Clinical Trials /

Study on Androgen Receptor and Triple Negative Breast Cancer

NCT03383679

Description:

This is a multicenter uncontrolled, open-label, prospective, non-comparative randomized, phase II study. Patients will be randomized between darolutamide in Arm n°1 (two-stage Simon's design) and capecitabine in Arm n°2 with two patients randomized in Arm n°1 for one patient randomized in Arm n°2. The trial population is composed of women over 18 years old with triple-negative and androgen receptor positive, locally recurrent (unresectable) or metastatic breast cancer.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study on Androgen Receptor and Triple Negative Breast Cancer
  • Official Title: A Randomized Phase 2 Study in Patients With Triple-negative Androgen Receptor Positive Locally Recurrent (Unresectable) or Metastatic Breast Cancer Treated With Darolutamide or Capecitabine

Clinical Trial IDs

  • ORG STUDY ID: UC-0140/1711 - UCBG3-06
  • NCT ID: NCT03383679

Conditions

  • Breast Cancer Female
  • Triple Negative and Androgen Receptor Positive

Interventions

DrugSynonymsArms
DarolutamideArm 1 Darolutamide
CapecitabineArm 2 Capecitabine

Purpose

This is a multicenter uncontrolled, open-label, prospective, non-comparative randomized, phase II study. Patients will be randomized between darolutamide in Arm n°1 (two-stage Simon's design) and capecitabine in Arm n°2 with two patients randomized in Arm n°1 for one patient randomized in Arm n°2. The trial population is composed of women over 18 years old with triple-negative and androgen receptor positive, locally recurrent (unresectable) or metastatic breast cancer.

Trial Arms

NameTypeDescriptionInterventions
Arm 1 DarolutamideExperimentalDarolutamib: 600 mg (2 tablets of 300 mg) twice daily with food (equivalent to a daily dose of 1200 mg) will be administered orally, continuously until disease progression
  • Darolutamide
Arm 2 CapecitabineOtheraccording to the 3rd ESO-ESMO international consensus guidelines for advanced breast cancer (ABC3) capecitabine monotherapy is one of the recommended options even in first line (Cardoso et al, 2017). According to each center policy (minimum 1000 mg/m²) twice daily for 2 weeks followed by 1-week rest period, until progression or unacceptable toxicity
  • Capecitabine

Eligibility Criteria

        Inclusion Criteria:

          1. Woman, ≥ 18 years old;

          2. Histologically confirmed locally recurrent (unresectable) or metastatic breast cancer;

          3. Triple negative breast cancer:

             Estrogen receptor (ER)-negative and Progesterone receptor (PgR)-negative, as defined
             by a < 10 % tumor stained cells by immunohistochemistry (IHC); HER2 negative status
             (i.e. IHC score 0 or 1+, or IHC score 2+ and FISH/SISH/CISH negative), confirmed
             centrally before inclusion with FFPE tissue from the primary tumour;

          4. Androgen receptor (AR)-positive, as defined centrally by a ≥ 10% tumor stained cells
             by IHC Note: AR assessment by local pathologist before inclusion is not mandatory;

          5. Patients with a relapse or progressive disease 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; Note: subject must not have received any growth factor within 4
             weeks or blood transfusion within 7 days of the hematology laboratory sample obtained
             at screening)

         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. 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);

         13. Cardiac ejection fraction ≥50% measured by MUGA or ECHO done within 4 weeks before
             inclusion;

         14. For premenopausal patients, patient agreeing to use effective contraception during and
             for ≥ 6 months after completion of study treatment;

         15. Patient able to comply with the protocol;

         16. Patient must have signed a written informed consent form prior to any study specific
             procedures;

         17. Patient must be affiliated to a Social Health Insurance.

        Exclusion Criteria:

          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:

               1. NYHA class III-IV congestive heart failure

               2. Stroke, unstable angina pectoris or myocardial infarction within the past 6
                  months

               3. Severe valvular heart disease

               4. 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. Active or uncontrolled autoimmune disease requiring concurrent corticosteroid therapy;

          9. Any gastrointestinal disorder interfering with absorption of the study drug;

         10. Difficulties with swallowing tablets;

         11. An active viral hepatitis, known human immunodeficiency virus infection with
             detectable viral load, or chronic liver disease requiring treatment;

         12. Previous treatment with second-generation AR inhibitors such as enzalutamide, ARN-509,
             ODM-201, other investigational AR inhibitors CYP17 enzyme inhibitor such as
             abiraterone, capecitabine…

         13. Patients with known of deficit of dihydropyrimidine dehydrogenase (DPD) activity (see
             section 4.4) or in case of hypersensitivity to capecitabine or to any of its
             excipients or to fluorouracil

         14. Prior anticancer therapy, including radiotherapy, endocrine therapy, immunotherapy;
             chemotherapy within the last 3 weeks (6 weeks for nitrosoureas and mitomycin C), or
             other investigational agents; concurrent palliative radiotherapy is allowed;

         15. Previous (within 28 days before the start of study drug or 5 half-lives of the
             investigational treatment of the previous study, whichever is longer) or concomitant
             participation in another clinical study with investigational medicinal product;

         16. Pregnant women, women who are likely to become pregnant or are breast-feeding;

         17. 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;

         18. Patients with history of non-compliance to medical regimens or unwilling or unable to
             comply with the protocol;

         19. Individual deprived of liberty or placed under the authority of a tutor.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:clinical benefit rate
Time Frame:at 16 weeks
Safety Issue:
Description: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 Outcome Measures

Measure:clinical benefit rate
Time Frame:at 24 weeks
Safety Issue:
Description:Clinical benefit rate (CBR24)
Measure:Objective response rate
Time Frame:at 16 and 24 weeks
Safety Issue:
Description:Objective response rate (ORR)
Measure:Duration of overall response
Time Frame:at 16 and 24 weeks
Safety Issue:
Description:Duration of overall response (DoR)
Measure:Overall survival
Time Frame:at 1 and 2 years
Safety Issue:
Description:Overall survival (OS)
Measure:Progression-free survival
Time Frame:at 1 and 2 years
Safety Issue:
Description:Progression-free survival (PFS)
Measure:Safety: Evaluation of toxicity in each arm according to CTCAE V4.03
Time Frame:From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Safety Issue:
Description:Evaluation of toxicity in each arm according to CTCAE V4.03

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:UNICANCER

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