Everolimus Beyond Progress for Patients Who Had Progress Under Everolimus and Exemestane (Evelyn)

This study has been terminated.
(Study was stopped terminated early due to low recruitment.)
Sponsor:
Collaborator:
Novartis
Information provided by (Responsible Party):
German Breast Group
ClinicalTrials.gov Identifier:
NCT01773460
First received: January 15, 2013
Last updated: July 25, 2014
Last verified: August 2013
  Purpose

Everolimus will be given to patients with metastatic breast cancer who already has a progress taking Everolimus but with a change in the endocrine treatment.


Condition Intervention Phase
Metastatic Breast Cancer
Drug: Everolimus
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Multicenter Randomized, Double Blind, Placebo- Controlled, Phase II Study to Compare Endocrine Treatment Alone Versus Endocrine Treatment With Everolimus in Patients With HR+/HER2- Metastatic Breast Cancer and Progression After Previous Treatment With Exemestane and Everolimus

Resource links provided by NLM:


Further study details as provided by German Breast Group:

Primary Outcome Measures:
  • progression free survival [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    comparison of progression free survival between the two arms: with Everolimus or with Everolimus-placebo


Secondary Outcome Measures:
  • overall survival [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    comparison of the overall survival between the 2 arms

  • clinical benefit Rate(CBR) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    Clinical Benefit Rate (CBR) is defined as all patients with a complete, partial response and stable disease for at least 24 weeks

  • chemo-free interval [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    chemo-free interval is defined as time from last day of chemotherapy in the metastatic setting until first day of next chemotherapy or in patients who have not received chemotherapy in the metastatic setting: the first diagnosis of metastases until start of 1st-line chemotherapy in the metastatic setting.

  • safety by toxicity [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
    Safety by toxicity grades is defined by the NCI-CTCAE version 4.03

  • compliance [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    Compliance will be assessed by the number and reasons of patients whose treatment had to be reduced, delayed or permanently stopped

  • biological marker [ Time Frame: starting in 3 years, biomaterial will be stored, later research possible ] [ Designated as safety issue: No ]
    Bone marker estimation in blood and/or urine


Other Outcome Measures:
  • translational research: search for markers for prediction [ Time Frame: starting in 3 years, biomaterial will be stored, later research possible ] [ Designated as safety issue: No ]
    PI3K/mTor and other related markers in tissue collected directly before study entry


Enrollment: 3
Study Start Date: July 2013
Estimated Study Completion Date: November 2014
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Everolimus
Everolimus is given beyond progress
Drug: Everolimus
Everolimus is given beyond progress (comparison with placebo)
Other Name: Everolimus, Afinitor, RAD-001
Placebo Comparator: Everolimus-placebo
Everolimus-placebo is given beyond progress with Everolimus as a comparator

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 1. Written informed consent prior to beginning specific protocol procedures, including expected cooperation of the patients for the treatment and follow-up, must be obtained and documented according to the local regulatory requirements.

    2. Complete baseline documentation must be submitted via the web-based data collection system MedCODES® to the GBG Forschungs GmbH.

    3. Histological confirmed hormone receptor positive (HR+); HER2-negative carcinoma of the breast. Every effort should be made to make paraffin embedded tissue or slides from the original tumor and/or from metastatic tissue available for confirmation of diagnosis and additional translational research.

    4. Postmenopausal women 5. HER2-negative, hormone-receptor-positive, locally advanced or metastatic stage of disease not amenable to curative treatment by surgery or radiotherapy alone.

    6. No indication for chemotherapy 7. Patients must have either measurable or non-measurable target lesions according to RECIST criteria. Complete staging work-up within 4 weeks prior to registration including chest and abdominal CT scan or MRI (exceptionally chest X-ray and abdominal ultrasound), and bone scan. Further tests have to be performed according to RECIST or as clinically indicated.

    8. Disease progression during or after previous exemestane and everolimus treatment as follows (everolimus has to be given previously for at least 12 weeks, treatment-free interval of everolimus for a maximum of 6 weeks until randomization) 9. The following previous systemic treatments are eligible:

  • Previous participation in other everolimus-containing trials, e.g. the GeparQuinto, BOLERO, 4EVER study is allowed.
  • (Neo)Adjuvant and up to 1 chemotherapy regimen for metastatic breast cancer
  • Maximum of two lines as palliative endocrine monotherapy
  • Treatment with bisphosphonates and/or denosumab (adjuvant and/or palliative) 10. At least 4 weeks since radiotherapy, with full recovery. The measurable disease must be completely outside the radiation field or there must be pathologic proof of newly progressive disease.

