Dose EScalation Induction of EvERolimus

NCT02387099 | Completed Phase 2 DMC

• 1 other identifier: GBG 86
• Study Type: interventional
• Target: 156
• Locations: 1 country
• Sites: 14

Brief Summary

The BOLERO-2 study demonstrated a benefit for patients who received everolimus in addition to exemestane in patients who progressed during/after a non-steroidal aromatase inhibitor; Routine use of everolimus shows an high rate of intolerability due to mucositis/stomatitis especially during the first 12 weeks of treatment leading cause for treatment discontinuation not related to tumor progression; GeparQuinto study (setting III: non-responders): everolimus was given as salvage treatment in combination with paclitaxel for patients without response to 4 cycles epirubicin/cyclophosphamide with/without bevacizumab. A dose-escalation schema was successfully used to improve tolerability of everolimus together with the cytotoxic Agent. Everolimus plus exemestane has improved the prognosis of metastatic breast cancer significantly. Desiree-study aims to improve the tolerability, which is necessary in order to achieve an adequate dose intensity for the patients in Routine care.

Conditions

Breast Cancer; Hormone Receptor Positive Tumor

Keywords

Stage IIIB; Stage IV; Recurrent; Metastatic

Outcome Measures

Primary Outcomes (1)

• cumulative rate Mucositis grade 2-4 (WHO's oral toxicity scale (OTS))

  To compare the cumulative rate of mucositis/stomatitis grade 2-4 (WHO's oral toxicity scale (OTS)) at 12 weeks after start of treatment using a conventional and a dose-escalating schema of everolimus in combination with exemestane in patients with metastatic breast cancer and progression or relapse after non-steroidal aromatase-inhibitor treatment. Endpoint measurement: First episode of mucositis WHO's OTS 2-4 any time during a 12 week period after start of everolimus

  week1 to week 12

Secondary Outcomes (10)

• cumulative rate Mucositis grade 2-4 (WHO's oral toxicity scale (OTS))

  week 1 to 24

• cumulative rate Mucositis any grade (WHO's oral toxicity scale (OTS))

  week 1 to 12 and week 1 to 24

• Patients on conventional dose Everolimus 10mg

  week 12 and week 24

• Clinical Benefit Rate (CBR)

  week 24

• Safety other than Mucositis

  week 1 to 24

Other Outcomes (1)

• Biomarker for Breast Cancer

  Baseline and End of Therapy Visit (week 25-28)

Study Arms (2)

Conventional Everolimus dosing according to label

ACTIVE COMPARATOR

everolimus 10 mg/day, week 1-3: 4x2.5 mg/day (blinded); week 4-24: 10mg/day (open according to label) \+ further treatment according to standard of care

Drug: 3 weeks Conventional Everolimus Dosing; Drug: Open Label Phase with conventional 10mg Everolimus Dosing week 4-24; Drug: Standard Care after 24 weeks

3 week Dose Induction of Everolimus

EXPERIMENTAL

an escalating dose of everolimus as follows: week 1: 1x2.5 mg verum + 3x placebo/day; week 2: 2x2.5 mg verum + 2x placebo/day; week 3: 3x2,5 mg verum + 1x placebo/day; week 4-24: 10 mg/day (open according to label) \+ further treatment according to standard of care

Drug: 3 weeks Dose Induction of Everolimus; Drug: Open Label Phase with conventional 10mg Everolimus Dosing week 4-24; Drug: Standard Care after 24 weeks

Interventions

3 weeks Dose Induction of Everolimus DRUG

Comparing a conventional dosing approach starting with 10 mg at first dose versus a dose-escalating schema over 21 days in patients receiving everolimus in combination with exemestane for treatment of metastatic breast cancer. All patients will be treated within the approved indication of everolimus in combination with exemestane. Patients will be randomized in a 1:1 ratio

3 week Dose Induction of Everolimus

3 weeks Conventional Everolimus Dosing DRUG

Comparing a conventional dosing approach starting with 10 mg at first dose versus a dose-escalating schema over 21 days in patients receiving everolimus in combination with exemestane for treatment of metastatic breast cancer. All patients will be treated within the approved indication of everolimus in combination with exemestane. Patients will be randomized in a 1:1 ratio

Conventional Everolimus dosing according to label

Open Label Phase with conventional 10mg Everolimus Dosing week 4-24 DRUG

All patients will receive open label Everolimus with Exemestane for 21 weeks according to label

