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Tesetaxel Plus Reduced Dose of Capecitabine in Patients With HER2 Negative, HR Positive, LA/MBC (CONTESSA 2)

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ClinicalTrials.gov Identifier: NCT03858972
Recruitment Status : Recruiting
First Posted : March 1, 2019
Last Update Posted : March 28, 2019
Sponsor:
Information provided by (Responsible Party):
Odonate Therapeutics, Inc.

Tracking Information
First Submitted Date  ICMJE February 26, 2019
First Posted Date  ICMJE March 1, 2019
Last Update Posted Date March 28, 2019
Actual Study Start Date  ICMJE February 5, 2019
Estimated Primary Completion Date March 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 28, 2019)
ORR [ Time Frame: Approximately 2 - 2.5 years ]
Objective response rate
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03858972 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 28, 2019)
  • DoR [ Time Frame: Approximately 2 - 2.5 years ]
    Duration of response
  • PFS [ Time Frame: Approximately 2 - 2.5 years ]
    Progression-free survival
  • DCR [ Time Frame: Approximately 2 - 2.5 years ]
    Disease control rate
  • OS [ Time Frame: Approximately 3 - 3.5 years ]
    Overall survival
  • CNS ORR in patients with CNS metastases at baseline [ Time Frame: Approximately 2 - 2.5 years ]
    Central nervous system (CNS) objective response rate as assessed by the CNS IRC
  • CNS DoR in patients with CNS metastases at baseline [ Time Frame: Approximately 2 - 2.5 years ]
    CNS duration of response as assessed by the CNS IRC
  • 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 ]
    CNS progression-free survival as assessed by the CNS IRC
  • CNS OS in patients with CNS metastases at baseline or a history of CNS metastases [ Time Frame: Approximately 3 - 3.5 years ]
    CNS overall survival
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: February 28, 2019)
  • Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v5.0 [ Time Frame: Approximately 3 - 3.5 years ]
    Adverse Events will be collected at each visit and at unscheduled visits, as clinically indicated
  • Incidence of clinical laboratory abnormalities as assessed by CBC, serum chemistry and coagulation testing [ Time Frame: Approximately 3 - 3.5 years ]
    Laboratory data will be collected at each visit and at unscheduled visits, as appropriate
  • Peak plasma concentration (Cmax) of tesetaxel [ Time Frame: Approximately 2 - 2.5 years ]
    Maximum plasma concentration (Cmax) of tesetaxel
  • Area under the plasma concentration versus time curve (AUC) of tesetaxel [ Time Frame: Approximately 2 - 2.5 years ]
    Area under the curve (AUC) of tesetaxel
  • Peak plasma concentration (Cmax) of capecitabine and 5-FU [ Time Frame: Approximately 2 - 2.5 years ]
    Maximum plasma concentration (Cmax) of capecitabine and 5-FU
  • Area under the plasma concentration versus time curve (AUC) of capecitabine and 5-FU [ Time Frame: Approximately 2 - 2.5 years ]
    Area under the curve (AUC) of capecitabine and 5-FU
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Tesetaxel Plus Reduced Dose of Capecitabine in Patients With HER2 Negative, HR Positive, LA/MBC
Official Title  ICMJE 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
Brief Summary 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 complements 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Breast Cancer
Intervention  ICMJE
  • Drug: Tesetaxel
    Tesetaxel plus reduced dose of capecitabine
  • Drug: Capecitabine
    Reduced dose of capecitabine
Study Arms  ICMJE Experimental: Tesetaxel (oral) and capecitabine (oral)

Cohort 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.

Interventions:
  • Drug: Tesetaxel
  • Drug: Capecitabine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 28, 2019)
125
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 2022
Estimated Primary Completion Date March 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Jennifer Baca 910-769-1557 contessa2@odonate.com
Contact: Jill Krause 810-208-7254 contessa2@odonate.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03858972
Other Study ID Numbers  ICMJE ODO-TE-B201
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Odonate Therapeutics, Inc.
Study Sponsor  ICMJE Odonate Therapeutics, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Joseph O'Connell, MD Odonate Therapeutics, Inc.
PRS Account Odonate Therapeutics, Inc.
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP