START : Study on Androgen Receptor and Triple Negative Breast Cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Unicancer

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

14 Mar 2018 → ongoing

Decision date (initial)

2024-08-27

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

BAYER

External identifiers

EU CT number

2024-516638-36-00

EudraCT number

2017-002284-18

ClinicalTrials.gov

NCT03383679

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

The primary objective is to evaluate the antitumour activity of darolutamide or capecitabine in each arm among patients with triple-negative androgen receptor positive advanced/metastatic breast cancer, as measured by the clinical benefit rate at 16 weeks.

Secondary objectives 6

1. Efficacy : Clinical benefit rate at 24 weeks: CR, PR or SD at 24 weeks
2. Efficacy : Objective response rate (ORR) at 16 and 24 weeks
3. Efficacy : Duration of overall response (DoR) at 16 and 24 weeks
4. Efficacy : Overall survival (OS) at 1 and 2 years
5. Efficacy : Progression-free survival (PFS) at 1 and 2 years
6. Safety : Tolerance and safety.

Conditions and MedDRA coding

Triple-negative androgen receptor positive (molecular apocrine-like HER2-negative subtype) locally recurrent (unresectable) or metastatic breast cancer.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 18

1. Woman ≥ 18 years old;
2. Histologically confirmed locally recurrent (unresectable) or metastatic breast cancer;
3. Triple-negative breast cancer
4. Androgen receptor (AR)-positive, as defined centrally by a ≥ 10% tumor stained cells by IHC
5. Patients with a relapse should be chemotherapy naïve or have received a maximum of one line of chemotherapy for advanced disease (providing they are not presenting with life-threatening metastasis); patients could have received adjuvant or neo-adjuvant therapy;
6. In the exceptional situation of pre-menopausal patient, the addition of a LHRH analog is recommended (androgens might act as an estrogen antagonist in premenopausal patients);
7. Presence of measurable or evaluable disease according to RECIST v1.1;
8. ECOG ≤ 1;
9. Normal hematological function: ANC ≥ 1.500/mm3; platelets count ≥ 100.000/mm3; hemoglobin > 10 g/dL;
10. Normal hepatic function: total bilirubin ≤ 1.5 upper normal limit (UNL) unless this increase is due to a known Gilbert's disease; ASAT and ALAT ≤ 2.5 UNL (or ≤ 5 UNL in case of hepatic metastasis);
11. Creatinine clearance (MDRD formula) ≥ 50 mL/min;
12. Uracilemia< 16 ng/ml
13. Systolic blood pressure (BP) < 160 mm Hg and diastolic BP < 95 mm Hg, as documented on day of registration/consent (Hypertension allowed provided it is currently controlled);
14. Cardiac ejection fraction ≥50% measured by MUGA or ECHO done within 4 weeks before inclusion;
15. For premenopausal patients, patient agreeing to use effective contraception during and for ≥ 6 months after completion of study treatment;
16. Patient able to comply with the protocol;
17. Patient must have signed a written informed consent form prior to any study specific procedures;
18. Patient must be affiliated to a Social Health Insurance.

Exclusion criteria 18

1. HER2-positive status (positivity defined as IHC3+ and/or FISH amplification >2);
2. Other concurrent malignancies, except adequately treated cone-biopsied in situ carcinoma of the cervix or basal cell or squamous cell carcinoma of the skin; patients who have undergone potentially curative therapy for a prior malignancy are eligible provided there is no evidence of disease for ≥ 5 years and patient is deemed to be at low risk for recurrence;
3. Active brain metastases or leptomeningeal disease; history of brain metastases allowed provided lesions are stable for at least 3 months as documented by head CT scan or MRI of the brain.
4. Non-malignant systemic disease, including active infection or concurrent serious illness that would make the patient a high medical risk;
5. Significant cardiovascular disease, including any of the following: a) NYHA class III-IV congestive heart failure b) Stroke, unstable angina pectoris, or myocardial infarction within the past 6 months c) Severe valvular heart disease d) Ventricular arrhythmia requiring treatment;
6. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not be included;
7. Persistent toxicities grade ≥ 2 from any cause, except chemotherapy-induced alopecia and Grade 2 peripheral neuropathy;
8. Any gastrointestinal disorder interfering with absorption of the study drug;
9. Difficulties with swallowing tablets;
10. An active viral hepatitis, known human immunodeficiency virus infection with detectable viral load, or chronic liver disease requiring treatment;
11. PREVIOUS TREATMENT IN THE METASTATIC SETTING: Previous treatment with: capecitabine (MET SETTING), first generation (bicalutamide) or second–generation AR inhibitors (enzalutamide, ARN–509, darolutamide) or other investigational AR inhibitors CYP17 enzyme inhibitor such as abiraterone (capecitabine in the adjuvant setting is allowed provided the last administration was at least ≥12 months prior to study entry)
12. Patients with known deficit of dihydropyrimidine dehydrogenase (DPD) activity; or in case of hypersensitivity to capecitabine or to any of its excipients or to fluorouracil;
13. Prior anticancer therapy within the last 3 weeks including radiotherapy, endocrine therapy, immunotherapy; chemotherapy (6 weeks for nitrosoureas and mitomycin C), or other investigational agents; concurrent palliative radiotherapy is allowed;
14. Concurrent enrolment in another clinical trial in which investigational therapies are administered;
15. Pregnant women, women who are likely to become pregnant or are breast-feeding;
16. Patients with any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule. Those conditions should be discussed with the patient before registration in the trial;
17. Patients with history of non-compliance to medical regimens or unwilling or unable to comply with the protocol;
18. Individual deprived of liberty or placed under the authority of a tutor.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. For each arm (Arm n°1: darolutamide / Arm n°2: capecitabine): The primary endpoint is based on clinical benefit rate at 16 weeks. The clinical benefit rate (CBR) is the measurement of all patients who have a complete response (CR), partial response (PR) or stable disease (SD) at 16 weeks (CBR16) according to RECIST v1.1

Secondary endpoints 6

1. Efficacy : Clinical benefit rate at 24 weeks (CBR24)
2. Efficacy: Objective response rate (ORR) at 16 and 24 weeks: The Objective response is defined as complete response (CR) or partial response (PR) according to RECIST v1.1.
3. Efficacy: Duration of overall response (DoR) at 16 and 24 weeks: The DoR is defined as the time from documentation of tumour response (CR/PR) to disease progression, according to RECIST v1.1.
4. Efficacy: Overall Survival (OS) at 1 and 2 years: The OS is defined as the time from the first administration of treatment to death from any cause.
5. Efficacy: Progression-free survival (PFS) at 1 and 2 years: The PFS is defined as the time from the first administration of treatment to progression or death of any cause, whichever occurs first.
6. Safety: Evaluation of Toxicity in each arm Safety will be evaluated by type, frequency and severity of adverse drug reactions according to NCI-CTC (v4.03): In order to be considered evaluable for toxicity, patients should have received at least one dose of treatment.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Unicancer

Sponsor organisation

Unicancer

Address

101 Rue De Tolbiac

City

Paris

Postcode

75013

Country

France

Scientific contact point

Organisation

Unicancer

Contact name

Nourredine AIT RAHMOUNE

Public contact point

Organisation

Unicancer

Contact name

Nourredine AIT RAHMOUNE

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications