Patient Preference for Everolimus in Combination With Exemestane or Capecitabine in Combination With Bevacizumab (IMPROVE)

iOMEDICO

Status and phase: Completed; Phase 4

Conditions: Hormone Receptor Positive Malignant Neoplasm of Breast; Breast Cancer Recurrent; HER2/Neu-negative Carcinoma of Breast

Treatments: Drug: Bevacizumab; Other: Patient questionaires; Drug: Everolimus; Drug: Capecitabine; Drug: Exemestane

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT02248571

iOM-12293

Details and patient eligibility

About

This is a clinical trial with a crossover design to determine patients' preference for capecitabine in combination with bevacizumab or everolimus in combination with exemestane for advanced breast cancer patients and to evaluate, if any combination is associated with a better quality of life.

To identify patients' preference for either therapy in this trial, patients without disease progression or other reasons for early discontinuation will be asked for their treatment preference and their treatment satisfaction. To correlate patients' preference with other patient reported outcomes (PROs), quality of life (QoL) will be assessed at baseline and throughout the study, using dedicated questionnaires.

With similarly active treatment options, it is of utmost importance to identify the treatment that has the least negative impact on the patients' quality of life.

Enrollment: 85 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Written informed consent must be obtained prior to any study specific procedure.

1. Adult women (≥ 18 years of age)

2. . Postmenopausal status

   The investigator must confirm postmenopausal status. Postmenopausal status is defined either by:

   • Age ≥ 55 years and one year or more of amenorrhea
   • Age < 55 years and one year or more of amenorrhea and postmenopausal levels of follicle stimulating hormone (FSH) and Luteinizing hormone (LH) per local institutional standards
   • Prior hysterectomy and has postmenopausal levels of FSH and LH per local institutional standards
   • Surgical menopause with bilateral oophorectomy
   • For women with therapy-induced amenorrhea, oophorectomy or serial measurements of FSH and / or estradiol are needed to ensure postmenopausal status.

   Note: Ovarian radiation or treatment with a luteinizing hormone-releasing hormone (LH-RH) agonist (goserelin acetate or leuprolide acetate) is not permitted for induction of ovarian suppression.

3. Pathologically confirmed HER2/neu-negative, ER/PR positive inoperable or metastatic adenocarcinoma of the breast

4. Indication for systemic palliative targeted therapy / first line chemotherapy after failure of at least one non-steroidal aromatase inhibitor therapy at any time during the disease course (no restriction regarding the number of previous endocrine lines)

5. No indication for other chemotherapeutic treatment including Taxanes or Anthracyclines

6. Measurable or non-measurable disease as per RECIST 1.1

7. Adequate bone marrow, liver and renal function (according to current SmPCs of both treatment regimens)

8. ECOG performance status 0-2

9. Fluent German (spoken and written) language

Exclusion criteria

1. Prior palliative cytotoxic chemotherapies

2. Prior exposure to mTOR-Inhibitors (prior treatment with exemestane is allowed)

3. Concomitant antihormonal therapies, other than study medication

4. Symptomatic visceral metastases (as deemed by the investigator)

5. Uncontrolled CNS metastases

6. Unstable skeletal metastases

7. Medically uncontrolled cardiovascular diseases (e.g. uncontrolled hypertension)

8. Medically uncontrolled diabetes mellitus

9. Severe hepatic impairment (Child-Pugh C)

10. Inadequate organ function as specified below:

    • Hemoglobin < 9.0 g/dl
    • Absolute neutrophil count (ANC) <1,5 x109/L
    • Platelets <100 x109/L
    • Creatinine clearance < 30ml/min [Cockcroft and Gault]

11. Known HIV infection or chronic hepatitis B or C or history of hepatitis B or C

12. Known dihydropyrimidine dehydrogenase (DPD) deficiency

13. Any other contraindications to the study drugs used or their excipients according to current SmPCs

14. Concomitant use of immunosuppressive agents or chronic use of systemic corticosteroids

15. Use of any other concomitant medication known to interfere with the study drugs

16. Use of concomitant medication known to interfere with the study results (e.g. hormonal therapy) during the whole study duration

17. Premenopausal patients

18. Pregnant or breast feeding patients

19. Participation in additional parallel interventional drug or device studies within four weeks before start of study.

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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85 participants in 2 patient groups

Arm A

Experimental group

Description:

Bevacizumab plus Capecitabine (1st treatment phase) followed by Everolimus plus Exemestane (2nd treatment phase) Dosing (treatment cycle: 21days): 1. Capecitabine: 1000 mg/m2 orally applied twice daily as combined 150 mg and 500 mg tablets on days 1 to 14 of each 21-day cycle, followed by a seven day rest period (i.e. off-treatment) --- Bevacizumab: 15 mg/kg intravenously applied once every three weeks (i.e. 5 mg/kg/wk dose equivalent) 2. Everolimus: 10 mg/day orally applied tablet --- Exemestane: 25 mg/day orally applied tablet Patient questionaires to assess patient reported outcome and patients' preference will be completed at four specific time points during study treatment (two timepoints in each treatment phase)

Treatment:

Drug: Exemestane

Drug: Everolimus

Other: Patient questionaires

Drug: Bevacizumab

Drug: Capecitabine

Arm B

Experimental group

Description:

Everolimus plus Exemestane (1st treatment phase) followed by Bevacizumab plus Capecitabine (2nd treatment phase) Dosing (treatment cycle: 21days): 1. Everolimus: 10 mg/day orally applied tablet --- Exemestane: 25 mg/day orally applied tablet 2. Capecitabine: 1000 mg/m2 orally applied twice daily as combined 150 mg and 500 mg tablets on days 1 to 14 of each 21-day cycle, followed by a seven day rest period (i.e. off-treatment) --- Bevacizumab: 15 mg/kg intravenously applied once every three weeks (i.e. 5 mg/kg/wk dose equivalent) Patient questionaires to assess patient reported outcome and patients' preference will be completed at four specific time points during study treatment (two timepoints in each treatment phase)

Treatment:

Drug: Exemestane

Drug: Everolimus

Other: Patient questionaires

Drug: Bevacizumab

Drug: Capecitabine