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

Primary Purpose

Breast Cancer Recurrent, HER2/Neu-negative Carcinoma of Breast, Hormone Receptor Positive Malignant Neoplasm of Breast

Status

Completed

Phase

Phase 4

Locations

Germany

Study Type

Interventional

Intervention

Bevacizumab

Capecitabine

Everolimus

Exemestane

Patient questionaires

About this trial

This is an interventional other trial for Breast Cancer Recurrent focused on measuring breast cancer, advanced, inoperable, metastatic, HER2/neu-negative, hormone receptor positive, HR+, female, postmenopausal

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

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

Adult women (≥ 18 years of age)
. 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.
Pathologically confirmed HER2/neu-negative, ER/PR positive inoperable or metastatic adenocarcinoma of the breast
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)
No indication for other chemotherapeutic treatment including Taxanes or Anthracyclines
Measurable or non-measurable disease as per RECIST 1.1
Adequate bone marrow, liver and renal function (according to current SmPCs of both treatment regimens)
ECOG performance status 0-2
Fluent German (spoken and written) language

Exclusion Criteria:

Prior palliative cytotoxic chemotherapies
Prior exposure to mTOR-Inhibitors (prior treatment with exemestane is allowed)
Concomitant antihormonal therapies, other than study medication
Symptomatic visceral metastases (as deemed by the investigator)
Uncontrolled CNS metastases
Unstable skeletal metastases
Medically uncontrolled cardiovascular diseases (e.g. uncontrolled hypertension)
Medically uncontrolled diabetes mellitus
Severe hepatic impairment (Child-Pugh C)
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]
Known HIV infection or chronic hepatitis B or C or history of hepatitis B or C
Known dihydropyrimidine dehydrogenase (DPD) deficiency
Any other contraindications to the study drugs used or their excipients according to current SmPCs
Concomitant use of immunosuppressive agents or chronic use of systemic corticosteroids
Use of any other concomitant medication known to interfere with the study drugs
Use of concomitant medication known to interfere with the study results (e.g. hormonal therapy) during the whole study duration
Premenopausal patients
Pregnant or breast feeding patients
Participation in additional parallel interventional drug or device studies within four weeks before start of study.

Sites / Locations

iOMEDICO AG

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Arm A

Arm B

Arm Description

Bevacizumab plus Capecitabine (1st treatment phase) followed by Everolimus plus Exemestane (2nd treatment phase) Dosing (treatment cycle: 21days): 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) 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)

Everolimus plus Exemestane (1st treatment phase) followed by Bevacizumab plus Capecitabine (2nd treatment phase) Dosing (treatment cycle: 21days): Everolimus: 10 mg/day orally applied tablet --- Exemestane: 25 mg/day orally applied tablet 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)

Outcomes

Primary Outcome Measures

Patients' preference

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

Reasons for patients' preference

To evaluate reasons for preference as assessed by the patient preference questionnaire

Patient reported treatment satisfaction

To compare patient reported treatment satisfaction as assessed by the treatment satisfaction questionnaire in first- and second treatment phase

Quality of life

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

Progression free survival rate

To assess progression free survival rates after 12 weeks of therapy in first- (PFS rate 1) and second treatment phase (PFS rate 2)

Objective response rates and disease control rates based on tumor assessment (RECIST 1.1)

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

Safety and tolerability as measured by number of treatment-emergent adverse events (AEs) and clinical laboratory abnormalities

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)

Physicians' treatment preference

To determine physicians' treatment preference as assessed by the physician preference questionnaire

Progression free survival for first and second treatment phase

To explore progression free survival separately for each treatment phase

Overall survival

To explore overall survival for each treatment arm beginning from start of respective treatment phase until end of follow-up phase

Full Information

NCT ID

NCT02248571

First Posted

August 28, 2014

Last Updated

November 8, 2017

Sponsor

iOMEDICO AG

Collaborators

Arbeitsgemeinschaft fur Internistische Onkologie, Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT02248571

Brief Title

Patient Preference for Everolimus in Combination With Exemestane or Capecitabine in Combination With Bevacizumab

Acronym

IMPROVE

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

2. Study Status

Record Verification Date

November 2017

Overall Recruitment Status

Completed

Study Start Date

August 2014 (Actual)

Primary Completion Date

August 31, 2017 (Actual)

Study Completion Date

September 30, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

iOMEDICO AG

Collaborators

Arbeitsgemeinschaft fur Internistische Onkologie, Novartis Pharmaceuticals

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Other

Study Phase

Phase 4

Interventional Study Model

Crossover Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

85 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm A

Arm Type

Experimental

Arm Description

Arm Title

Arm B

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Bevacizumab

Other Intervention Name(s)

Avastin®

Intervention Description

administered as combined therapy with Capecitabine

Intervention Type

Drug

Intervention Name(s)

Capecitabine

Intervention Description

administered as combined therapy with Bevacizumab

Intervention Type

Drug

Intervention Name(s)

Everolimus

Other Intervention Name(s)

Afinitor®

Intervention Description

administered as combined therapy with Exemestane

Intervention Type

Drug

Intervention Name(s)

Exemestane

Intervention Description

administered as combined therapy with Everolimus

Intervention Type

Other

Intervention Name(s)

Patient questionaires

Other Intervention Name(s)

Papient reported outcome, Patients' preference

Intervention Description

Patients will fill out questionaires at four specific time points during study treatment to assess patient reported outcome and patients' preference

Primary Outcome Measure Information:

Title

Patients' preference

Description

Time Frame

After 12 weeks of second treatment phase or two weeks after early (< 12 weeks) treatment discontinuation

Secondary Outcome Measure Information:

Title

Reasons for patients' preference

Description

To evaluate reasons for preference as assessed by the patient preference questionnaire

Time Frame

After 12 weeks of second treatment phase or two weeks after early (< 12 weeks) treatment discontinuation

Title

Patient reported treatment satisfaction

Description

To compare patient reported treatment satisfaction as assessed by the treatment satisfaction questionnaire in first- and second treatment phase

Time Frame

After 12 weeks of first and second treatment phase or two weeks after early (< 12 weeks) treatment discontinuation of each treatment phase

Title

Quality of life

Description

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

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

Title

Progression free survival rate

Description

To assess progression free survival rates after 12 weeks of therapy in first- (PFS rate 1) and second treatment phase (PFS rate 2)

Time Frame

After 12 weeks of first and second treatment phase

Title

Objective response rates and disease control rates based on tumor assessment (RECIST 1.1)

Description

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

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)

Title

Safety and tolerability as measured by number of treatment-emergent adverse events (AEs) and clinical laboratory abnormalities

Description

Time Frame

From date of informed consent to +30 days from last application of study medication

Title

Physicians' treatment preference

Description

To determine physicians' treatment preference as assessed by the physician preference questionnaire

Time Frame

After 12 weeks of second treatment phase or two weeks after early (< 12 weeks) treatment discontinuation

Title

Progression free survival for first and second treatment phase

Description

To explore progression free survival separately for each treatment phase

Time Frame

Participants will be followed until progressive disease in boths treatment phases (expected 21 months in total)

Title

Overall survival

Description

To explore overall survival for each treatment arm beginning from start of respective treatment phase until end of follow-up phase

Time Frame

Participants will be followed until death (expected median of 24 months)

Other Pre-specified Outcome Measures:

Title

Relationship Quality of life scores / patient preference

Description

To explore relationship between QoL scores and patient preference (Exploratory objective)

