Everolimus Beyond Progress for Patients Who Had Progress Under Everolimus and Exemestane

NCT01773460 | Terminated Phase 3 DMC

• 1 other identifier: GBG 76
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Metastatic Breast Cancer

Keywords

everolimus progress exemestane; treated with exemestane and everolimus; progress under this treatment

Outcome Measures

Primary Outcomes (1)

• progression free survival

  comparison of progression free survival between the two arms: with Everolimus or with Everolimus-placebo

  3 years

Secondary Outcomes (6)

• overall survival

  3 years

• clinical benefit Rate(CBR)

  3 years

• chemo-free interval

  3 years

• safety by toxicity

  3 years

• compliance

  3 years

Other Outcomes (1)

• translational research: search for markers for prediction

  starting in 3 years, biomaterial will be stored, later research possible

Study Arms (2)

Everolimus

EXPERIMENTAL

Everolimus is given beyond progress

Drug: Everolimus

Everolimus-placebo

PLACEBO COMPARATOR

Everolimus-placebo is given beyond progress

Drug: Everolimus-placebo

Interventions

Everolimus DRUG

Everolimus is given beyond progress (comparison with placebo)

Also known as: Everolimus, Afinitor, RAD-001

Everolimus

Everolimus-placebo DRUG

Everolimus-placebo

Also known as: placebo

Everolimus-placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• GBG Forschungs GmbH: lead
• Novartis: collaborator

Study Sites (1)

Klinikum Offenbach

Offenbach, Hesse, 63069, Germany

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Everolimus

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Sibylle Loibl, Prof.

  Krankenhaus Offenbach

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 15, 2013
• First Posted: January 23, 2013
• Study Start: July 1, 2013
• Primary Completion: July 1, 2014
• Study Completion: July 1, 2014
• Last Updated: February 10, 2016

Record last verified: 2016-02

Locations

DE (1)