DETECT IV - A Study in Patients With HER2-negative Metastatic Breast Cancer and Persisting HER2-negative Circulating Tumor Cells (CTCs).

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2015 by University of Ulm
Sponsor:
Information provided by (Responsible Party):
Prof. W. Janni, University of Ulm
ClinicalTrials.gov Identifier:
NCT02035813
First received: January 12, 2014
Last updated: January 7, 2015
Last verified: January 2015
  Purpose

Several studies have indicated that determining prevalence and number of circulating tumor cells (CTCs) at various time points during treatment may be an effective tool for assessing treatment efficacy in metastatic breast cancer (MBC). However, even if the prognostic value of CTCs in MBC is well understood, the role of both CTC prevalence and CTC phenotype in predicting treatment response needs further investigation. DETECT IV is a prospective, multicenter, open-label, phase II study in patients with HER2-negative metastatic breast cancer and persisting HER2-negative circulating tumor cells (CTCs). Additional research on CTC dynamics and characteristics will provide a better understanding of the prognostic and predictive value of CTCs and is one step into a more personalized therapy for MBC.


Condition Intervention Phase
HER2-negative Und Hormone-receptor Positive Metastatic Breast Cancer
HER2-negative Circulating Tumor Cells
Postmenopausal Female Patients
Drug: Everolimus
Drug: Eribulin
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: DETECT IV - A Prospective, Multicenter, Open-label, Phase II Study in Patients With HER2-negative Metastatic Breast Cancer and Persisting HER2-negative Circulating Tumor Cells (CTCs).

Resource links provided by NLM:


Further study details as provided by University of Ulm:

Primary Outcome Measures:
  • Progression free survival (PFS) [ Time Frame: 8-12 weeks ] [ Designated as safety issue: No ]
    Time interval from randomization until progressive disease (PD) or death from any cause, whichever comes first


Secondary Outcome Measures:
  • Overall response rate [ Time Frame: 8-12 weeks ] [ Designated as safety issue: No ]
    Rate of complete (CR) and partial responses (PR) in patients with whom target lesions were defined

  • Disease control rate (DCR) [ Time Frame: 8-12 weeks ] [ Designated as safety issue: No ]
    rate of patients who were assessed as having a PR or a CR or who had stable disease (SD) for at least 6 months

  • Overall survival (OS) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    Time from randomization until death of any cause

  • Dynamic of CTCs [ Time Frame: 8-12 weeks ] [ Designated as safety issue: No ]
    Descriptive statistics of regular CTC counts

  • For Everolimus cohort only: Levels of pS6 [ Time Frame: 8-12 weeks ] [ Designated as safety issue: No ]
    Descriptive statistics of pS6 levels at baseline, at first radiological tumor assessment after about 12 weeks, and at the time of progression

  • For Everolimus cohort only: Change in the activation of the PI3K/Akt/mTOR-pathway in CTCs [ Time Frame: 8-12 weeks ] [ Designated as safety issue: No ]
    Descriptive statistics of changes in the activation of the PI3K/Akt/mTOR-pathway in CTCs as assessed by longitudinal comparisons (at baseline, after 12 weeks, at time of progression)

  • For Everolimus cohort only: Estrogen-receptor 1 (ESR-1) mutations in CTCs [ Time Frame: 8-12 weeks ] [ Designated as safety issue: No ]
    Estrogen-receptor 1 (ESR-1) mutations in CTCs at baseline, after 12 weeks and at time of progression

  • For Eribulin cohort only: New metastasis-free survival (nMFS) [ Time Frame: 8-12 weeks ] [ Designated as safety issue: No ]
    New metastasis-free survival (nMFS), defined as time from recruitment to death or progression due to appearance of a new metastasis, whichever comes first. If a patient has not had an event, nMFS is censored at the date of last adequate tumor as-sessment


Estimated Enrollment: 520
Study Start Date: January 2014
Estimated Primary Completion Date: December 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Everolimus in combination with standard endocrine therapy
Postmenopausal female patients with hormone-receptor positive, HER2-negative metastatic breast cancer with HER2-negative circulating tumor cells (CTCs) and indication for standard endocrine therapy.
Drug: Everolimus
Everolimus in combination with endocrine therapy
Other Name: Afinitor
Experimental: Eriubulin
Patients with hormone-receptor positive, HER2-negative metastatic breast cancer and indication to chemother-apy or patients with triple-negative metastatic breast cancer, both with HER2-negative circulating tumor cells (CTCs).
Drug: Eribulin
Other Name: Halaven