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

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Written informed consent must be obtained prior to any study specific procedure. Adult women (≥ 18 years of age) . 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. Pathologically confirmed HER2/neu-negative, ER/PR positive inoperable or metastatic adenocarcinoma of the breast 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) No indication for other chemotherapeutic treatment including Taxanes or Anthracyclines Measurable or non-measurable disease as per RECIST 1.1 Adequate bone marrow, liver and renal function (according to current SmPCs of both treatment regimens) ECOG performance status 0-2 Fluent German (spoken and written) language Exclusion Criteria: Prior palliative cytotoxic chemotherapies Prior exposure to mTOR-Inhibitors (prior treatment with exemestane is allowed) Concomitant antihormonal therapies, other than study medication Symptomatic visceral metastases (as deemed by the investigator) Uncontrolled CNS metastases Unstable skeletal metastases Medically uncontrolled cardiovascular diseases (e.g. uncontrolled hypertension) Medically uncontrolled diabetes mellitus Severe hepatic impairment (Child-Pugh C) 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] Known HIV infection or chronic hepatitis B or C or history of hepatitis B or C Known dihydropyrimidine dehydrogenase (DPD) deficiency Any other contraindications to the study drugs used or their excipients according to current SmPCs Concomitant use of immunosuppressive agents or chronic use of systemic corticosteroids Use of any other concomitant medication known to interfere with the study drugs Use of concomitant medication known to interfere with the study results (e.g. hormonal therapy) during the whole study duration Premenopausal patients Pregnant or breast feeding patients Participation in additional parallel interventional drug or device studies within four weeks before start of study.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Thomas Decker, MD

Organizational Affiliation

practice based oncology office Ravensburg

Official's Role

Principal Investigator

Facility Information:

Facility Name

iOMEDICO AG

City

Freiburg

State/Province

Baden-Wuerttemberg

ZIP/Postal Code

79108

Country

Germany

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

22149876

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.

Results Reference

background

PubMed Identifier

24158787

Citation

Yardley DA, Noguchi S, Pritchard KI, Burris HA 3rd, Baselga J, Gnant M, Hortobagyi GN, Campone M, Pistilli B, Piccart M, Melichar B, Petrakova K, Arena FP, Erdkamp F, Harb WA, Feng W, Cahana A, Taran T, Lebwohl D, Rugo HS. Everolimus plus exemestane in postmenopausal patients with HR(+) breast cancer: BOLERO-2 final progression-free survival analysis. Adv Ther. 2013 Oct;30(10):870-84. doi: 10.1007/s12325-013-0060-1. Epub 2013 Oct 25. Erratum In: Adv Ther. 2014 Sep;31(9):1008-9.

Results Reference

background

PubMed Identifier

15681523

Citation

Miller KD, Chap LI, Holmes FA, Cobleigh MA, Marcom PK, Fehrenbacher L, Dickler M, Overmoyer BA, Reimann JD, Sing AP, Langmuir V, Rugo HS. Randomized phase III trial of capecitabine compared with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer. J Clin Oncol. 2005 Feb 1;23(4):792-9. doi: 10.1200/JCO.2005.05.098.

Results Reference

background

PubMed Identifier

21383283

Citation

Robert NJ, Dieras V, Glaspy J, Brufsky AM, Bondarenko I, Lipatov ON, Perez EA, Yardley DA, Chan SY, Zhou X, Phan SC, O'Shaughnessy J. RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol. 2011 Apr 1;29(10):1252-60. doi: 10.1200/JCO.2010.28.0982. Epub 2011 Mar 7.

Results Reference

background

PubMed Identifier

24687826

Citation

Escudier B, Porta C, Bono P, Powles T, Eisen T, Sternberg CN, Gschwend JE, De Giorgi U, Parikh O, Hawkins R, Sevin E, Negrier S, Khan S, Diaz J, Redhu S, Mehmud F, Cella D. Randomized, controlled, double-blind, cross-over trial assessing treatment preference for pazopanib versus sunitinib in patients with metastatic renal cell carcinoma: PISCES Study. J Clin Oncol. 2014 May 10;32(14):1412-8. doi: 10.1200/JCO.2013.50.8267. Epub 2014 Mar 31.

Results Reference

background

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Patient Preference for Everolimus in Combination With Exemestane or Capecitabine in Combination With Bevacizumab

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