Anti-hormonal Therapie With Ribociclib in HR-positive / HER2- Negative Metastatic Breast Cancer

NCT03555877 | Completed Phase 2 DMC

• 1 other identifier: GBG 97
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multicenter, prospective, randomized, open-label, controlled phase II study to test the addition of the CDK4/6 inhibitor ribociclib to anti-hormonal treatment as maintenance therapy in patients with disease control (at least stable disease) after 1st line chemotherapy.

Conditions

Breast Cancer Metastatic

Keywords

Ribociclib; Anti-hormonal maintainance treatment; HR-positive; HER2-negative

Outcome Measures

Primary Outcomes (1)

• Locally-assessed progression-free survival (PFS)

  Primary efficacy endpoint is locally-assessed progression-free survival (PFS) defined as the time elapsed between randomization and tumor progression or death from any cause.

  Up to 39 months

Secondary Outcomes (5)

• The impact on overall survival

  Up to 39 months

• The clinical benefit rate

  Up to 39 months

• Patient reported outcomes

  Up to 39 months

• Number of participants with adverse events, serious adverse events and adverse events of special interest as assessed by CTCAE v4.03.

  Up to 33 months

• The number of patients who reduced, interrupted or permanently discontinued treatment and the reasons for that.

  Up to 33 months

Study Arms (2)

Anti-hormonal treatment + ribociclib

EXPERIMENTAL

In the experimental arm ribociclib will be dosed on a flat scale of 600mg/day (corresponding to three 200mg tablets once daily, 3 week on, one week off). Anti-hormonal/endocrine treatment of choice of investigator: anastrozole, exemestane, letrozole, fulvestrant.

Drug: Ribociclib; Drug: Anastrozole; Drug: Letrozole; Drug: Exemestane; Drug: Fulvestrant

Anti-hormonal treatment

ACTIVE COMPARATOR

In the control arm patients will receive endocrine treatment only (of choise of investigator). Anti-hormonal/endocrine treatment of choice of investigator: anastrozole, exemestane, letrozole, fulvestrant.

Drug: Anastrozole; Drug: Letrozole; Drug: Exemestane; Drug: Fulvestrant

Interventions

Ribociclib DRUG

Ribociclib in addition to endocrine maintenance therapy. Endocrine therapy, at the discretion of the investigator, could have already been started up to 4 weeks before randomization but not later than with first dose of ribociclib.

Also known as: Kisqali

Anti-hormonal treatment + ribociclib

Anastrozole DRUG

1mg once daily as indicated in the SmPC

Also known as: All marketed medicinal products with this active ingredient.

Anti-hormonal treatment; Anti-hormonal treatment + ribociclib

Letrozole DRUG

2,5mg once daily as indicated in the SmPC

Also known as: All marketed medicinal products with this active ingredient.

Anti-hormonal treatment; Anti-hormonal treatment + ribociclib

Exemestane DRUG

25mg once daily as indicated in the SmPC

Also known as: All marketed medicinal products with this active ingredient.

Anti-hormonal treatment; Anti-hormonal treatment + ribociclib

Fulvestrant DRUG

(prefilled syringes with fulvestrant 250mg each), 500mg given once a month, with an additional 500mg dose given two weeks after the first dose as indicated in the SmPC

Also known as: All marketed medicinal products with this active ingredient.

Anti-hormonal treatment; Anti-hormonal treatment + ribociclib

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent prior to beginning specific protocol procedures, including expected cooperation of the patients for the treatment and follow-up, must be obtained and documented according to the local regulatory requirements.
• Female patients.
• Age ≥ 18 years old.
• Histologically confirmed HER2-/HR+ locally advanced or metastatic invasive breast carcinoma assessed on the primary tumor and/or on the metastatic lesions (preferred).
• Willingness and ability to provide archived formalin fixed paraffin embedded tissue block or a partial block from primary surgery and/or tumor or metastasis biopsy, which will be used for further breast cancer research.
• Maintenance endocrine therapy could have already been started up to 6 weeks before randomization, but after achievement of tumor response or stable disease.
• Maintenance therapy must be preceded prior to randomization by at least 4 cycles of a mono- or polychemotherapy. Tumor response or stable disease needs to be maintained to allow entry into the trial. Study treatment must start within 8 weeks of the last dose of chemotherapy.
• Previous therapy with maximum one line of anti-hormonal treatment is allowed.
• Previous neoadjuvant/adjuvant therapy is allowed. In case of cancer other than breast cancer, treatment should be completed more than 5 years before study entry.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1.
• Resolution of all acute toxic effects of prior anti-cancer therapy or surgical procedures to NCI CTCAE version 4.03 Grade ≤ 1 (except alopecia or other toxicities not considered a safety risk for the patient at investigator's discretion).
• The patient must be accessible for scheduled visits, treatment and follow-up. Patients registered on this trial must be treated at the participating center which could be the Principal or a Co- investigator's site.
• Life-expectancy \> 6 months.
• The subjects need to be either A) of non-childbearing potential (documented postmenopausal or post hysterectomy) or B) childbearing potential with negative urinary pregnancy test (in this case patients need to use highly effective non-hormonal contraceptive).

