BI 836845 in Estrogen Receptor Positive Metastatic Breast Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2015 by Boehringer Ingelheim
Information provided by (Responsible Party):
Boehringer Ingelheim Identifier:
First received: April 22, 2014
Last updated: November 16, 2015
Last verified: November 2015
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 Intervention Phase
Drug: Everolimus
Drug: Exemestane
Drug: BI 836845
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:

Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Progression-free survival (PFS) [ Time Frame: up to 11 months ] [ Designated as safety issue: No ]
  • occurrence of Dose Limiting Toxicity (DLT) - phase I part [ Time Frame: up to 28 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Objective response (OR), defined as complete response (CR) or partial response (PR) (CR + PR) [ Time Frame: up to 11 months ] [ Designated as safety issue: No ]
  • Time to objective response [ Time Frame: up to 11 months ] [ Designated as safety issue: No ]
  • Duration of objective response [ Time Frame: up to 11 months ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Duration of disease control [ Time Frame: up to 11 months ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 198
Study Start Date: May 2014
Estimated Study Completion Date: January 2018
Estimated Primary Completion Date: August 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
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


Ages Eligible for Study:   18 Years to 99 Years
Genders 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 Measurable lesion according to RECIST version 1.1 or Bone lesions only: 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 of brain or other CNS metastases
  • Bilateral diffuse lymphangitic carcinomatosis
  • 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
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 identifier: NCT02123823

Contact: Boehringer Ingelheim Call Center 1-800-243-0127

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Sponsors and Collaborators
Boehringer Ingelheim
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

No publications provided

Responsible Party: Boehringer Ingelheim Identifier: NCT02123823     History of Changes
Other Study ID Numbers: 1280.4, 2013-001110-15
Study First Received: April 22, 2014
Last Updated: November 16, 2015
Health Authority: Belgium: Federal Agency for Medicinal and Health Products
France: Agence Nationale de Sécurité du Médicament et des produits de santé
Ireland: Health Products Regulatory Authority (HPRA)
Korea: Ministry of Food and Drug Safety
Netherlands: Central Committee Research Involving Human Subjects
Spain: Spanish Agency of Medicines
Sweden: Medical Products Agency
Taiwan : Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Austria: Austrian Medicines and Medical Devices Agency

Additional relevant MeSH terms:
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents
Aromatase Inhibitors
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses processed this record on November 27, 2015