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BI 836845 in Estrogen Receptor Positive Metastatic Breast Cancer

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ClinicalTrials.gov Identifier: NCT02123823
Recruitment Status : Active, not recruiting
First Posted : April 28, 2014
Last Update Posted : May 15, 2019
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Tracking Information
First Submitted Date  ICMJE April 22, 2014
First Posted Date  ICMJE April 28, 2014
Last Update Posted Date May 15, 2019
Actual Study Start Date  ICMJE May 15, 2014
Actual Primary Completion Date November 25, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 30, 2016)
  • 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 ]
Original Primary Outcome Measures  ICMJE
 (submitted: April 24, 2014)
  • 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 ]
Change History Complete list of historical versions of study NCT02123823 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 26, 2016)
  • 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: April 24, 2014)
  • Time to progression (TTP), defined as the duration of time from the date of C1V1until the date of the first objective tumor progression [ Time Frame: up to 11 months ]
  • Objective response (OR), defined as complete response (CR) or partial response (PR) (CR + PR) [ Time Frame: up to 11 months ]
  • Time to objective response [ Time Frame: up to 11 months ]
  • Duration of objective response [ Time Frame: up to 11 months ]
  • Clinical benefit (CB), defined as best overall response of complete response (CR) or partial response (PR), or stable disease (SD) >=6 months, or Non-CR/Non-PD for >=6 months (CR + PR + SD6m + Non-CR/Non-PD6m) [ Time Frame: up to 11 months ]
  • Duration of clinical benefit [ Time Frame: up to 11 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE BI 836845 in Estrogen Receptor Positive Metastatic Breast Cancer
Official Title  ICMJE 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
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
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Neoplasms
Intervention  ICMJE
  • Drug: Everolimus
    10mg dose
  • Drug: Everolimus
    at recommended dose as per Phase I data
  • 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 at recommended dose as per Phase I data
    Other Name: xentuzumab
  • 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
Study Arms  ICMJE
  • Active Comparator: Everolimus 10mg + Exemestane 25mg
    Phase II - Daily everolimus oral administration 10mg + daily exemestane 25 mg orally
    Interventions:
    • Drug: Everolimus
    • Drug: Exemestane
  • 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
    Interventions:
    • Drug: Everolimus
    • Drug: BI 836845
    • Drug: Exemestane
  • 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
    Interventions:
    • Drug: Everolimus
    • Drug: Exemestane
    • Drug: BI 836845
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: February 20, 2017)
164
Original Estimated Enrollment  ICMJE
 (submitted: April 24, 2014)
198
Estimated Study Completion Date  ICMJE November 12, 2019
Actual Primary Completion Date November 25, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years to 99 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Austria,   Belgium,   France,   Ireland,   Korea, Republic of,   Netherlands,   Spain,   Sweden,   Taiwan,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02123823
Other Study ID Numbers  ICMJE 1280.4
2013-001110-15 ( EudraCT Number )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Boehringer Ingelheim
Study Sponsor  ICMJE Boehringer Ingelheim
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
PRS Account Boehringer Ingelheim
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP