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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.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

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
What is being tested?
Venetoclax and Fulvestrant
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
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

Other trials in United States

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

Other trials in Germany

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

Other trials in United Kingdom

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

Other trials in Canada

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

Other trials in Australia

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 groups in NCT03584009
Study groupRoleWhat they receive
Venetoclax + FulvestrantExperimentalParticipants 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
FulvestrantActive comparatorParticipants 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.

  1. 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)

  1. 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)

  2. 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)

  3. 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)

  4. 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)

  5. 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

  6. 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)

  7. 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)

  8. 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.

  1. First posted12 Jul 2018
  2. Study start6 Sep 2018
  3. Primary completion5 Aug 2020
  4. Study completion6 May 2021

Why it stopped: Sponsor's decision, no safety concerns.

Resources

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)
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
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

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.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 28 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 40 sites in United States, Germany, United Kingdom, Canada, Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Sep 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 (time frame: Randomization through till 6 months after the last participant is enrolled into the study (up to approximately 23 months)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03584009.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jun 2022.

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