Clinical Trials /

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

NCT02035813

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: D-IV
  • SECONDARY ID: 2013-001269-18
  • NCT ID: NCT02035813

Conditions

  • HER2-negative Und Hormone-receptor Positive Metastatic Breast Cancer
  • HER2-negative Circulating Tumor Cells
  • Postmenopausal Female Patients

Interventions

DrugSynonymsArms
EverolimusAfinitorEverolimus in combination with standard endocrine therapy
EribulinHalavenEriubulin

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.

Trial Arms

NameTypeDescriptionInterventions
Everolimus in combination with standard endocrine therapyExperimentalPostmenopausal female patients with hormone-receptor positive, HER2-negative metastatic breast cancer with HER2-negative circulating tumor cells (CTCs) and indication for standard endocrine therapy.
  • Everolimus
EriubulinExperimentalPatients 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).
  • Eribulin

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression free survival (PFS)
Time Frame:8-12 weeks
Safety Issue:
Description:Time interval from randomization until progressive disease (PD) or death from any cause, whichever comes first

Secondary Outcome Measures

Measure:Overall response rate
Time Frame:8-12 weeks
Safety Issue:
Description:Rate of complete (CR) and partial responses (PR) in patients with whom target lesions were defined
Measure:Disease control rate (DCR)
Time Frame:8-12 weeks
Safety Issue:
Description:rate of patients who were assessed as having a PR or a CR or who had stable disease (SD) for at least 6 months
Measure:Overall survival (OS)
Time Frame:4 weeks
Safety Issue:
Description:Time from randomization until death of any cause
Measure:Dynamic of CTCs
Time Frame:8-12 weeks
Safety Issue:
Description:Descriptive statistics of regular CTC counts
Measure:For Everolimus cohort only: Levels of pS6
Time Frame:8-12 weeks
Safety Issue:
Description:Descriptive statistics of pS6 levels at baseline, at first radiological tumor assessment after about 12 weeks, and at the time of progression
Measure:For Everolimus cohort only: Change in the activation of the PI3K/Akt/mTOR-pathway in CTCs
Time Frame:8-12 weeks
Safety Issue:
Description: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)
Measure:For Everolimus cohort only: Estrogen-receptor 1 (ESR-1) mutations in CTCs
Time Frame:8-12 weeks
Safety Issue:
Description:Estrogen-receptor 1 (ESR-1) mutations in CTCs at baseline, after 12 weeks and at time of progression
Measure:For Eribulin cohort only: New metastasis-free survival (nMFS)
Time Frame:8-12 weeks
Safety Issue:
Description: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

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Prof. W. Janni

Trial Keywords

  • metastatic breast cancer
  • circulating tumor cells
  • everolimus
  • eribulin

Last Updated

June 6, 2017