Klinische Studien

Detect IV

AcronymISRCTNEudraCTClinicaltrials.govDRKS
Detect IV2013-001269-18NCT02035813DRKS00005884

A multicenter single arm phase III study evaluating the efficacy of everolimus in combination with endocrine therapy in patients with HER2-negative, hormone-receptor positive metastatic breast cancer and persisting HER2-negative circulating tumor cells (CTCs).

Status: Active

Purpose / Objectives

Primary Outcome

  • progression free survival

Secondary Outcomes

  • Overall response rate
  • Disease control rate (DCR)
  • Overall survival (OS)
  • Dynamic of CTCs
  • Change in the activation of the PI3K/Akt/mTOR-pathway in CTCs
  • Levels of pS6

Diagnosis

hormonrezeptor pos, HER2- negativ

CTC positive

Patient attributes

Stage

metastatic

Age

18-99

Inclusion criteria

  • Metastatic breast cancer (MBC), which cannot be cured by surgery or radiotherapy. The primary tumor and/or biopsies must have been confirmed as cancer by histopathology
  • HER2 status (as investigated on all primary tumor tissue and/or biopsies from metastatic sites or loco regional recurrences) must be negative. HER2-negativity is defined as (i.e.: immunohistochemistry (IHC) score 0-1+ or 2+ and fluorescent in situ hybridization (FISH) negative or just FISH negative, whichever was performed) in all tissue samples
  • Indication for an endocrine therapy. (Histological confirmation of estrogen receptor positive (ER+) and/or progesterone receptor positive (PgR+) breast cancer)
  • Any endocrine therapy in the history is allowed.
  • Disease progression following prior treatment with endocrine therapy (endocrine therapy does not have to be the last therapy before inclusion in the trial) 6. Evidence of CTCs. At least one CTC has been detected in 7.5 ml patient blood by means of the CellSearch® Circulating Tumor Cell Kit (Veridex LLC, Raritan, USA)
  • HER2 negativity of all detected CTCs. HER2-negativity is defined as staining < HER2 3+
  • Up to two lines of previous cytostatic treatment for MBC.
  • Adequate organ function within 7 days before date of recruitment, evidenced by the following laboratory results: - absolute neutrophil count ≥ 1500/μL, - platelet count ≥ 100000/μL, - hemoglobin ≥ 9 g/dL, - ALT (SGPT)/AST (SGOT) ≤ 3.0 × ULN, - bilirubin ≤ 2.0 × ULN - creatinine ≤ 2.0 × ULN - serum cholesterol ≤ 2.0 × ULN
  • Postmenopausal women. The investigator must confirm postmenopausal status. Postmenopausal status is defined either by - Age ≥ 55 years and one year or more of amenorrhea - Age < 55 years and one year or more of amenorrhea and postmenopausal levels of FSH and LH - Prior hysterectomy and has postmenopausal levels of FSH and LH - Surgical menopause with bilateral oophorectomy
  • Written informed consent in study participation
  • Undergoing a re-biopsy prior if tissue is accessible, which can be safely biopsied, is optional but desirable
  • Tumor evaluation has been performed within 6 weeks before date of recruitment and results are available
  • Patients must have at least one not previously irradiated lesion that can be evaluated according to RECIST version 1.1 (Eisenhauer 2009). Patients with measurable and non-measurable disease are eligible. Presence of clinically and/or radiologically documented disease.
  • Age ≥ 18 years.
  • ECOG Performance Status ≤ 2.

Exclusion criteria

  • Known hypersensitivity to everolimus or other mTOR inhibitors or to any of the other given drugs.
  • Indication for treatment with chemotherapy.
  • Disease or condition, which might restrain the ability to take or resorb oral medication. This includes malabsorption syndrome, requirement for intravenous (IV) alimentation, prior surgical procedures affecting absorption (for example resection of small bowel or stomach), uncontrolled inflammatory GI disease (e.g., Crohn's disease, ulcerative colitis) and any other diseases significantly affecting gastrointestinal function as well as inability to swallow and retain oral medication for any other reason.
  • Treatment with other investigational agents of any type or anticancer therapy during the trial, within 2 weeks prior to the start of treatment.
  • Known HIV infection.
  • Current active hepatitis B or C, known liver dysfunction according to Child Pugh Classification class B and C or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gall-stones, liver metastases or stable chronic non-viral liver disease per investigator assessment).
  • Concurrent disease or condition that might interfere with adequate assessment or evaluation of study data, or any medical disorder that would make the patient's participation unreasonably hazardous.
  • Other malignant diseases within the last 3 years apart from CIN of the uterine cervix and skin basalioma.
  • Dementia, altered mental status, or any psychiatric or social condition which would prohibit the understanding or rendering of informed consent or which might interfere with the patient's adherence to the protocol.
  • Life expectancy < 3 months.

Trial design

  • Phase II
  • Multicenter
  • Prospective
  • Two-arm
  • Open Label

Intervention

Everolimus in combination with standard endocrine therapy

 

IV b:  Eribulin

Documents (password protected)

Responsibilities in overall trial

Universitätsklinikum Ulm AÖR

  • Tel. +49 (0)731-5000

National Coordinating Investigator

Prof. Dr. Tanja Fehm

Study Sites

Studienzentrum Frauenklinik

Status

Active

Principal Investigator

Dr. med. Wolfram Malter

Deputy of Principal Investigator

  • Dr. med. Johannes Holtschmidt

Subinvestigator

  • Dr. med. Maria Nass
  • Angela Ulhaas
  • Dr. med. Johannes Holtschmidt

Contact at Site