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

• ClinicalTrials.gov Identifier: NCT02035813
• Recruitment Status: Recruiting
• First Posted: January 14, 2014
• Last Update Posted: October 25, 2019
• Sponsor: Prof. W. Janni
• Information provided by (Responsible Party): Prof. W. Janni, University of Ulm

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
HER2-negative and Hormone-receptor Positive Metastatic Breast Cancer; HER2-negative Circulating Tumor Cells; Postmenopausal Female Patients	Drug: Ribociclib; Drug: Eribulin	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 300 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (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).
• Study Start Date: January 2014
• Estimated Primary Completion Date: December 2020
• Study Completion Date: December 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Ribociclib 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: Ribociclib; Ribociclib/Everolimus in combination with endocrine therapy; Other Name: Kisqali
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

Outcome Measures

Primary Outcome Measures :

1. Progression free survival (PFS) [ Time Frame: 8-12 weeks ]
   Time interval from randomization until progressive disease (PD) or death from any cause, whichever comes first

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

Both cohorts:

• 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.
• 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 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
• Everolimus cohort:
• Cholesterol ≤ 2.0 × ULN
• Ribociclib cohort:
• Standard 12-lead ECG values assessed by the local laboratory:
• - QTcF interval at screening < 450 msec (using Fridericia's correction)
• - Resting heart rate 50-90 bpm
• INR ≤ 1,5 (ribocilclib cohort)
• Patients must have the following laboratory values within normal limits or corrected to within normal lim-its with supplemets before the first dose of study medication:
• -Sodium
• -Potassium
• -Total calcium

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/Ribociclib only:

• Known hypersensitivity to any of the excipients of ribociclib, everolimus or any of the other given drugs.
• Known hypersensitivity to lecithin (soya) and pea-nuts (ribocilib-cohort)
• 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

Contacts

Contact: Sabrina Krause, M. sc.; sabrina.krause@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:

Related Info 

• Responsible Party: Prof. W. Janni, University hospital Ulm - Department of Gynecology, University of Ulm
• ClinicalTrials.gov Identifier: NCT02035813
• Other Study ID Numbers: D-IV; 2013-001269-18 ( EudraCT Number )
• First Posted: January 14, 2014
• Last Update Posted: October 25, 2019
• Last Verified: October 2019

Keywords provided by Prof. W. Janni, University of Ulm:

metastatic breast cancer; circulating tumor cells; eribulin; ribociclib

Additional relevant MeSH terms:

Breast Neoplasms; Neoplastic Cells, Circulating; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Neoplasm Metastasis; Neoplastic Processes; Pathologic Processes