Clinical trial NCT02248571: Patient Preference for Everolimus in Combination With Exemestane or Capecitabine in Combination With Bevacizumab
Official title: An Open Label, randomIzed Controlled Prospective Multicenter Two Arm Phase IV Trial to Determine Patient Preference for Everolimus in Combination With Exemestane or Capecitabine in Combination With Bevacizumab for Advanced (Inoperable or Metastatic) HER2-negative Hormone Receptor Positive Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Breast Cancer Recurrent
HER2/Neu-negative Carcinoma of Breast
Hormone Receptor Positive Malignant Neoplasm of Breast
Keywords: breast cancer
advanced
inoperable
metastatic
HER2/neu-negative
hormone receptor positive
HR+
female
postmenopausal
Lead sponsor: iOMEDICO AG
Sponsor class: INDUSTRY
Collaborators: name: Arbeitsgemeinschaft fur Internistische Onkologie
name: Novartis Pharmaceuticals
First posted: 2014-09-25
Enrollment: 85
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Patients' preference
timeFrame: After 12 weeks of second treatment phase or two weeks after early (< 12 weeks) treatment discontinuation
Secondary outcomes:
measure: Reasons for patients' preference
timeFrame: After 12 weeks of second treatment phase or two weeks after early (< 12 weeks) treatment discontinuation
measure: Patient reported treatment satisfaction
timeFrame: After 12 weeks of first and second treatment phase or two weeks after early (< 12 weeks) treatment discontinuation of each treatment phase
measure: Quality of life
timeFrame: At baseline and after 12 weeks of first and second treatment phase or two weeks after early (< 12 weeks) treatment discontinuation of each treatment phase
measure: Progression free survival rate
timeFrame: After 12 weeks of first and second treatment phase
measure: Objective response rates and disease control rates based on tumor assessment (RECIST 1.1)
timeFrame: Participants will be followed for the whole duration of first phase therapy, with an expected average of 12 months, plus 3 months of second phase therapy (15 months in total)
measure: Safety and tolerability as measured by number of treatment-emergent adverse events (AEs) and clinical laboratory abnormalities
timeFrame: From date of informed consent to +30 days from last application of study medication
measure: Physicians' treatment preference
timeFrame: After 12 weeks of second treatment phase or two weeks after early (< 12 weeks) treatment discontinuation
measure: Progression free survival for first and second treatment phase
timeFrame: Participants will be followed until progressive disease in boths treatment phases (expected 21 months in total)
measure: Overall survival
timeFrame: Participants will be followed until death (expected median of 24 months)
Other outcomes:
measure: Relationship Quality of life scores / patient preference
timeFrame: At baseline and after 12 weeks of first and second treatment phase or two weeks after early (< 12 weeks) treatment discontinuation of each treatment phase
Locations:
city: Freiburg
country: Germany
facility: iOMEDICO AG
state: Baden-Wuerttemberg
Study officials:
affiliation: practice based oncology office Ravensburg
name: Thomas Decker, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Baselga J, Campone M, Piccart M, Burris HA 3rd, Rugo HS, Sahmoud T, Noguchi S, Gnant M, Pritchard KI, Lebrun F, Beck JT, Ito Y, Yardley D, Deleu I, Perez A, Bachelot T, Vittori L, Xu Z, Mukhopadhyay P, Lebwohl D, Hortobagyi GN. Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N Engl J Med. 2012 Feb 9;366(6):520-9. doi: 10.1056/NEJMoa1109653. Epub 2011 Dec 7.
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