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

• Sponsor: Odonate Therapeutics, Inc. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT03858972
• Collaborator: (none)
• Enrollment: 152
• Locations: 25
• Arm: 1
• Actual Duration (Months): 28.2
• Patients Per Site: 6.1
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: Tesetaxel; Drug: Capecitabine	Phase 2

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. 152 patients were enrolled, including 149 who received treatment. Patients are administered 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 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 efficacy endpoint is ORR as assessed by the IRC. The secondary efficacy endpoints are duration of response (DoR) as assessed by the IRC, progression-free survival (PFS) as assessed by the IRC, disease control rate (DCR) as assessed by the IRC and overall survival (OS). CONTESSA 2 also investigates the PK of tesetaxel.

Study Design

• Study Type: Interventional
• Actual Enrollment: 152 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Feb 5, 2019
• Actual Primary Completion Date: Jun 11, 2021
• Actual Study Completion Date: Jun 11, 2021

Arms and Interventions

Arm

Intervention/Treatment

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.

Drug: Tesetaxel; Tesetaxel plus reduced dose of capecitabine; Drug: Capecitabine; Reduced dose of capecitabine

Outcome Measures

Primary Outcome Measures

1. ORR as assessed by the IRC [Approximately 2.0-2.5 years]

Secondary Outcome Measures

1. DoR as assessed by the IRC [Approximately 2.0-2.5 years]

2. PFS as assessed by the IRC [Approximately 2.0-2.5 years]

3. DCR as assessed by the IRC [Approximately 2.0-2.5 years]

4. OS [Approximately 3.0-3.5 years]

5. Central nervous system (CNS) ORR as assessed by the CNS IRC in patients with CNS metastases at baseline [Approximately 2.0-2.5 years]

6. CNS DoR as assessed by the CNS IRC in patients with CNS metastases at baseline [Approximately 2.0-2.5 years]

7. 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 [Approximately 2.0-2.5 years]

8. CNS OS in patients with CNS metastases at baseline or a history of CNS metastases [Approximately 3.0-3.5 years]

Other Outcome Measures

1. Adverse events, including deaths and other serious adverse events [Approximately 3.0-3.5 years]

2. Incidence of clinical laboratory abnormalities (e.g., CBC, serum chemistry and coagulation testing) [Approximately 3.0-3.5 years]

3. Peak plasma concentration (Cmax) of tesetaxel [Approximately 2.0-2.5 years]

4. Area under the plasma concentration versus time curve (AUC) of tesetaxel [Approximately 2.0-2.5 years]

5. The effect of tesetaxel on capecitabine and 5-FU Cmax [Approximately 2.0-2.5 years]

6. The effect of tesetaxel on capecitabine and 5-FU AUC [Approximately 2.0-2.5 years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

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

2. 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.

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

4. 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

1. 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

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

3. 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)

4. 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

1. 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

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

2. 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, 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Innovative Clinical Research Institute	Whittier	California	United States	90603
2	Rocky Mountain Cancer Center	Lakewood	Colorado	United States	80228
3	Sarah Cannon Research Institute - Florida Cancer Specialists	Fort Myers	Florida	United States	33901
4	Florida Cancer Specialists and Research Institute	Saint Petersburg	Florida	United States	33705
5	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
6	New York Cancer and Blood Specialists	East Setauket	New York	United States	11733
7	West Cancer Center	Germantown	Tennessee	United States	38138
8	Texas Oncology - Baylor Charles A. Sammons Cancer Center	Dallas	Texas	United States	75246
9	Virginia Oncology Associates	Norfolk	Virginia	United States	23502
10	Border Medical Oncology	Albury	New South Wales	Australia	2640
11	Hopital Maisonneuve-Rosemont	Montréal		Canada	H1T 4B3
12	Center Hospitalier de Montreal CHUM McPeak Sirois	Montréal		Canada	H2X 3E4
13	CIUSSS de Centre-Ouest-de-l'Île-de-Montréal Jewish General Hospital	Montréal		Canada	H3T IE2
14	McGill University Health Center	Montréal		Canada	H4J 3J1
15	CHU de Quebec-University Laval	Québec		Canada	G1S 4L8
16	Centre Hospitalier Universitaire de Sherbrooke CIUSSS de lEstrie CHUS patyre	Sherbrooke		Canada	J1H 5N4
17	Kyungpook National University Hospital	Daegu		Korea, Republic of
18	National Cancer Center	Goyang		Korea, Republic of
19	Gangnam Severance Hospital	Seoul		Korea, Republic of	06273
20	Asan Medical Center	Seoul		Korea, Republic of
21	Ajou University Hospital	Suwon		Korea, Republic of
22	Hospital Teresa Herrera Materno-Infantil (CHUAC)	A Coruña		Spain	15006
23	Fundacion Jimenez Diaz	Madrid		Spain	28040
24	National Taiwan University Hospital	Taipei City		Taiwan
25	Koo Foundation Sun Yat-Sen Cancer Center	Taipei		Taiwan

Sponsors and Collaborators

• Odonate Therapeutics, Inc.

Investigators

• Study Director: Joseph O'Connell, MD, Odonate Therapeutics, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Odonate Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT03858972
• Other Study ID Numbers: ODO-TE-B201
• First Posted: Mar 1, 2019
• Last Update Posted: Jul 30, 2021
• Last Verified: Jul 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Odonate Therapeutics, Inc.: 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
• Additional relevant MeSH terms: Breast Neoplasms; Capecitabine

Study Results

No Results Posted as of Jul 30, 2021