BI 836845 in Estrogen Receptor Positive Metastatic Breast Cancer

Neoplasms Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02123823
• Other study ID #: 1280.4
• Secondary ID: 2013-001110-1512
• Status: Completed
• Phase: Phase 1
• Start date: May 15, 2014
• Est. completion date: December 14, 2021

Study information

• Verified date: February 2022
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 164
• Est. completion date: December 14, 2021
• Est. primary completion date: November 25, 2016
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 99 Years

Eligibility

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)

Related Conditions & MeSH terms

• Neoplasms

Intervention

Drug:
• Everolimus
10mg dose
• Everolimus
at recommended dose as per Phase I data
• Everolimus
Dose escalation (24-48 patients) in Phase I. 3 dose levels depending on the dose cohort explored: 5mg, 7,5mg and 10mg
• Exemestane
Fixed dose at 25mg
• BI 836845
Human monoclonal antibody at recommended dose as per Phase I data
• 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
• Exemestane
Fixed dose at 25mg
• Exemestane
Fixed dose at 25mg

Locations

Country	Name	City	State
Austria	LKH-Univ. Hospital Graz	Graz
Austria	Wilhelminenspital	Wien
Belgium	Brussels - UNIV UZ Brussel	Brussel
Belgium	Brussels - UNIV Saint-Luc	Bruxelles
Belgium	Charleroi - HOSP Grand Hôpital de Charleroi	Charleroi
Belgium	Edegem - UNIV UZ Antwerpen	Edegem
Belgium	UZ Leuven	Leuven
Belgium	Centre Hospitalier Universitaire de Liège	Liège
Belgium	Liège - HOSP St-Joseph	Liège
Belgium	CHU UCL Namur - Site De Sainte-Elisabeth	Namur
France	HOP Jean Minjoz	Besançon
France	INS Paoli-Calmettes	Marseille
France	CTR Catherine de Sienne	Nantes
France	HOP Européen G. Pompidou	Paris
France	INS Curie	Paris
France	Ctr Cario	Plerin Sur Mer
Ireland	St Vincent's University Hospital	Dublin 4
Korea, Republic of	National Cancer Center	Goyang
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Netherlands	Maastricht University	Maastricht
Spain	Hospital Clínic de Barcelona	Barcelona
Spain	Hospital Vall d'Hebron	Barcelona
Spain	Hospital Arnau de Vilanova	Lleida
Spain	Hospital Clínico San Carlos	Madrid
Spain	Hospital Ramón y Cajal	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	MD Anderson Cancer Center Madrid	Madrid
Spain	Hospital Virgen del Rocío	Sevilla
Spain	Hospital Clínico de Valencia	Valencia
Sweden	Centrummottagningen	Stockholm
Taiwan	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung
Taiwan	Taichung Veterans General Hospital	Taichung
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei
United Kingdom	Ninewells Hospital & Medical School	Dundee
United Kingdom	St Bartholomew's Hospital	London
United Kingdom	Freeman Hospital	Newcastle Upon Tyne

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

Austria,  Belgium,  France,  Ireland,  Korea, Republic of,  Netherlands,  Spain,  Sweden,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival (PFS)		up to 11 months
Primary	Occurrence of Dose Limiting Toxicity (DLT) - phase I part		up to 28 days
Primary	Maximum Tolerated Dose (MTD) - phase I part		up to 15 months
Secondary	Objective response (OR), defined as complete response (CR) or partial response (PR) (CR + PR)		up to 11 months
Secondary	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
Secondary	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
Secondary	Time to objective response, defined as the time from randomisation until first documented CR or PR		up to 11 months
Secondary	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
Secondary	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

External Links

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