time Frame:Approximately 2 - 2.5 years
Safety Issue:
Description:CNS progression-free survival as assessed by the CNS IRC
Measure:CNS OS in patients with CNS metastases at baseline or a history of CNS metastases
Time Frame:Approximately 3 - 3.5 years
Safety Issue:
Description:CNS overall survival

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Odonate Therapeutics, Inc.

Trial Keywords

  • Tesetaxel
  • Capecitabine
  • HER2 negative
  • Combination of tesetaxel and capecitabine
  • Taxane-naive
  • Locally advanced or metastatic breast cancer
  • Hormone receptor positive
  • Metastatic breast cancer (MBC)
  • Breast cancer
  • Central nervous system (CNS) metastases
  • de novo metastatic breast cancer
  • Oral chemotherapy
  • Taxane

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