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BI 836845 in Estrogen Receptor Positive Metastatic Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02123823
Recruitment Status : Active, not recruiting
First Posted : April 28, 2014
Last Update Posted : May 15, 2019
Information provided by (Responsible Party):
Boehringer Ingelheim

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
Neoplasms Drug: Everolimus Drug: Exemestane Drug: BI 836845 Phase 1

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Study Type : Interventional  (Clinical Trial)
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 : November 25, 2016
Estimated Study Completion Date : November 12, 2019

Resource links provided by the National Library of Medicine

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 Name: 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 Name: xentuzumab

Primary Outcome Measures :
  1. Progression-free survival (PFS) [ Time Frame: up to 11 months ]
  2. Occurrence of Dose Limiting Toxicity (DLT) - phase I part [ Time Frame: up to 28 days ]
  3. Maximum Tolerated Dose (MTD) - phase I part [ Time Frame: up to 15 months ]

Secondary Outcome Measures :
  1. Objective response (OR), defined as complete response (CR) or partial response (PR) (CR + PR) [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: up to 11 months ]
  4. Time to objective response, defined as the time from randomisation until first documented CR or PR [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: up to 11 months ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
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 b) 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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02123823

  Hide Study Locations
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LKH-Univ. Hospital Graz
Graz, Austria, 8036
Wien, Austria, 1160
Brussels - UNIV UZ Brussel
Brussel, Belgium, 1090
Brussels - UNIV Saint-Luc
Bruxelles, Belgium, 1200
Charleroi - HOSP Grand Hôpital de Charleroi
Charleroi, Belgium, 6000
Edegem - UNIV UZ Antwerpen
Edegem, Belgium, 2650
UZ Leuven
Leuven, Belgium, 3000
Centre Hospitalier Universitaire de Liège
Liège, Belgium, 4000
Liège - HOSP St-Joseph
Liège, Belgium, 4000
Namur - HOSP Ste-Elisabeth
Namur, Belgium, 5000
HOP Jean Minjoz
Besançon, France, 25030
INS Paoli-Calmettes
Marseille, France, 13009
CTR Catherine de Sienne
Nantes, France, 44202
HOP Européen G. Pompidou
Paris, France, 75015
INS Curie
Paris, France, 75248
Ctr Cario
Plerin Sur Mer, France, 22190
St Vincent's University Hospital
Dublin 4, Ireland, D04 T6F4
Korea, Republic of
National Cancer Center
Goyang, Korea, Republic of, 410-769
Seoul National University Hospital
Seoul, Korea, Republic of, 110-744
Asan Medical Center
Seoul, Korea, Republic of, 138-736
Maastricht Universitair Medisch Centrum
Maastricht, Netherlands, 6229 HX
Hospital Vall d'Hebron
Barcelona, Spain, 08035
Hospital Clínic de Barcelona
Barcelona, Spain, 08036
Hospital Arnau de Vilanova
Lleida, Spain, 25198
MD Anderson Cancer Center Madrid
Madrid, Spain, 28033
Hospital Ramón y Cajal
Madrid, Spain, 28034
Hospital Clínico San Carlos
Madrid, Spain, 28040
Hospital Universitario 12 de Octubre
Madrid, Spain, 28041
Hospital Virgen del Rocío
Sevilla, Spain, 41013
Hospital Clínico de Valencia
Valencia, Spain, 46010
Karolinska Univ. sjukhuset
Stockholm, Sweden, 171 76
Kaohsiung Medical University Chung-Ho Memorial Hospital
Kaohsiung, Taiwan, 8807
Taichung Veterans General Hospital
Taichung, Taiwan, 40705
National Taiwan University Hospital
Taipei, Taiwan, 10002
Taipe Veterans General Hospital
Taipei, Taiwan, 112
United Kingdom
Ninewells Hospital & Medical School
Dundee, United Kingdom, DD1 9SY
St Bartholomew's Hospital
London, United Kingdom, EC1M 6BQ
Freeman Hospital
Newcastle Upon Tyne, United Kingdom, NE7 7DN
Sponsors and Collaborators
Boehringer Ingelheim
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Study Chair: Boehringer Ingelheim Boehringer Ingelheim

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Responsible Party: Boehringer Ingelheim Identifier: NCT02123823     History of Changes
Other Study ID Numbers: 1280.4
2013-001110-15 ( EudraCT Number )
First Posted: April 28, 2014    Key Record Dates
Last Update Posted: May 15, 2019
Last Verified: May 2019

Additional relevant MeSH terms:
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Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists