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BI 836845 in Estrogen Receptor Positive Metastatic Breast Cancer

Sponsor
Boehringer Ingelheim (Industry)
Overall Status
Completed
CT.gov ID
NCT02123823
Collaborator
(none)
164
Enrollment
38
Locations
3
Arms
91
Actual Duration (Months)
4.3
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Phase Ib / II study to determine the Maximum Tolerated Dose and Recommended Phase II Dose, and to evaluate the safety and antitumour activity, of BI 836845 and everolimus in combination with exemestane in women with HR+/HER2- advanced breast cancer

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
164 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase Ib/II Randomized Study of BI 836845 in Combination With Exemestane and Everolimus Versus Exemestane and Everolimus Alone in Women With Locally Advanced or Metastatic Breast Cancer
Actual Study Start Date :
May 15, 2014
Actual Primary Completion Date :
Nov 25, 2016
Actual Study Completion Date :
Dec 14, 2021

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Everolimus 10mg + Exemestane 25mg

Phase II - Daily everolimus oral administration 10mg + daily exemestane 25 mg orally

Drug: Everolimus
10mg dose

Drug: Exemestane
Fixed dose at 25mg
Experimental: BI836845 + Everolimus + Exemestane

Phase II - BI 836845 recommended dose will be administered intravenously once every week, in addition to daily everolimus (oral administration at recommended dose) + daily exemestane 25 mg orally

Drug: Everolimus
at recommended dose as per Phase I data

Drug: BI 836845
Human monoclonal antibody at recommended dose as per Phase I data
Other Names:
  • xentuzumab

    • Drug: Exemestane
    Fixed dose at 25mg
    Experimental: PhI - BI836845 + Everolimus + Exemestane

    Phase I - Dose escalation (24-48 patients) BI 836845 low or high dose, Everolimus 5mg, 7,5mg or 10 mg and Exemestane 25mg

    Drug: Everolimus
    Dose escalation (24-48 patients) in Phase I. 3 dose levels depending on the dose cohort explored: 5mg, 7,5mg and 10mg

    Drug: Exemestane
    Fixed dose at 25mg

    Drug: BI 836845
    Human monoclonal antibody. Dose escalation (24-48 patients) in Phase I. 2 dose levels (high or low) depending on the dose cohort explored
    Other Names:
  • xentuzumab

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Progression-free survival (PFS) [up to 11 months]

    2. Occurrence of Dose Limiting Toxicity (DLT) - phase I part [up to 28 days]

    3. Maximum Tolerated Dose (MTD) - phase I part [up to 15 months]

    Secondary Outcome Measures

    1. Objective response (OR), defined as complete response (CR) or partial response (PR) (CR + PR) [up to 11 months]

    2. Time to progression (TTP), defined as the duration of time from the date of randomization until the date of the first objective tumor progression [up to 11 months]

    3. Disease control (DC), defined as best overall response of complete response (CR) or partial response (PR), or stable disease (SD) >=24 weeks, or Non-CR/Non-PD for >=24 weeks (CR + PR + SD24w + Non-CR/Non-PD24w) [up to 11 months]

    4. Time to objective response, defined as the time from randomisation until first documented CR or PR [up to 11 months]

    5. Duration of objective response, defined as the time from first documented CR or PR until the earliest of disease progression or death among patients with OR [up to 11 months]

    6. Duration of disease control, defined as the time from randomisation until the earliest of disease progression or death, among patients with disease control [up to 11 months]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 99 Years
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    No
    Inclusion criteria:

    • Histologically-confirmed locally advanced (aBC) or metastatic breast cancer (mBC) not deemed amenable to curative surgery or curative radiation therapy

    • Tumors are positive for estrogen-receptor (ER) and/or progesterone receptor (PgR).

    • Tumors must be negative for HER2 per local lab testing.

    • Must have adequate archival tumor tissue from surgery or biopsy.

    • Postmenopausal female patients aged >=18 years old.

    • Objective evidence of recurrence or progressive disease on or after the last line of systemic therapy for breast cancer prior to study entry

    • The patient is disease refractory to non-steroidal aromatase inhibitor (letrozole and/or anastrozole)

    • Patients must have: a) Measurable lesion according to RECIST version 1.1 (R09-0262) or

    1. Bone lesions: lytic or mixed (lytic + sclerotic) in the absence of measurable lesion as defined above

    • Eastern Cooperative Oncology Group performance score <= 2.

    • Life expectancy of >= 6 months in the opinion of the investigator

    • Fasting plasma glucose < 8.9 mmol/L (< 160 mg/dL) and HbA1c < 8.0%

    • Adequate organ function

    • Recovered from any previous therapy related toxicity to <= Grade 1 at study entry (except for stable sensory neuropathy <=Grade 2 and alopecia)

    • Written informed consent that is consistent with ICH-GCP guidelines and local regulations

    Inclusion criteria for the biopsy substudy are identical to the main study of the phase II part except for the following two inclusion criteria:

    • Fresh tumor biopsy should be taken when deemed safe and feasible by the investigator and upon informed consent by the patient. Bone lesion is not recommended for biopsy

    • Patients eligible to undergo tumor biopsy should have normal coagulation parameters (INR and PTT within normal range)

    Exclusion criteria:

    • Previous treatment with agents targeting on IGF pathway, phosphoinositide 3-kinase (PI3K) signaling pathway, protein kinase B (AKT), or mammalian target of rapamycin (mTOR) pathways

    • Prior treatment with exemestane (except adjuvant exemestane stopped >12 months prior to start of study treatment as long as the patient did not recur during or within 12 months after the end of adjuvant exemestane)

    • Known hypersensitivity to monoclonal antibody, mTOR inhibitors (e.g. sirolimus), or to the excipients of any study drugs

    • Ovarian suppression by ovarian radiation or treatment with a luteinizing hormone-releasing hormone (LH-RH) agonist

    • Less than one week after receiving immunization with attenuated live vaccines prior to study treatment

    • Radiotherapy within 4 weeks prior to the start of the study treatment, except in case of localized radiotherapy for analgesic purpose or for lytic lesions at risk of fracture which can then be completed within two weeks prior to study treatment

    • Chemotherapy, biological therapy (other than bevacizumab), immunotherapy or investigational agents within 5 half-life of the drug or within two weeks prior to the start of study treatment, whichever is longer; bevacizumab treatment within 4 weeks prior to start of study treatment (this criterion concerns anti-cancer therapy only)

    • Hormonal treatment for breast cancer within 2 weeks prior to start of study treatment

    • Major surgery in the judgement of the investigator within 4 weeks before starting study treatment or scheduled for surgery during the projected course of the study

    • Patients receiving concomitant immunosuppressive agents or chronic corticosteroids use except Topical applications, inhaled sprays, eye drops or local injections or Patients on stable low dose of corticosteroids for at least two weeks before study entry

    • Chronic hepatitis B infection, chronic hepatitis C infection and/or known HIV carrier

    • QTcF prolongation > 470 ms or QT prolongation deemed clinically relevant by the investigator

    • Disease that is considered by the investigator to be rapidly progressing or life threatening such as extensive symptomatic visceral disease including hepatic involvement and pulmonary lymphangitic spread of tumor

    • History or current presence of brain or other CNS metastases

    • Bilateral diffuse lymphangitic carcinomatosis (in lung)

    • Hypokalemia of Grade >1

    • History of another primary malignancy within 5 years, with the exception of adequately treated in-situ carcinoma of the cervix, uteri, basal or squamous cell carcinoma or non-melanomatous skin cancer

    • Family history of long QT syndrome

    • Any concomitant serious illness or organ system dysfunction which in the opinion of the investigator would either compromise patient safety or interfere with the evaluation of the safety and anti-tumor activity of the test drug(s)

    • Patients being treated with drugs recognized being strong or moderate CYP3A4 and/or PgP inhibitors and/or strong CYP3A4 inducers within 2 weeks prior to study entry

    • Patients received more than two lines of chemotherapy for locally advanced or metastatic breast cancer (For the Phase II: more than one line)

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 LKH-Univ. Hospital Graz Graz Austria 8036
    2 Wilhelminenspital Wien Austria 1160
    3 Brussels - UNIV UZ Brussel Brussel Belgium 1090
    4 Brussels - UNIV Saint-Luc Bruxelles Belgium 1200
    5 Charleroi - HOSP Grand Hôpital de Charleroi Charleroi Belgium 6000
    6 Edegem - UNIV UZ Antwerpen Edegem Belgium 2650
    7 UZ Leuven Leuven Belgium 3000
    8 Centre Hospitalier Universitaire de Liège Liège Belgium 4000
    9 Liège - HOSP St-Joseph Liège Belgium 4000
    10 CHU UCL Namur - Site De Sainte-Elisabeth Namur Belgium 5000
    11 HOP Jean Minjoz Besançon France 25030
    12 INS Paoli-Calmettes Marseille France 13009
    13 CTR Catherine de Sienne Nantes France 44202
    14 HOP Européen G. Pompidou Paris France 75015
    15 INS Curie Paris France 75248
    16 Ctr Cario Plerin Sur Mer France 22190
    17 St Vincent's University Hospital Dublin 4 Ireland D04 T6F4
    18 National Cancer Center Goyang Korea, Republic of 10408
    19 Seoul National University Hospital Seoul Korea, Republic of 110-744
    20 Asan Medical Center Seoul Korea, Republic of 138-736
    21 Maastricht University Maastricht Netherlands 6229 HX
    22 Hospital Vall d'Hebron Barcelona Spain 08035
    23 Hospital Clínic de Barcelona Barcelona Spain 08036
    24 Hospital Arnau de Vilanova Lleida Spain 25198
    25 MD Anderson Cancer Center Madrid Madrid Spain 28033
    26 Hospital Ramón y Cajal Madrid Spain 28034
    27 Hospital Clínico San Carlos Madrid Spain 28040
    28 Hospital Universitario 12 de Octubre Madrid Spain 28041
    29 Hospital Virgen del Rocío Sevilla Spain 41013
    30 Hospital Clínico de Valencia Valencia Spain 46010
    31 Centrummottagningen Stockholm Sweden 171 76
    32 Kaohsiung Medical University Chung-Ho Memorial Hospital Kaohsiung Taiwan 8807
    33 Taichung Veterans General Hospital Taichung Taiwan 40705
    34 National Taiwan University Hospital Taipei Taiwan 10002
    35 Taipei Veterans General Hospital Taipei Taiwan 112
    36 Ninewells Hospital & Medical School Dundee United Kingdom DD1 9SY
    37 St Bartholomew's Hospital London United Kingdom EC1M 6BQ
    38 Freeman Hospital Newcastle Upon Tyne United Kingdom NE7 7DN

    Sponsors and Collaborators

    • Boehringer Ingelheim

    Investigators

    • Study Chair: Boehringer Ingelheim, Boehringer Ingelheim

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Boehringer Ingelheim
    ClinicalTrials.gov Identifier:
    NCT02123823
    Other Study ID Numbers:
    • 1280.4
    • 2013-001110-15
    • 1280-0004
    First Posted:
    Apr 28, 2014
    Last Update Posted:
    Feb 3, 2022
    Last Verified:
    Feb 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Additional relevant MeSH terms:
    Everolimus
    Exemestane

    Study Results

    No Results Posted as of Feb 3, 2022