    11. Age ≥ 18 years 12. ECOG performance status 0-2 13. Laboratory requirements:

    • Absolute neutrophil count at least 1500 cells/microliter,
    • hemoglobin ≥9.0 g/dL (hemoglobin <9.0 g/dL is acceptable if it is corrected by growth factor or transfusion)
    • platelet count at least 100,000 cells/microliter.
    • bilirubin at least 1.5x the upper limit of normal for the institution (ULN);
    • elevation of transaminases and alkaline phosphatase <3x ULN or <5x ULN for patients with liver metastases.
    • BUN (blood urea nitrogen) ≤ULN
    • Fasting plasma glucose (FPG) ≤160 mg/dL or ≤8.9 mmol/L
    • Fasting serum cholesterol ≤ 300mg/dl or 7.75mmol/L (LDL cholesterol <190mg/dl) and fasting triglyceride ≤2.5xULN (<300mg/dl). In case one or both of these thresholds are exceeded the patient can only be included after initiation of a statin therapy and when above mentioned values have been achieved.

INR ≤2.0 Creatinine not more than 2.0 x ULN or creatinine-clearance >40 ml/min (according to Cockcroft-Gault).

Urine dipstick for proteinuria <2+. Patients discovered to have ≥2+ proteinuria on dipstick urinalysis should undergo a 24 hour urine collection and must demonstrate ≤1 g of protein in 24 hours 14. Patients must be available and compliant for treatment and follow-up. Patients registered on this trial must be treated and followed up at the participating or a cooperating center.

Exclusion Criteria:

  • 1. No documented progression on everolimus plus exemestane 2. Known hypersensitivity reaction to the compounds or incorporated substances 3. Treatment with medroxyprogesteronacetate, megestrolacetate, or high-dose estradiol within 12 weeks of study entry.

    4. Concurrent immunotherapy or hormonal therapy (contraceptive and/or replacement therapy). Bisphosphonates or denosumab may be continued 5. Life expectancy of less than 3 months. 6. Parenchymal brain metastases, unless adequately controlled by surgery and/or radiotherapy.

    7. Any ongoing toxicity from prior anti-cancer therapy that is grade 3-4 and/or that is progressing in severity, except alopecia or anemia controlled by growth factors.

    8. Any previous adverse event grade 3-4 or serious adverse event during treatment with exemestane and everolimus which led to treatment discontinuation 9. Known or suspected congestive heart failure (>NYHA I) and/or coronary heart disease, angina pectoris requiring anti-anginal medication, previous history of myocardial infarction ≤ 6months, evidence of transmural infarction on ECG, un- or poorly controlled arterial hypertension (i.e. BP >150/100 mmHg under treatment with two antihypertensive drugs), rhythm abnormalities requiring permanent treatment, clinically significant valvular heart disease 10. Currently active infection 11. History of other malignancies within the last 5 years which significantly affect the diagnosis, assessment or prognosis of metastatic breast cancer.

    12. Malabsorption syndrome or insufficient gastrointestinal function, preexisting diagnosis of ulcerative colitis 13. Concurrent treatment with other experimental drugs; participation in another clinical trial with any investigational not marketed drug within 30 days prior to study entry.

    14. Insufficiently controlled diabetes 15. known HIV infection or chronic hepatitis B or C 16. seriously impaired liver function (Child-Pugh, class C) 17. Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures (including severe pulmonary conditions, AIDS and serious active infection and diabetes mellitus).

    18. Male patients 19. Known HIV infection or chronic or history of hepatitis B or C 20. Seriously impaired liver function (Child-Pugh, class C)

  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01773460

Locations
Germany
Klinikum Offenbach
Offenbach, Hessen, Germany, 63069
Sponsors and Collaborators
German Breast Group
Novartis
Investigators
Study Chair: Sibylle Loibl, Prof. Krankenhaus Offenbach
  More Information

No publications provided

Responsible Party: German Breast Group
ClinicalTrials.gov Identifier: NCT01773460     History of Changes
Other Study ID Numbers: GBG 76
Study First Received: January 15, 2013
Last Updated: July 25, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by German Breast Group:
everolimus progress exemestane
treated with exemestane and everolimus
progress under this treatment

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Exemestane
Sirolimus
Everolimus
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Aromatase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents

ClinicalTrials.gov processed this record on August 26, 2014