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. |
ClinicalTrials.gov Identifier: NCT02123823 |
Recruitment Status :
Completed
First Posted : April 28, 2014
Last Update Posted : February 3, 2022
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
Condition or disease | Intervention/treatment | Phase |
---|---|---|
Neoplasms | Drug: Everolimus Drug: Exemestane Drug: BI 836845 | Phase 1 |
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 |
Actual Study Completion Date : | December 14, 2021 |

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 |
- Progression-free survival (PFS) [ Time Frame: up to 11 months ]
- Occurrence of Dose Limiting Toxicity (DLT) - phase I part [ Time Frame: up to 28 days ]
- Maximum Tolerated Dose (MTD) - phase I part [ Time Frame: up to 15 months ]
- Objective response (OR), defined as complete response (CR) or partial response (PR) (CR + PR) [ Time Frame: up to 11 months ]
- 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 ]
- 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 ]
- Time to objective response, defined as the time from randomisation until first documented CR or PR [ Time Frame: up to 11 months ]
- 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 ]
- 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 ]

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, Learn About Clinical Studies.
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)

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 ClinicalTrials.gov identifier (NCT number): NCT02123823

Study Chair: | Boehringer Ingelheim | Boehringer Ingelheim |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: | Boehringer Ingelheim |
ClinicalTrials.gov Identifier: | NCT02123823 |
Other Study ID Numbers: |
1280.4 2013-001110-15 ( EudraCT Number ) 1280-0004 ( Other Identifier: Boehringer Ingelheim ) |
First Posted: | April 28, 2014 Key Record Dates |
Last Update Posted: | February 3, 2022 |
Last Verified: | February 2022 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Yes |
Plan Description: | After the study is completed and the primary manuscript is accepted for publishing, researchers can use this following link https://www.mystudywindow.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed "Document Sharing Agreement". Also, Researchers can use the following link https://www.mystudywindow.com/msw/datasharing to find information in order to request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website. The data shared are the raw clinical study data sets. |
Supporting Materials: |
Study Protocol Statistical Analysis Plan (SAP) Clinical Study Report (CSR) |
Time Frame: | After all regulatory activities are completed in the US and EU for the product and indication, and after the primary manuscript has been accepted for publication. |
Access Criteria: | For study documents - upon signing of a 'Document Sharing Agreement'. For study data - 1. after the submission and approval of the research proposal (checks will be performed by both the independent review panel and the sponsor, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a 'Data Sharing Agreement'. |
URL: | https://www.mystudywindow.com/msw/datasharing |
Everolimus Exemestane Antineoplastic Agents Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Aromatase Inhibitors |
Steroid Synthesis Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Estrogen Antagonists Hormone Antagonists Hormones, Hormone Substitutes, and Hormone Antagonists |