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

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ClinicalTrials.gov Identifier: NCT02248571
Recruitment Status : Completed
First Posted : September 25, 2014
Last Update Posted : November 13, 2017
Sponsor:
Collaborators:
Arbeitsgemeinschaft fur Internistische Onkologie
Novartis Pharmaceuticals
Information provided by (Responsible Party):
iOMEDICO AG

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.


Condition or disease Intervention/treatment Phase
Breast Cancer Recurrent HER2/Neu-negative Carcinoma of Breast Hormone Receptor Positive Malignant Neoplasm of Breast Drug: Bevacizumab Drug: Capecitabine Drug: Everolimus Drug: Exemestane Other: Patient questionaires Phase 4

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 85 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Other
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
Actual Study Start Date : August 2014
Actual Primary Completion Date : August 31, 2017
Actual Study Completion Date : September 30, 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Arm A

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)

Drug: Bevacizumab
administered as combined therapy with Capecitabine
Other Name: Avastin®

Drug: Capecitabine
administered as combined therapy with Bevacizumab

Drug: Everolimus
administered as combined therapy with Exemestane
Other Name: Afinitor®

Drug: Exemestane
administered as combined therapy with Everolimus

Other: Patient questionaires
Patients will fill out questionaires at four specific time points during study treatment to assess patient reported outcome and patients' preference
Other Names:
  • Papient reported outcome
  • Patients' preference

Experimental: Arm B

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)

Drug: Bevacizumab
administered as combined therapy with Capecitabine
Other Name: Avastin®

Drug: Capecitabine
administered as combined therapy with Bevacizumab

Drug: Everolimus
administered as combined therapy with Exemestane
Other Name: Afinitor®

Drug: Exemestane
administered as combined therapy with Everolimus

Other: Patient questionaires
Patients will fill out questionaires at four specific time points during study treatment to assess patient reported outcome and patients' preference
Other Names:
  • Papient reported outcome
  • Patients' preference




Primary Outcome Measures :
  1. Patients' preference [ Time Frame: After 12 weeks of second treatment phase or two weeks after early (< 12 weeks) treatment discontinuation ]

    Patients' preference of the two treatment combinations capecitabine plus bevacizumab or everolimus in combination with exemestane after failure of standard antihormonal therapy in patients with advanced (inoperable or metastatic) HER2/neu-negative hormone receptor positive breast cancer.

    The preference will be ascertained using the patient preference questionnaire.



Secondary Outcome Measures :
  1. Reasons for patients' preference [ Time Frame: After 12 weeks of second treatment phase or two weeks after early (< 12 weeks) treatment discontinuation ]
    To evaluate reasons for preference as assessed by the patient preference questionnaire

  2. Patient reported treatment satisfaction [ Time Frame: After 12 weeks of first and second treatment phase or two weeks after early (< 12 weeks) treatment discontinuation of each treatment phase ]
    To compare patient reported treatment satisfaction as assessed by the treatment satisfaction questionnaire in first- and second treatment phase

  3. Quality of life [ Time Frame: 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 ]
    To investigate differences in quality of life by the European Organization for Research and Treatment of Cancer quality of life questionnaire 30 (EORTC QLQ-C30) and EORTC QLQ-FA13 questionnaire

  4. Progression free survival rate [ Time Frame: After 12 weeks of first and second treatment phase ]
    To assess progression free survival rates after 12 weeks of therapy in first- (PFS rate 1) and second treatment phase (PFS rate 2)

  5. Objective response rates and disease control rates based on tumor assessment (RECIST 1.1) [ Time Frame: 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) ]
    To assess clinical benefit by determining objective response rates and disease control rates based on tumor assessment as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria

  6. Safety and tolerability as measured by number of treatment-emergent adverse events (AEs) and clinical laboratory abnormalities [ Time Frame: From date of informed consent to +30 days from last application of study medication ]
    To evaluate safety and tolerability throughout the study according to Common Toxicity Criteria for Adverse Effects (CTCAE) 4.03 criteria, including clinical laboratory (grades 3 or 4 - separately for hematology and biochemistry) and number of treatment-emergent AEs (safety data for pre- and post-treatment periods will be listed separately)

  7. Physicians' treatment preference [ Time Frame: After 12 weeks of second treatment phase or two weeks after early (< 12 weeks) treatment discontinuation ]
    To determine physicians' treatment preference as assessed by the physician preference questionnaire

  8. Progression free survival for first and second treatment phase [ Time Frame: Participants will be followed until progressive disease in boths treatment phases (expected 21 months in total) ]
    To explore progression free survival separately for each treatment phase

  9. Overall survival [ Time Frame: Participants will be followed until death (expected median of 24 months) ]
    To explore overall survival for each treatment arm beginning from start of respective treatment phase until end of follow-up phase


Other Outcome Measures:
  1. Relationship Quality of life scores / patient preference [ Time Frame: 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 ]
    To explore relationship between QoL scores and patient preference (Exploratory objective)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02248571


Locations
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Germany
iOMEDICO AG
Freiburg, Baden-Wuerttemberg, Germany, 79108
Sponsors and Collaborators
iOMEDICO AG
Arbeitsgemeinschaft fur Internistische Onkologie
Novartis Pharmaceuticals
Investigators
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Principal Investigator: Thomas Decker, MD practice based oncology office Ravensburg

Publications:

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Responsible Party: iOMEDICO AG
ClinicalTrials.gov Identifier: NCT02248571     History of Changes
Other Study ID Numbers: iOM-12293
First Posted: September 25, 2014    Key Record Dates
Last Update Posted: November 13, 2017
Last Verified: November 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by iOMEDICO AG:
breast cancer
advanced
inoperable
metastatic
HER2/neu-negative
hormone receptor positive
HR+
female
postmenopausal
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Sirolimus
Bevacizumab
Capecitabine
Everolimus
Exemestane
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Hormones, Hormone Substitutes, and Hormone Antagonists
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors