Trial Review

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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03858972




Registration number
NCT03858972
Ethics application status
Date submitted
26/02/2019
Date registered
1/03/2019
Date last updated
30/07/2021

Titles & IDs
Public title
Tesetaxel Plus Reduced Dose of Capecitabine in Patients With HER2 Negative, HR Positive, LA/MBC
Scientific 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
Secondary ID [1] 0 0
ODO-TE-B201
Universal Trial Number (UTN)
Trial acronym
CONTESSA 2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Tesetaxel
Treatment: Drugs - Capecitabine

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.


Treatment: Drugs: Tesetaxel
Tesetaxel plus reduced dose of capecitabine

Treatment: Drugs: Capecitabine
Reduced dose of capecitabine
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
ORR as assessed by the IRC
Timepoint [1] 0 0
Approximately 2.0-2.5 years
Secondary outcome [1] 0 0
DoR as assessed by the IRC
Timepoint [1] 0 0
Approximately 2.0-2.5 years
Secondary outcome [2] 0 0
PFS as assessed by the IRC
Timepoint [2] 0 0
Approximately 2.0-2.5 years
Secondary outcome [3] 0 0
DCR as assessed by the IRC
Timepoint [3] 0 0
Approximately 2.0-2.5 years
Secondary outcome [4] 0 0
OS
Timepoint [4] 0 0
Approximately 3.0-3.5 years
Secondary outcome [5] 0 0
Central nervous system (CNS) ORR as assessed by the CNS IRC in patients with CNS metastases at baseline
Timepoint [5] 0 0
Approximately 2.0-2.5 years
Secondary outcome [6] 0 0
CNS DoR as assessed by the CNS IRC in patients with CNS metastases at baseline
Timepoint [6] 0 0
Approximately 2.0-2.5 years
Secondary outcome [7] 0 0
CNS PFS as assessed by the CNS IRC in patients with CNS metastases at baseline or a history of CNS metastases and in the intent-to-treat (ITT) population
Timepoint [7] 0 0
Approximately 2.0-2.5 years
Secondary outcome [8] 0 0
CNS OS in patients with CNS metastases at baseline or a history of CNS metastases
Timepoint [8] 0 0
Approximately 3.0-3.5 years

Eligibility
Key inclusion 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 computed 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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, 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

Study design
Purpose of the study
Treatment
Allocation to intervention
NA
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
5/02/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
11/06/2021
Sample size
Target
Accrual to date
Final
152
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Border Medical Oncology - Albury
Recruitment postcode(s) [1] 0 0
2640 - Albury
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Massachusetts
Country [5] 0 0
United States of America
State/province [5] 0 0
New York
Country [6] 0 0
United States of America
State/province [6] 0 0
Tennessee
Country [7] 0 0
United States of America
State/province [7] 0 0
Texas
Country [8] 0 0
United States of America
State/province [8] 0 0
Virginia
Country [9] 0 0
Canada
State/province [9] 0 0
Montréal
Country [10] 0 0
Canada
State/province [10] 0 0
Québec
Country [11] 0 0
Canada
State/province [11] 0 0
Sherbrooke
Country [12] 0 0
Korea, Republic of
State/province [12] 0 0
Daegu
Country [13] 0 0
Korea, Republic of
State/province [13] 0 0
Goyang
Country [14] 0 0
Korea, Republic of
State/province [14] 0 0
Seoul
Country [15] 0 0
Korea, Republic of
State/province [15] 0 0
Suwon
Country [16] 0 0
Spain
State/province [16] 0 0
A Coruña
Country [17] 0 0
Spain
State/province [17] 0 0
Madrid
Country [18] 0 0
Taiwan
State/province [18] 0 0
Taipei City
Country [19] 0 0
Taiwan
State/province [19] 0 0
Taipei

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Odonate Therapeutics, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Joseph O'Connell, MD
Address 0 0
Odonate Therapeutics, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT03858972