You may not qualify if:

• Uncontrolled/untreated central nervous system lesions.
• Known severe hypersensitivity reactions to compounds similar to one of the investigational (active substance or peanut, soya or other excipients) and supportive treatment.
• Inadequate organ function immediate prior to randomization including:
• Hemoglobin \< 10 g/dL
• Absolute neutrophil count (ANC) \< 2000/mm³ (\< 2.0 x 109/L)
• Platelets \< 100,000/mm³ (\< 100 x 109/L)
• Alanine aminotransferase (ALAT/SGPT) and/or aspartate aminotransferase (ASAT/SGOT) \> 2.0 x upper normal limits (ULN). If the patient has liver metastases, ALT and AST should not be ≥5 ULN.
• Alkaline phosphatase (ALP) \> 2.5 x ULN
• Total serum bilirubin \> 1.5 x ULN
• Serum creatinine \>1.5 x ULN or estimated creatinine clearance \< 60 mL/min as calculated using the method standard for the Institution
• Severe and relevant comorbidity that would interact with the participation in the study.
• Previous malignant disease being disease-free for less than 5 years (except CIS of the cervix and non-melanomatous skin cancer).
• Evidence for active infection including wound infections and anamnestic HIV or hepatitis.
• QTc \>450 msec or a family or personal history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation, or Torsade de Pointes.
• Uncontrolled electrolyte disorders that can compound the effects of a QTc prolonging drug (i.e. hypocalcemia, hypokalemia, hypomagnesemia).

Sponsors & Collaborators

• GBG Forschungs GmbH: lead

Study Sites (1)

Studienzentrum Onkologie Ravensburg

Ravensburg, 88212, Germany

Location

Related Publications (2)

• Gligorov J, Doval D, Bines J, Alba E, Cortes P, Pierga JY, Gupta V, Costa R, Srock S, de Ducla S, Freudensprung U, Mustacchi G. Maintenance capecitabine and bevacizumab versus bevacizumab alone after initial first-line bevacizumab and docetaxel for patients with HER2-negative metastatic breast cancer (IMELDA): a randomised, open-label, phase 3 trial. Lancet Oncol. 2014 Nov;15(12):1351-60. doi: 10.1016/S1470-2045(14)70444-9. Epub 2014 Sep 28.

  PMID: 25273343 BACKGROUND

• Decker T, Ludtke-Heckenkamp K, Melnichuk L, Hirmas N, Lubbe K, Zahn MO, Schmidt M, Denkert C, Lorenz R, Muller V, Zahm DM, Mundhenke C, Bauer S, Thill M, Seropian P, Filmann N, Loibl S. Anti-hormonal maintenance treatment with the CDK4/6 inhibitor ribociclib after 1st line chemotherapy in hormone receptor positive / HER2 negative metastatic breast cancer: A phase II trial (AMICA). Breast. 2023 Dec;72:103575. doi: 10.1016/j.breast.2023.08.007. Epub 2023 Sep 1.

  PMID: 37690320 DERIVED

Related Links

• GBG website active studies

MeSH Terms

Interventions

ribociclib; Anastrozole; Letrozole; exemestane; Fulvestrant

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Thomas Decker, Prof. Dr.

  Gemeinschaftspraxis Onkologie Ravensburg

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 16, 2018
• First Posted: June 14, 2018
• Study Start: March 15, 2018
• Primary Completion: July 21, 2022
• Study Completion: July 21, 2022
• Last Updated: July 7, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)