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

NCT03858972 | Terminated Phase 2 FDA Drug

• 1 other identifier: ODO-TE-B201
• Study Type: interventional
• Target: 152
• Locations: 6 countries
• Sites: 25

Brief Summary

CONTESSA 2 is a multinational, multicenter, Phase 2 study of tesetaxel in patients with HER2 negative, HR positive, locally advanced or metastatic breast cancer (LA/MBC) not previously treated with a taxane. 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). 152 patients were enrolled.

Conditions

Breast Cancer

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

Outcome Measures

Primary Outcomes (1)

• ORR as assessed by the IRC

  Approximately 2.0-2.5 years

Secondary Outcomes (8)

• DoR as assessed by the IRC

  Approximately 2.0-2.5 years

• PFS as assessed by the IRC

  Approximately 2.0-2.5 years

• DCR as assessed by the IRC

  Approximately 2.0-2.5 years

• OS

  Approximately 3.0-3.5 years

• Central nervous system (CNS) ORR as assessed by the CNS IRC in patients with CNS metastases at baseline

  Approximately 2.0-2.5 years

Other Outcomes (6)

• Adverse events, including deaths and other serious adverse events

  Approximately 3.0-3.5 years

• Incidence of clinical laboratory abnormalities (e.g., CBC, serum chemistry and coagulation testing)

  Approximately 3.0-3.5 years

• Peak plasma concentration (Cmax) of tesetaxel

  Approximately 2.0-2.5 years

Study Arms (1)

Tesetaxel (oral) and capecitabine (oral)

EXPERIMENTAL

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.

Drug: Tesetaxel; Drug: Capecitabine

Interventions

Tesetaxel DRUG

Tesetaxel plus reduced dose of capecitabine

Tesetaxel (oral) and capecitabine (oral)

Capecitabine DRUG

Reduced dose of capecitabine

Tesetaxel (oral) and capecitabine (oral)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female or male patients at least 18 years of age
• Histologically or cytologically confirmed breast cancer
• 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
• HR (ER and/or PgR) positive disease based on local testing: ASCO/CAP guidelines should be utilized for assessing HR status
• 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

You may not qualify if:

• Two or more prior chemotherapy regimens for advanced disease
• Prior treatment with a taxane at any dose
• Prior treatment with capecitabine at any dose
• Current evidence of leptomeningeal disease
• 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
• 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.
• Active hepatitis B or active hepatitis C infection
• 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.
• Presence of neuropathy \> Grade 1 per NCI CTCAE version 5.0
• 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
• Major surgery ≤ 28 days prior to the date of Enrollment; patient must have complete recovery from surgery
• 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)
• History of hypersensitivity or unexpected reactions to capecitabine, fluoropyrimidine agents or any of their ingredients
• 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.
• Pregnant or breastfeeding

Sponsors & Collaborators

• Odonate Therapeutics, Inc.: lead

Study Sites (25)

Innovative Clinical Research Institute

Whittier, California, 90603, United States

Location

Rocky Mountain Cancer Center

Lakewood, Colorado, 80228, United States

Location

Sarah Cannon Research Institute - Florida Cancer Specialists

Fort Myers, Florida, 33901, United States

Location

Florida Cancer Specialists and Research Institute

St. Petersburg, Florida, 33705, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

New York Cancer and Blood Specialists

East Setauket, New York, 11733, United States

Location

West Cancer Center

Germantown, Tennessee, 38138, United States

Location

Texas Oncology - Baylor Charles A. Sammons Cancer Center

Dallas, Texas, 75246, United States

Location

Virginia Oncology Associates

Norfolk, Virginia, 23502, United States

Location

Border Medical Oncology

Albury, New South Wales, 2640, Australia

Location

Hopital Maisonneuve-Rosemont

Montreal, H1T 4B3, Canada

Location

Center Hospitalier de Montreal CHUM McPeak Sirois

Montreal, H2X 3E4, Canada

Location

CIUSSS de Centre-Ouest-de-l'Île-de-Montréal Jewish General Hospital

Montreal, H3T IE2, Canada

Location

McGill University Health Center

Montreal, H4J 3J1, Canada

Location

CHU de Quebec-University Laval

Québec, G1S 4L8, Canada

Location

Centre Hospitalier Universitaire de Sherbrooke CIUSSS de lEstrie CHUS patyre

Sherbrooke, J1H 5N4, Canada

Location

Kyungpook National University Hospital

Daegu, South Korea

Location

National Cancer Center

Goyang, South Korea

Location

Gangnam Severance Hospital

Seoul, 06273, South Korea

Location

Asan Medical Center

Seoul, South Korea

Location

Ajou University Hospital

Suwon, South Korea

Location

Hospital Teresa Herrera Materno-Infantil (CHUAC)

A Coruña, 15006, Spain

Location

Fundacion Jimenez Diaz

Madrid, 28040, Spain

Location

Koo Foundation Sun Yat-Sen Cancer Center

Taipei, Taiwan

Location

National Taiwan University Hospital

Taipei, Taiwan

Location

MeSH Terms

Conditions

Breast Neoplasms; Neoplasm Metastasis

Interventions

tesetaxel; Capecitabine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Joseph O'Connell, MD

  Odonate Therapeutics, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 26, 2019
• First Posted: March 1, 2019
• Study Start: February 5, 2019
• Primary Completion: June 11, 2021
• Study Completion: June 11, 2021
• Last Updated: July 30, 2021

Record last verified: 2021-07

Locations

TW (2); AU (1); CA (6); KR (5); US (9); ES (2)