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

In General for both study cohorts

  1. Metastatic breast cancer, which cannot be cured by surgery or radiotherapy. The primary tumor and/or biopsies must have be confirmed as cancer by histolopathology.
  2. HER2 status (as investigated on all primary tumor tissue and/or biopsies from metastatic sites or loco regional recur-rences) must be negative. HER2-negativity is defined as (i.e.: immunohistochemistry (IHC) score 0-1+ or 2+ and flu-orescent in situ hybridization (FISH) negative or just FISH negative, whichever was performed) in all tissue sam-ples.
  3. Evidence of CTCs. At least one CTC has been detected in 7.5 ml patient blood by means of the CellSearch® Circu-lating Tumor Cell Kit (Veridex LLC, Raritan, USA).
  4. HER2 negativity of all detected CTCs. HER2-negativity is defined as staining < HER2 3+.
  5. 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) ≤ 3.0 × ULN
    • AST (SGOT) ≤ 3.0 × ULN
    • bilirubin ≤ 2.0 × ULN
    • creatinine ≤ 2.0 × ULN.
  6. Written informed consent in study participation.
  7. Undergoing a re-biopsy prior to inclusion if tissue is accessible, which can be safely biopsied, is otional but desira-ble.
  8. Tumor evaluation has been performed within 6 weeks before date of recruitment and results are available.
  9. 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.
  10. Age ≥ 18 years.
  11. ECOG Performance Status ≤ 2.

For Everolimus only:

  • Indication for an endocrine therapy (Histological confirmation of estrogen receptor positive (ER+) and/or progesterone receptor positive (PgR+) breast cancer).
  • Up to two lines of previous cytostatic treatment for MBC.
  • Any endocrine therapy in the history is allowed.
  • Cholesterol ≤ 2.0 × ULN.
  • Disease progression following prior treatment with endocrine therapy (endocrine therapy does not have to be the last therapy before inclusion in the trial).
  • Postmenopausal women. The investigator must confirm postmenopausal status Postmenopausal status is defined either by

    • Age ≥ 55 years and one year or more of amen-orrhea
    • Age < 55 years and one year or more of amen-orrhea and postmenopausal levels of FSH and LH
    • Prior hysterectomy and has postmenopausal levels of FSH and LH
    • Surgical menopause with bilateral oophorecto-my

For Eribulin only:

  • Either hormone-receptor negative MBC or hormone-receptor positive MBC with indication for chemotherapy
  • Up to three previous chemotherapy treatment lines for metastatic disease
  • In case of patients of child bearing potential:

    • Negative pregnancy test (minimum sensitivity 25IU/L or equivalent units of HCG) within 7 days prior to recruitment
    • Contraception by means of a reliable method (i.e. non-hormonal contraception, IUD, a dou-ble barrier method, vasectomy of the sexual partner, complete sexual abstinence). Patient must consent in maintaining such contracep-tion until 3 months after completion of study treatment

Exclusion Criteria:

In General for both study cohorts:

  1. Treatment with other investigational agents of any type or anticancer therapy during the trial, within 2 weeks prior to the start of treatment.
  2. Adverse events due to prior anticancer therapy which are > Grade 1 (NCI CTCAE) and therapeutically relevant at time of treatment start.
  3. Known HIV infection.
  4. Current active hepatitis B or C, cliniclally relevant known liver dysfunction, e.g. according to Child Pugh Classifica-tion 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).
  5. 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.
  6. Other malignant diseases within the last 3 years (apart from carcinoma in situ of the cervix or non-melanoma skin cancer)
  7. 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.
  8. Life expectancy < 3 months.
  9. Male gender.

For Everolimus only:

  • Known hypersensitivity to everolimus or other mTOR inhibitors, e.g. Sirolimus (rapamycin), or any of the other given drugs.
  • Disease or condition, which might restrain the ability to take or resorb oral medication. This includes malabsorption syndrome, requirement for intrave-nous (IV) alimentation, prior surgical procedures af-fecting 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 gas-trointestinal function as well as inability to swallow and retain oral medication for any other reason.

For Eribulin only:

  • History of hypersensitivity reactions attributed to eribulin.
  • Pre-existing neuropathy grade 3 or higher.
  • Severe Congenital long QT syndrome.
  • Pregnancy or nursing.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02035813

Contacts
Contact: Susanne Albrecht, MD studienzentrale.ufk@uniklinik-ulm.de
Contact: Fabienne Schochter, MD studienzentrale.ufk@uniklinik-ulm.de

Locations
Germany
University Hospital Ulm -Department of Gynecology Recruiting
Ulm, Baden-Württemberg, Germany, 89075
Contact: Wolfgang Janni, MD, PhD         
Sponsors and Collaborators
Prof. W. Janni
Investigators
Principal Investigator: Tanja Fehm, MD, PhD University Hospital Düsseldorf -Department of Gynecology
Study Director: Wolfgang Janni, MD, PhD University Hospital Ulm -Department of Gynecology
  More Information

Additional Information:
No publications provided

Responsible Party: Prof. W. Janni, University hospital Ulm - Department of Gynecology, University of Ulm
ClinicalTrials.gov Identifier: NCT02035813     History of Changes
Other Study ID Numbers: D-IV, 2013-001269-18
Study First Received: January 12, 2014
Last Updated: January 7, 2015
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by University of Ulm:
metastatic breast cancer
circulating tumor cells
everolimus
eribulin

Additional relevant MeSH terms:
Breast Neoplasms
Neoplastic Cells, Circulating
Breast Diseases
Neoplasm Metastasis
Neoplasms
Neoplasms by Site
Neoplastic Processes
Pathologic Processes
Skin Diseases
Everolimus
Sirolimus
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents
Immunologic Factors
Immunosuppressive Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on May 03, 2015