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The XENERA™ 1 Study Tests Xentuzumab in Combination With Everolimus and Exemestane in Women With Hormone Receptor Positive and HER2-negative Breast Cancer That Has Spread

NCT03659136

Description:

The main objective of the trial is to assess the efficacy of xentuzumab in combination with everolimus and exemestane over everolimus and exemestane in patients with HR+/ HER2- advanced or metastatic breast cancer and non-visceral disease.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: The XENERA™ 1 Study Tests Xentuzumab in Combination With Everolimus and Exemestane in Women With Hormone Receptor Positive and HER2-negative Breast Cancer That Has Spread
  • Official Title: XENERA™1: A Multi-centre, Double-blind, Placebo-controlled, Randomised Phase II Trial to Compare Efficacy of Xentuzumab in Combination With Everolimus and Exemestane Versus Everolimus and Exemestane in Women With HR+ / HER2- Metastatic Breast Cancer and Non-visceral Disease

Clinical Trial IDs

  • ORG STUDY ID: 1280-0022
  • SECONDARY ID: 2017-003131-11
  • NCT ID: NCT03659136

Conditions

  • Breast Neoplasms

Interventions

DrugSynonymsArms
XentuzumabXentuzumab/everolimus/exemestane
PlaceboPlacebo/everolimus/exemestane
EverolimusPlacebo/everolimus/exemestane
ExemestanePlacebo/everolimus/exemestane

Purpose

The main objective of the trial is to assess the efficacy of xentuzumab in combination with everolimus and exemestane over everolimus and exemestane in patients with HR+/ HER2- advanced or metastatic breast cancer and non-visceral disease.

Trial Arms

NameTypeDescriptionInterventions
Xentuzumab/everolimus/exemestaneExperimental
  • Xentuzumab
  • Everolimus
  • Exemestane
Placebo/everolimus/exemestanePlacebo Comparator
  • Placebo
  • Everolimus
  • Exemestane

Eligibility Criteria

        Inclusion Criteria:

          -  Documented histologically confirmed breast cancer with ERand/ or PgR-positive and
             HER2-negative status

          -  Locally advanced or metastatic breast cancer not deemed amenable to curative surgery
             or curative radiation therapy

          -  Archival tumour sample available at the time of informed consent and provided to the
             central laboratory around the time of randomisation. Patients must provide a
             formalin-fixed paraffin embedded (FFPE) tissue biopsy sample preferably taken at the
             time of presentation with recurrent or metastatic disease (provision of a biopsy
             sample taken from the bone is not acceptable).

          -  Patients must satisfy the following criteria for prior therapy:

               -  Disease progression during treatment or within 12 months of completion of
                  endocrine adjuvant therapy or

               -  Disease progression while on or within 1 month after the end of prior endocrine
                  therapy for advanced/metastatic breast cancer (Note: the endocrine therapy does
                  not have to be the treatment immediately prior to trial entry).

          -  Patients must have

               -  At least one measurable non-visceral lesion according to RECIST version 1.1 in
                  either lymph nodes, soft tissue, skin and/or

               -  At least one measurable non-visceral lesion according to RECIST version 1.1 as
                  lytic or mixed (lytic + blastic) in bone and/or

               -  At least one non-measurable (lytic, mixed lytic + blastic, or blastic) bone
                  lesion according to RECIST version 1.1

          -  Eastern Cooperative Oncology Group (ECOG) performance score 0 or 1.

          -  Fasting glucose <8.9 mmol/L (<160 mg/dL) and HbA1c <8.0%

          -  Adequate organ function

        Exclusion Criteria:

          -  Previous treatment with agents targeting the IGF pathway, AKT, or 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)

          -  Evidence of visceral metastasis/es (i.e. liver, lung, peritoneal, pleural metastases,
             malignant pleural effusions, malignant peritoneal effusions) at screening. NOTE:
             Patients with a past history of visceral metastases are eligible if visceral
             metastases have completely resolved at least 3 months

          -  History or evidence of metastatic disease to the brain

          -  Leptomeningeal carcinomatosis

          -  More than 1 prior line of chemotherapy for HR+ HER2- metastatic breast cancer

          -  Radiotherapy within 4 weeks prior to the start of study treatment

          -  Use of concomitant systemic sex hormone therapy

          -  History or presence of cardiovascular abnormalities

          -  Known pre-existing interstitial lung disease

          -  Further exclusion criteria apply
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression free survival (PFS) as assessed by central review
Time Frame:Up to 24 months
Safety Issue:
Description:Defined as time from randomisation until disease progression according to Response Evaluation Criteria In Solid Tumors (RECIST, version 1.1) or death from any cause, whichever occurs earlier

Secondary Outcome Measures

Measure:Overall survival (OS) defined as the time from randomisation until death from any cause
Time Frame:Up to 3 years
Safety Issue:
Description:Defined as the time from randomisation until death from any cause
Measure:Disease control (DC)
Time Frame:Up to 24 months
Safety Issue:
Description:Defined as a best overall response of complete response (CR), partial response (PR), stable disease (SD) or Non-CR/Non-Progressive Disease (Non- CR/Non-PD). SD and Non-CR/Non PD must have a minimum duration of 24 weeks from randomisation. Best overall response is defined according to RECIST version 1.1 and will consider all tumour assessments from randomisation until the earliest of disease progression, death or last evaluable tumour assessment before start of subsequent anticancer therapy, loss to follow-up or withdrawal of consent
Measure:Duration of DC is defined as the time from randomisation until the earliest of disease progression or death, among patients with DC
Time Frame:Up to 24 months
Safety Issue:
Description:Defined as the time from randomisation until the earliest of disease progression or death, among patients with DC
Measure:Objective response (OR) Defined as a best overall response of complete response (CR) or partial response (PR)
Time Frame:Up to 24 months
Safety Issue:
Description:Defined as a best overall response of CR or PR. Best overall response is defined according to RECIST version 1.1 and will consider all tumour assessments from randomisation until the earliest of disease progression, death or last evaluable tumour assessment before start of subsequent anti-cancer therapy, loss to follow-up or withdrawal of consent
Measure:Time to pain progression or intensification of pain palliation
Time Frame:Up to 24 months
Safety Issue:
Description:Defined as the time from randomisation until the earliest of a clinically significant increase in pain (≥2-point increase from baseline in the Brief Pain Inventory- Short Form [BPI-SF] Item 3) without a decrease in analgesics use, or intensification in pain palliation (≥2-point increase in the 8-point Analgesic Quantification Algorithm [AQA]), or death

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Boehringer Ingelheim

Last Updated

March 24, 2021