Estrogen Receptor-positive (ER+)/Human Epidermal Growth Factor Receptor (HER2)-Negative Locally Advanced or Metastatic Breast CancerPhase 2VeronicaNCT03584009
A Phase II Study Comparing The Efficacy Of Venetoclax + Fulvestrant Vs. Fulvestrant In Women With Estrogen Receptor-Positive, Her2-Negative Locally Advanced Or Metastatic Breast Cancer Who Experienced Disease Recurrence Or Progression During Or After CDK4/6 Inhibitor Therapy
A Phase 2 study testing Venetoclax and Fulvestrant in people with Estrogen Receptor-positive (ER+)/Human Epidermal Growth Factor Receptor (HER2)-Negative Locally Advanced or Metastatic Breast Cancer, run by Hoffmann-La Roche at 40 sites in 5 countries.
Trial summary
This is a Phase II, multicenter, open-label, randomized study to compare the efficacy of venetoclax in combination with fulvestrant compared with fulvestrant alone in women with ER+, HER2-negative, locally advanced or Metastatic Breast Cancer (MBC) who experienced disease recurrence or progression during or after… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Estrogen Receptor-positive (ER+)/Human Epidermal Growth Factor Receptor (HER2)-Negative Locally Advanced or Metastatic Breast Cancer
- What is being tested?
- Venetoclax and Fulvestrant
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 103 participants
- Where
- 40 sitesin 5 countries
- Study dates
- 6 Sep 2018to 6 May 2021
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histological or cytological confirmation of estrogen receptor-positive (ER+) invasive carcinoma of the breast. ER+, HER2- negative invasive carcinoma of the breast with evaluable sample for BCL-2 IHC value at the time of screening. Participants who were originally diagnosed with HER2-positive breast cancer that converted to HER2-negative MBC are not eligible.
- Evidence of metastatic or locally advanced disease not amenable to surgical or local therapy with curative intent.
- Be postmenopausal or pre- or perimenopausal women amenable to being treated with the luteinizing hormone-releasing hormone (LHRH) agonist goserelin.
- Participants must not have received more than two prior lines of hormonal therapy in the locally advanced or metastatic setting. In addition, at least one line of treatment must be a CDK4/6i AND participants must have experienced disease recurrence or progression during or after CDK4/6i therapy, which must have been administered for a minimum of 8 weeks prior to progression.
- Participants for whom endocrine therapy (e.g., fulvestrant) is recommended and treatment with cytotoxic chemotherapy is not indicated at the time of entry into the study, as per national or local treatment guidelines.
- Women of childbearing potential (i.e., not postmenopausal for at least 12 months or surgically sterile) must have had a negative serum pregnancy test result at screening, within 14 days prior to the first study drug administration.
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- For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use non-hormonal contraceptive methods with a failure rate of <1% per year during the treatment period and for up to 2 years after the last dose of study drug (or based on the local prescribing information for fulvestrant). Women must refrain from donating eggs during this same period.
- Willing to provide tumor biopsy sample.
- Had at least one measurable lesion via RECIST v1.1.
- Had an Eastern Cooperative Oncology Group (ECOG) Performance Score of 0-1.
- Had adequate organ and marrow function.
- Had a life expectancy > 3 months.
- To full fill the coagulation requirements for patient with or without therapeutic anticoagulation.
Who cannot join
- Prior treatment with fulvestrant or other selective estrogen receptor degraders (SERDs), venetoclax, or any agent whose mechanism of action is to inhibit BCL-2.
- Pregnant, lactating, or intending to become pregnant during the study.
- Known untreated or active Central Nervous System (CNS) metastases (progressing or requiring anticonvulsants or corticosteroids for symptomatic control.
- Prior chemotherapy in the locally advanced or metastatic setting regardless of the duration of the treatment.
- Any anti-cancer therapy received within 21 days of the first dose of study drug, including chemotherapy, radiotherapy, hormonal therapy, immunotherapy, antineoplastic vaccines, or other investigational therapy. (Radiotherapy with palliative intent to non-target sites is allowed).
- Concurrent radiotherapy to any site or prior radiotherapy within 21 days of Cycle 1 Day 1 or previous radiotherapy to the target lesion sites (the sites that are to be followed for determination of a response) or prior radiotherapy to > 25% of bone marrow.
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- Current severe, uncontrolled, systemic disease (e.g., clinically significant cardiovascular, pulmonary, metabolic or infectious disease.
- Any major surgery within 28 days of the first dose of study drug or anticipation of the need for major surgery during the course of study treatment.
- Consumption of one or more of the following within 3 days prior to the first dose of study drug: Grapefruit or grapefruit products; Seville oranges including marmalade containing Seville oranges; Star fruit (carambola).
- Administration within 7 days prior first dose of study treatment of Steroid therapy for anti-neoplastic intent, Strong or moderate CYP3A inhibitors or Strong or moderate CYP3A inducers.
- Need for current chronic corticosteroid therapy (> 10 mg of prednisone per day or an equivalent dose of other anti-inflammatory corticosteroids).
- Known infection with (human immunodeficiency virus) HIV or human T-cell leukemia virus 1.
- Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment, or any major episode of infection requiring treatment with IV antibiotics or hospitalization (relating to the completion of the course of antibiotics) within 4 weeks prior to Cycle 1 Day).
- Positive test results for hepatitis B core antibody (HBcAb) or hepatitis C virus (HCV) antibody at screening. Participants who were positive for HCV antibody should have been negative for HCV by PCR to be eligible for study participation. Participants with a past or resolved hepatitis B virus (HBV) infection (defined as having a positive total HBcAb and negative hepatitis B surface antigen [HbsAg]) may be included if HBV DNA is undetectable. These participants should have been willing to undergo monthly DNA testing.
- Participants who had a positive HCV antibody test are eligible for the study if a PCR assay is negative for HCV RNA.
- History of other malignancies within the past 5 years except for treated skin basal cell carcinoma, squamous cell carcinoma, non-malignant melanoma <= 1.0 mm without ulceration, localized thyroid cancer, or cervical carcinoma in-situ.
- Administration of a live, attenuated vaccine within 4 weeks prior to initiation of study treatment or anticipation of need for such a vaccine during the study.
- Cardiopulmonary dysfunction.
- Other medical or psychiatric conditions that, in the opinion of the investigatory, may interfere with the participant's participation in the study.
- Inability or unwillingness to swallow pills or receive intramuscular (IM) injections.
- History of malabsorption syndrome or other condition that would interfere with enteral absorption.
- History of inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis) or active bowel inflammation (e.g., diverticulitis).
- Concurrent hormone replacement therapy.
- Inability to comply with study and follow-up procedures.
- History or active cardiopulmonary dysfunction.
- Known hypersensitivity to any of the study medications (fulvestrant, venetoclax) or to any of the excipients.
Trial locations and contacts
40 sites in 5 countries.
40 sites in 5 countries
United States21 sites
University of New Mexico Cancer Center
Albuquerque, New Mexico, 87131
Ashland-Bellefonte Cancer Center
Ashland, Kentucky, 41101-7016
University of Maryland Medical Center
Baltimore, Maryland, 21201
Massachusetts General Hospital.
Boston, Massachusetts, 02114
Cleveland Clinic
Cleveland, Ohio, 44195
The University of Texas Southwestern Medical Center at Dallas
Dallas, Texas, 75390
Providence Regional Cancer Partnership
Everett, Washington, 98201
The Center for Cancer and Blood Disorders - Fort Worth
Fort Worth, Texas, 76104
Kaiser Permanente - Moanalua Medical Center
Honolulu, Hawaii, 96819-1469
Millennium Research & Clinical Development
Houston, Texas, 77090
UC San Deigo Moores Cancer Center
La Jolla, California, 92037
Nebraska Hematology Onco, PC
Lincoln, Nebraska, 68506
Northwest Georgia Oncology Centers PC - Marietta
Marietta, Georgia, 30060
Sylvester Comprehensive Cent.
Miami, Florida, 33136
Abbott Northwestern Hospital
Minneapolis, Minnesota, 55407
Comprehensive Cancer Center at Desert Regional Medical Center
Palm Springs, California, 92262
Mass General/North Shore Cancer
Peabody, Massachusetts, 01960
Mayo Clinic Hospital
Phoenix, Arizona, 85054
St. Joseph Health Medical Group - Annadel Medical Group
Santa Rosa, California, 95403-1757
Sanford Health System
Sioux Falls, South Dakota, 57105
Highlands Oncology Group
Springdale, Arkansas, 72762
Germany7 sites
Hämato-Onkologische Schwerpunktpraxis am Klinikum Aschaffenburg
Aschaffenburg, 63739
Universitätsklinikum Erlangen; Frauenklinik
Erlangen, 91054
Klinikum Frankfurt Höchst GmbH
Frankfurt, 65929
Facharztzentrum Eppendorf, Studien GbR
Hamburg, 20249
Rotkreuzklinikum München; Frauenklinik
München, 80637
Gemeinschaftspraxis für Hämatologie und Onkologie GbR; Dechow & Decker & Nonnenbroich
Ravensburg, 88212
Klinikum Südstadt Rostock
Rostock, 18059
United Kingdom5 sites
Royal United Hospital Bath NHS Trust
Bath, BA1 3NG
Royal Sussex County Hospital
Brighton, BN2 5BE
Barts Health NHS Trust - St Bartholomew's Hospital
London, EC1A 7BE
The Christie NHS Foundation Trust
Manchester, M20 4BX
Nottingham University Hospitals NHS Trust - City Hospital
Nottingham, NG5 1PB
Canada4 sites
Southlake Regional Health Center
Newmarket, Ontario, L3Y 2R2
The Ottawa Hospital
Ottawa, Ontario, K1H 8L6
Centre Hospitalier Universitaire de Sherbrooke - Hopital Fleurimont
Sherbrooke, Quebec, J1H 5N4
Sunnybrook Health Sciences Centre
Toronto, Ontario, M4N 3M5
Australia3 sites
Peter MacCallum Cancer Center
North Melbourne, Victoria, 3051
Mater Hospital; Patricia Ritchie Centre for Cancer Care and Research
North Sydney, New South Wales, 2059
Mater Misericordiae Limited
South Brisbane, Queensland, 4101
About this study
Official title: A Phase II, Multicenter, Randomized Study To Compare The Efficacy Of Venetoclax Plus Fulvestrant Versus Fulvestrant In Women With Estrogen Receptor-Positive, Her2-Negative Locally Advanced Or Metastatic Breast Cancer Who Experienced Disease Recurrence Or Progression During Or After CDK4/6 Inhibitor Therapy
This is a Phase II, multicenter, open-label, randomized study to compare the efficacy of venetoclax in combination with fulvestrant compared with fulvestrant alone in women with ER+, HER2-negative, locally advanced or Metastatic Breast Cancer (MBC) who experienced disease recurrence or progression during or after treatment with CDK4/6i therapy for at least 8 weeks. As of 9th October 2020, participants in the Venetoclax + Fulvestrant arm, have all discontinued Venetoclax treatment and have continued on Fulvestrant treatment alone.
- Being tested
- Venetoclax, Fulvestrant
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VenetoclaxDrug
Venetoclax was administered orally, 800-mg tablet beginning on Cycle 1 Day 1 until the 9th October 2020.
FulvestrantDrug
Fulvestrant was administered orally, 500 mg administered as two 250-mg IM injections on Cycle 1 Days 1 and 15 and on Day 1 of each subsequent 28-day cycle
| Study group | Role | What they receive |
|---|---|---|
| Venetoclax + Fulvestrant | Experimental | Participants were administered Venetoclax 800mg orally once daily (QD) and Fulvestrant 500mg intramuscularly (IM) on Day 1 and 15 of Cycle 1 and Day 1 of subsequent cycles (Cycle length = 28 days). Receives: Drug: Venetoclax; Drug: Fulvestrant |
| Fulvestrant | Active comparator | Participants were administered Fulvestrant 500mg only IM on Day 1 and 15 of Cycle 1 and Day 1 of subsequent cycles (Cycle length = 28 days). Receives: Drug: Fulvestrant |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical Benefit Defined as Complete Response (CR), Partial Response (PR) or Stable Disease (SD) Lasting >= 24 Weeks, as Determined by the Investigator According to RECIST v1.1
Clinical Benefit was defined as CR, PR, or SD lasting more than equal to 24 weeks from randomization in participants with measurable disease at baseline, as determined by the investigator according to Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.1. Per RECIST v1.1 for target lesions assessed by CT or MRI: CR, Disappearance of all target lesions; PR, PR >= 30% decrease in the sum of diameters of target lesions (TL) taking as reference the baseline sum of diameters; SD, neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Disease Progression (PD), PD>= 20% increase in the sum of diameters of TL taking as reference the smallest sum on study(Nadir). In addition to the relative increase of 20% sum must have demonstrate an absolute increase of at least 5mm.
Measured: Randomization through till 6 months after the last participant is enrolled into the study (up to approximately 23 months)
Secondary outcomes (8)
Progression Free Survival (PFS)
PFS was defined as the time from randomization to the first occurrence of disease progression (as determined by the investigator according to RECIST v1.1) or death from any cause, whichever occurs first.
Measured: Randomization through till 6 months after the last participant is enrolled into the study (up to approximately 23 months)
Objective Response (OR)
OR was defined as CR or PR, in participants with measurable disease at baseline as determined by the investigator according to RECIST v1.1.
Measured: Randomization through till 6 months after the last participant is enrolled into the study (up to approximately 23 months)
Duration of Response (DOR)
DOR was defined as the time from the first occurrence of a documented objective response to the time of the first documented disease progression (as determined by the investigator according to RECIST v1.1) or death from any cause, whichever occurs first.
Measured: Time from first occurrence of a documented objective response to the first documented disease progression or death from any cause, whichever occurs first, until 6 months after the last participant is enrolled in the study (up to approximately 23 months)
Overall Survival (OS)
OS was defined as the time from randomization to death due to any cause.
Measured: Randomization to death from any cause, through till the end of the study (up to approximately 32 months)
Percentage of Participants With Adverse Events (AEs)
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including abnormal laboratory values or abnormal clinical test results), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study were also considered as AEs.
Measured: Baseline up until 28 days after the last dose of study drug (venetoclax or fulvestrant, whichever is later) up to approximately 32 months
Plasma Concentrations of Venetoclax
Measured: Cycle 1 Day 1: 4 hours (hrs) post-dose; Cycle 2 Day 1: pre-dose (within 1 hr) and 2, 4, 6, 8 hrs post-dose; any time during visits up to study drug discontinuation/Early Termination (up to approximately 32 months)
Plasma Concentrations of Fulvestrant (in Presence of Venetoclax)
Measured: Cycle 2 Day 1: pre-dose (within 1 hr); Cycle 6 Day 1: pre-dose (within 1 hr); any time during visits up to study drug discontinuation/Early Termination (up to approximately 32 months)
Plasma Concentrations of Fulvestrant (in Absence of Venetoclax)
Measured: Cycle 2 Day 1: pre-dose (within 1 hr); any time during visits up to study drug discontinuation/Early Termination (up to approximately 32 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2018
- Study start6 Sep 2018
- Primary completion5 Aug 2020
- Study completion6 May 2021
Why it stopped: Sponsor's decision, no safety concerns.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Estrogen Receptor-positive (ER+)/Human Epidermal Growth Factor Receptor (HER2)-Negative Locally Advanced or Metastatic Breast CancerStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 103 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03584009
- Sponsor's protocol ID
- WO40181
- Other IDs
- 2017-005118-74, 2017
- Acronym
- Veronica
- Status last verified
- Jun 2022
- First submitted
- 25 Jun 2018
- Last updated
- 28 Jun 2022
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No