3 week Dose Induction of Everolimus; Conventional Everolimus dosing according to label

Standard Care after 24 weeks DRUG

It is up to the discretion of the investigator to continue with Everolimus+Exemestane beyond 24 weeks

3 week Dose Induction of Everolimus; Conventional Everolimus dosing according to label

Eligibility Criteria

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

You may qualify if:

• Locally advanced or metastatic stage of disease not amenable to curative treatment by surgery or radiotherapy alone.
• No indication for chemotherapy (e.g. symptomatic visceral metastasis) -Histological confirmed hormone receptor-positive (HR+), HER2- negative carcinoma of the breast.
• Postmenopausal women
• Disease progression following prior therapy with non steroidal aromatase inhibitors (NSAI), defined as:
• Recurrence while on, or following completion of an adjuvant treatment with Letrozole or Anastrozole, or
• Progression while on or following completion of Letrozole or Anastrozole treatment for ABC/MBC. Note: Non-steroidal aromatase inhibitors (i.e. Letrozole or Anastrozole) do not have to be the last treatment prior to enrollment. Other prior anticancer therapy, e.g. Tamoxifen, Fulvestrant, Exemestane, is also allowed. Patients must have recovered to grade 1 or better from any adverse events (except alopecia) related to previous therapy prior to enrollment.
• 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.

You may not qualify if:

• Concurrent immunotherapy or hormonal therapy (contraceptive and/or replacement therapy). Bisphosphonates or denosumab may be continued or started before randomization.
• Life expectancy of less than 3 months.
• 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.
• 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.
• Currently active infection.
• 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.
• 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, known HIV infection or chronic hepatitis B or C and seriously impaired liver function (Child-Pugh, class A, B or C).

Sponsors & Collaborators

• GBG Forschungs GmbH: lead
• Novartis: collaborator

Study Sites (14)

Sana Klinikum Offenbach / German Breast Group

Neu-Isenburg, Hesse, 63263, Germany

Location

TU Dresden

Dresden, Saxony, 01307, Germany

Location

Unknown Facility

Bielefeld, 33604, Germany

Location

Unknown Facility

Cologne, 50931, Germany

Location

University of Erlangen

Erlangen, 91054, Germany

Location

Unknown Facility

Essen, 45136, Germany

Location

Unknown Facility

Goslar, 38642, Germany

Location

Unknown Facility

Hanau, 63450, Germany

Location

Unknown Facility

Karlsruhe, 76135, Germany

Location

Unknown Facility

Kiel, 24105, Germany

Location

Unknown Facility

Mainz, 55131, Germany

Location

Unknown Facility

München, 80638, Germany

Location

Unknown Facility

Rotenburg (Wümme), 27356, Germany

Location

Unknown Facility

Weinheim, 69469, Germany

Location

Related Publications (1)

• Schmidt M, Lubbe K, Decker T, Thill M, Bauer L, Muller V, Link T, Furlanetto J, Reinisch M, Mundhenke C, Hoffmann O, Zahn MO, Muller L, Denkert C, van Mackelenbergh M, Fasching PA, Burchardi N, Nekljudova V, Loibl S. A multicentre, randomised, double-blind, phase II study to evaluate the tolerability of an induction dose escalation of everolimus in patients with metastatic breast cancer (DESIREE). ESMO Open. 2022 Dec;7(6):100601. doi: 10.1016/j.esmoop.2022.100601. Epub 2022 Nov 7.

  PMID: 36356410 DERIVED

Related Links

• Desiree website on German Breast Group home portal

MeSH Terms

Conditions

Breast Neoplasms; Recurrence; Neoplasm Metastasis

Interventions

Congresses as Topic

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplastic Processes

Intervention Hierarchy (Ancestors)

Organizations; Health Care Economics and Organizations

Study Officials

• Sibylle Loibl, Prof., MD

  ASCO, ESGO, ESMO, DKG, DGGG, AGO, DGS, BIG, BCIRG, St. Gallen Faculty Member, SABCS Faculty member

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 5, 2015
• First Posted: March 12, 2015
• Study Start: May 1, 2015
• Primary Completion: May 1, 2021
• Study Completion: July 1, 2021
• Last Updated: February 23, 2022

Record last verified: 2022-02

Locations

DE (14)