DETECT IV - A Multicenter Single Arm Phase II Study to Investigate Clinical Efficacy of Everolimus in Combination With Endocrine Therapy in Postmenopausal Patients With Hormone-receptor+ve, HER2-ve MBC and Persisting HER2-ve CTCs

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 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 13, 2014
Last verified: January 2014
  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, single arm phase II study aimed at postmenopausal patients with hormone-receptor positive, HER2-negative MBC and exclusively HER2-negative CTCs. The primary objective of the trial is to estimate the clinical efficacy of the mTOR inhibitor everolimus in combination with endocrine therapy as assessed by progression-free survival (PFS). 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 in combination with standard endocrine therapy
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: DETECT IV - A Multicenter Single Arm Phase II Study to Investigate the Clinical Efficacy of Everolimus in Combination With Endocrine Therapy in Postmenopausal Patients With Hormone-receptor Positive, HER2-negative Metastatic Breast Cancer and Persisting HER2-negative Circulating Tumor Cells.

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

  • 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

  • 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)

  • 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


Estimated Enrollment: 400
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 Drug: Everolimus in combination with standard endocrine therapy

  Eligibility

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

Inclusion Criteria: 1. 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.

2. 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.

3. Indication for an endocrine therapy. (Histological confirmation of estrogen receptor positive (ER+) and/or progesterone receptor positive (PgR+) breast cancer) 4. Any endocrine therapy in the history is allowed. 5. 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).

7. HER2 negativity of all detected CTCs. HER2-negativity is defined as staining < HER2 3+.

8. Up to two lines of previous cytostatic treatment for MBC. 9. 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 10. 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 11. Written informed consent in study participation. 12. Undergoing a re-biopsy prior if tissue is accessible, which can be safely biopsied, is optional but desirable.

13. Tumor evaluation has been performed within 6 weeks before date of recruitment and results are available.

14. 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.

15. Age ≥ 18 years. 16. ECOG Performance Status ≤ 2.

Exclusion Criteria:

  1. Known hypersensitivity to everolimus or other mTOR inhibitors or to any of the other given drugs.
  2. Indication for treatment with chemotherapy.
  3. 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.
  4. Treatment with other investigational agents of any type or anticancer therapy during the trial, within 2 weeks prior to the start of treatment.
  5. Known HIV infection.
  6. 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).
  7. 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.
  8. Other malignant diseases within the last 3 years apart from CIN of the uterine cervix and skin basalioma.
  9. 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.
  10. Life expectancy < 3 months.
  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 13, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

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

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

ClinicalTrials.gov processed this record on September 30, 2014