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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03584009




Registration number
NCT03584009
Ethics application status
Date submitted
25/06/2018
Date registered
12/07/2018
Date last updated
28/06/2022

Titles & IDs
Public title
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
Scientific 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
Secondary ID [1] 0 0
2017-005118-74
Secondary ID [2] 0 0
WO40181
Universal Trial Number (UTN)
Trial acronym
Veronica
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Estrogen Receptor-positive (ER+)/Human Epidermal Growth Factor Receptor (HER2)-Negative Locally Advanced or Metastatic Breast Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Venetoclax
Treatment: Drugs - Fulvestrant

Experimental: Venetoclax + Fulvestrant - 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).

Active comparator: Fulvestrant - 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).


Treatment: Drugs: Venetoclax
Venetoclax was administered orally, 800-mg tablet beginning on Cycle 1 Day 1 until the 9th October 2020.

Treatment: Drugs: Fulvestrant
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
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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
Timepoint [1] 0 0
Randomization through till 6 months after the last participant is enrolled into the study (up to approximately 23 months)
Secondary outcome [1] 0 0
Progression Free Survival (PFS)
Timepoint [1] 0 0
Randomization through till 6 months after the last participant is enrolled into the study (up to approximately 23 months)
Secondary outcome [2] 0 0
Objective Response (OR)
Timepoint [2] 0 0
Randomization through till 6 months after the last participant is enrolled into the study (up to approximately 23 months)
Secondary outcome [3] 0 0
Duration of Response (DOR)
Timepoint [3] 0 0
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)
Secondary outcome [4] 0 0
Overall Survival (OS)
Timepoint [4] 0 0
Randomization to death from any cause, through till the end of the study (up to approximately 32 months)
Secondary outcome [5] 0 0
Percentage of Participants With Adverse Events (AEs)
Timepoint [5] 0 0
Baseline up until 28 days after the last dose of study drug (venetoclax or fulvestrant, whichever is later) up to approximately 32 months
Secondary outcome [6] 0 0
Plasma Concentrations of Venetoclax
Timepoint [6] 0 0
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)
Secondary outcome [7] 0 0
Plasma Concentrations of Fulvestrant (in Presence of Venetoclax)
Timepoint [7] 0 0
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)
Secondary outcome [8] 0 0
Plasma Concentrations of Fulvestrant (in Absence of Venetoclax)
Timepoint [8] 0 0
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)

Eligibility
Key inclusion criteria
* 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.
* 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

* 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.
* 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
6/09/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
6/05/2021
Sample size
Target
Accrual to date
Final
103
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Mater Hospital; Patricia Ritchie Centre for Cancer Care and Research - North Sydney
Recruitment hospital [2] 0 0
Mater Misericordiae Limited - South Brisbane
Recruitment hospital [3] 0 0
Peter MacCallum Cancer Center - North Melbourne
Recruitment postcode(s) [1] 0 0
2059 - North Sydney
Recruitment postcode(s) [2] 0 0
4101 - South Brisbane
Recruitment postcode(s) [3] 0 0
3051 - North Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Arkansas
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Hawaii
Country [7] 0 0
United States of America
State/province [7] 0 0
Kentucky
Country [8] 0 0
United States of America
State/province [8] 0 0
Maryland
Country [9] 0 0
United States of America
State/province [9] 0 0
Massachusetts
Country [10] 0 0
United States of America
State/province [10] 0 0
Minnesota
Country [11] 0 0
United States of America
State/province [11] 0 0
Nebraska
Country [12] 0 0
United States of America
State/province [12] 0 0
New Mexico
Country [13] 0 0
United States of America
State/province [13] 0 0
Ohio
Country [14] 0 0
United States of America
State/province [14] 0 0
South Dakota
Country [15] 0 0
United States of America
State/province [15] 0 0
Texas
Country [16] 0 0
United States of America
State/province [16] 0 0
Washington
Country [17] 0 0
Canada
State/province [17] 0 0
Ontario
Country [18] 0 0
Canada
State/province [18] 0 0
Quebec
Country [19] 0 0
Germany
State/province [19] 0 0
Aschaffenburg
Country [20] 0 0
Germany
State/province [20] 0 0
Erlangen
Country [21] 0 0
Germany
State/province [21] 0 0
Frankfurt
Country [22] 0 0
Germany
State/province [22] 0 0
Hamburg
Country [23] 0 0
Germany
State/province [23] 0 0
Muenchen
Country [24] 0 0
Germany
State/province [24] 0 0
Ravensburg
Country [25] 0 0
Germany
State/province [25] 0 0
Rostock
Country [26] 0 0
United Kingdom
State/province [26] 0 0
Bath
Country [27] 0 0
United Kingdom
State/province [27] 0 0
Brighton
Country [28] 0 0
United Kingdom
State/province [28] 0 0
London
Country [29] 0 0
United Kingdom
State/province [29] 0 0
Manchester
Country [30] 0 0
United Kingdom
State/province [30] 0 0
Nottingham

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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 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.
Trial website
https://clinicaltrials.gov/study/NCT03584009
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03584009