Metronomic vinorelbin, cyclophosphamide and capecitabine after progression to cyclin-dependent kinase 4/6 inhibitors for hormone receptors positive HER2 negative metastatic breast cancer

Phase 1

• Conditions: HER2 negative hormone receptors positive metastatic breast cancer progressed after CDK 4/6 inhibitors; MedDRA version: 21.0Level: LLTClassification code 10007310Term: Carcinoma breast stage IVSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2020-003435-13-IT
• Lead Sponsor: FONDAZIONE POLICLINICO UNIVERSITARIO AGOSTINO GEMELLI IRCCS UNIVERSITA' CATTOLICA DEL SACRO CUORE

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-06-04
• Last Update Posted: 30 August 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 25

Inclusion Criteria

-Male or female subjects with any menopausal status age = 18 years and has signed informed consent before any trial related activities are conducted;
-Subjects with histologically or cytologically proven diagnosis of adenocarcinoma of the breast with evidence of either locally advanced disease not amenable to resection or radiation therapy with curative intent or metastatic disease not amenable to curative therapy;
-Subjects must have ER-positive and/or PgR-positive, HER2-negative tumor status confirmed per local laboratory testing on their primary tumor or if available on their most recent biopsy from a metastatic lesion (if metastatic disease), or recurrent disease lesion (if locally advanced).
-Subjects must have one of the following as defined by RECIST v1.1 prior to start study treatment:
a.Measurable disease as per RECIST 1.1 criteria.
b.Non measurable (evaluable) bone-only disease.
-Subjects must be progressed on/after prior CDK4/6 inhibitor combination therapy with either fulvestrant or an AI and it must be the last therapy before the study entry;
-Subjects must not be candidates to further endocrine therapies or other combinations;
-Subjects may have previously received at least one and no more than two lines of endocrine therapy for advanced/metastatic breast cancer and meet the following criteria:
a.Last endocrine therapy to study entry must be given in combination with CDK4/6i;
b.Progression on or within eight weeks of ending treatment with each prior line of endocrine therapy (single agent or in combination) must be documented;
c.For subjects who progress during or within 12 months of adjuvant endocrine therapy, this may count as one line of treatment for advanced/metastatic disease;
d.In the absence of progression, adjuvant therapy does not count as one of the lines of endocrine therapy;
e.Endocrine therapy must be discontinued prior to study entry, excluding LH-RH analogue;
-Subjects may have received no more than one line of chemotherapy in the advanced/metastatic setting;
-Patients may have received any primary and/or adjuvant therapies. For subjects who progress within 12 months of (neo)adjuvant chemotherapy, this will count as one prior line of therapy for advanced/metastatic disease;
-Patients may have received metronomic capecitabine, methotrexate and cyclophosphamide or standard dose capecitabine in adjuvant setting at least 12 months before study entry;
-Previous treatment with capecitabine, cyclophosphamide and vinorelbine not in metronomic schedule for advanced disease is allowed, provided that the patient has progressive disease at study entry and the patients should not be defined as refractory” to treatments (PR o CR o SD > 6 months);
-Eastern Cooperative Oncology Group (ECOG) performance status = 2;
-Life expectancy of at least 12 weeks;
-Able to to swallow the study drug whole as a tablet
-Patient has adequate bone marrow and organ function;
-Confirmed negative serum pregnancy test (ß-hCG) within 72 hours before starting study treatment for patients with pre or peri-menopausal status.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 15
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion Criteria

1. Previous metronomic chemotherapy for advanced disease with capecitabine, cyclophosphamide and vinorelbine;
2. Patients defined as refractory” to capecitabine, cyclophosphamide and vinorelbine (PD o SD < 6 months);
3. Presence of symptomatic cerebral or leptomeningeal involvement;
4. Previous or concomitant other malignancy except basal or squamous cell carcinoma of the skin or adequately treated in situ carcinoma of the cervix;
5. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements;
6. Malabsorption syndrome or disease affecting significantly gastrointestinal function or major resection of the stomach or proximal small bowel that could affect absorption of oral vinorelbine;
7. Patients with known low or absent dihydropyrimidine dehydrogenase (DPD) activity;
8. History of severe and unexpected reactions to fluoropyrimidine therapy;
9. Concurrent treatment with any other anti-cancer therapy except LHRH analogue;
10. Patients with pre-existing motor or sensory peripheral neuropathy grade 2 according to National Cancer Institute criteria;
11. Major surgery within 28 days before the first dose of study drug;
12. Radiation therapy within 14 days (28 days for brain lesions per Exclusion Criterion 3) before the first dose of study drug. Note: tumor lesions previously subjected to radiation therapy or other locoregional therapy will be considered measurable only if disease progression after completion of locoregional therapy is clearly documented;
13. Any concurrent severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with compliance with study procedures or the interpretation of study results and, in the judgment of the Investigator, would make the subject inappropriate for entry into this study;
14. Known hypersensitivity reaction to drugs chemically related to capecitabine, cyclophosphamide and vinorelbine or their excipients;
15. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test;
16. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are willing to use highly effective methods of birth control as determined to be acceptable by the principal investigator and sponsor during the study treatment and through 120 days after the last dose of study drug.

Study & Design

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