DetectIV - Treatment of patients with advanced metastatic breast cancer and circulating blood cells devoid of Her2/neu.

Phase 1

• Conditions: Everolimus/ribociclib cohort (D-IVa):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.Eribulin cohort (D-IVb):Patients with hormone-receptor positive, HER2-negative metastatic breast cancer and indication to chemotherapy or patients with triple-negative metastatic breast cancer, both with HER2-negative circulating tumor cells (CTCs).; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2013-001269-18-DE
• Lead Sponsor: niversitätsklinikum Ulm (AöR)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2013-08-30
• Last Update Posted: 2 March 2022

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 300

Inclusion Criteria

In general:
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 fluorescent in situ hybridization (FISH) negative or just FISH negative, whichever was performed) in all tissue samples.
3.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).
4.HER2 negativity of all detected CTCs.
5.Adequate organ function within 7 days before date of recruitment.
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 desirable.
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.

Everolimus/ribociclib cohort (DIVa)
•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 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 (us-ing 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 limits with supplemets before the first dose of study medication:
-Sodium
-Potassium
-Total calcium

Eribulin cohort (DIVb)
•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 double barrier method, vasectomy of the sexual partner, complete sexual abstinence). Patient must consent in maintaining such contraception until 3 months after completion of study treatment
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adult

Exclusion Criteria

In general:
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. 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).
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.

Everolimus/Ribociclib cohort (DIVa)
•Known hypersensitivity to any of the excipients of ribociclib, everolimus or any of the other given drugs.
•Known hypersensitivity to lecithin (soya) and peanuts (ribocilib-cohort)
•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.

Eribulin cohort (DIVb)
•History of hypersensitivity reactions attributed to eribulin.
•Pre-existing neuropathy grade 3 or higher.
•Severe Congenital long QT syndrome.
•Pregnancy or nursing.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified