Description:
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
Title
- Brief Title: BI 836845 in Estrogen Receptor Positive Metastatic Breast Cancer
- 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 IDs
- ORG STUDY ID:
1280.4
- SECONDARY ID:
2013-001110-15
- SECONDARY ID:
1280-0004
- NCT ID:
NCT02123823
Conditions
Interventions
Drug | Synonyms | Arms |
---|
Everolimus | | Everolimus 10mg + Exemestane 25mg |
Everolimus | | BI836845 + Everolimus + Exemestane |
Everolimus | | PhI - BI836845 + Everolimus + Exemestane |
Exemestane | | PhI - BI836845 + Everolimus + Exemestane |
BI 836845 | xentuzumab | BI836845 + Everolimus + Exemestane |
BI 836845 | xentuzumab | PhI - BI836845 + Everolimus + Exemestane |
Exemestane | | BI836845 + Everolimus + Exemestane |
Exemestane | | Everolimus 10mg + Exemestane 25mg |
Purpose
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
Trial Arms
Name | Type | Description | Interventions |
---|
Everolimus 10mg + Exemestane 25mg | Active Comparator | Phase II - Daily everolimus oral administration 10mg + daily exemestane 25 mg orally | |
BI836845 + Everolimus + Exemestane | Experimental | 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 | - Everolimus
- BI 836845
- Exemestane
|
PhI - BI836845 + Everolimus + Exemestane | Experimental | Phase I - Dose escalation (24-48 patients) BI 836845 low or high dose, Everolimus 5mg, 7,5mg or 10 mg and Exemestane 25mg | - Everolimus
- Exemestane
- BI 836845
|
Eligibility Criteria
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)
Maximum Eligible Age: | 99 Years |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | Female |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Progression-free survival (PFS) |
Time Frame: | up to 11 months |
Safety Issue: | |
Description: | |
Secondary Outcome Measures
Measure: | Objective response (OR), defined as complete response (CR) or partial response (PR) (CR + PR) |
Time Frame: | up to 11 months |
Safety Issue: | |
Description: | |
Measure: | 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 |
Safety Issue: | |
Description: | |
Measure: | 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 |
Safety Issue: | |
Description: | |
Measure: | Time to objective response, defined as the time from randomisation until first documented CR or PR |
Time Frame: | up to 11 months |
Safety Issue: | |
Description: | |
Measure: | 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 |
Safety Issue: | |
Description: | |
Measure: | 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 |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Active, not recruiting |
Lead Sponsor: | Boehringer Ingelheim |
Last Updated
August 13, 2021