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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT03584009
Ethics application status
Date submitted
25/06/2018
Date registered
10/07/2018
Date last updated
7/02/2019

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
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

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

Experimental: Venetoclax + Fulvestrant - Participants in the venetoclax arm will receive venetoclax, taken orally and fulvestrant administered as IM injections until disease progression, unacceptable toxicity, withdrawal of consent, death, or predefined end of the study (2 years after the last patient is enrolled) which ever occur first.

Active Comparator: Fulvestrant - Participants will receive fulvestrant administered as IM (intramuscular) injections. No crossover to the venetoclax arm is permitted. Study treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, death, or predefined end of the study (2 years after the last patient is enrolled) which ever occur first.


Treatment: Drugs: Venetoclax
Venetoclax will be administered orally, 800-mg tablet beginning on Cycle 1 Day 1

Treatment: Drugs: Fulvestrant
Fulvestrant will be administered orally, 500 mg administered as two 250-mg intramuscular (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 Sudden Death (SD) lasting >= 24 weeks
Timepoint [1] 0 0
Randomization in patients with measurable disease at baseline through the end of study (2 years after the last patient is enrolled)
Secondary outcome [1] 0 0
Progression Free Survival (PFS) - (RECIST v1.1 ) Response Evaluation Criteria in Solid Tumors Version 1.1
Timepoint [1] 0 0
Randomization to the first occurrence of disease progression as determined by the investigator according to (RECIST v1.1 ) or death from any cause, until the end of study (2 years after the last patient is enrolled)
Secondary outcome [2] 0 0
Objective Response (OR)
Timepoint [2] 0 0
Objective Response defined as Complete Response (CR) or Partial response (PR), as determined by the investigator according to RECIST v1.1 from Randomization of patient until end of the study (2 years after the last patient enrolled)
Secondary outcome [3] 0 0
Duration of Response (DOR) - (as determined by the investigator according to RECIST v1.1)
Timepoint [3] 0 0
Time from first occurrence of a documented Objective response to the time of the first documented disease progression or death from any cause, whichever occurs first, until end of the study (2 years after the last patient enrolled)
Secondary outcome [4] 0 0
Overall Survival (OS)
Timepoint [4] 0 0
Randomization to death from any cause, through the end of study (2 years after the last patient enrolled)
Secondary outcome [5] 0 0
Percentage of participants with adverse events
Timepoint [5] 0 0
Baseline to end of study (2 years after the last patient enrolled)
Secondary outcome [6] 0 0
Plasma concentration of Venetoxclax and fulvestrant
Timepoint [6] 0 0
At pre-defined intervals from Cycle 1, Day 1, through end of treatment (2 years after the last patient enrolled).
Secondary outcome [7] 0 0
Mean changes from baseline scores in functional disease/treatment-related symptoms and global health status health-related quality of life (GHS/HRQoL) by cycle - Mean and mean changes will be assessed by the scales of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)
Timepoint [7] 0 0
Baseline, cycle 1 day 1, and all subsequent cycles through at the end of treatment/discontinuation visit (2 years after the last patient enrolled)
Secondary outcome [8] 0 0
Change in baseline pain score as assessed by the pain scale of EORTC QLQ-C30
Timepoint [8] 0 0
Baseline through end of study (2 years after the last patient enrolled)
Secondary outcome [9] 0 0
Baseline BCL-2 protein levels as measured by International Council for Harmonisation (IHC) correlating with clinical response measures
Timepoint [9] 0 0
Baseline through the end of study (2 years after the last patient enrolled)

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.

- Evidence of metastatic or locally advanced disease not amenable to surgical or local
therapy with curative intent

- Be postmenopausal

- 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 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 30 days after the last dose
of study drug

- Willing to provide tumor biopsy sample

- Have at least one measurable lesion via RECIST v1.1

- Have an Eastern Cooperative Oncology Group (ECOG) Performance Score of 0-1

- Have adequate organ and marrow function

- Have 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
Gender
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

- 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).

- Patients who are positive for HCV antibody must be negative for HCV by PCR to be
eligible for study participation. Patients 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 patients
must be willing to undergo monthly DNA testing

- Positive test results for hepatitis B core antibody (HBcAb) or hepatitis C virus (HCV)
antibody at screening

- Active HCV infection, defined as having a positive HCV antibody test at screening

- 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 patient'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

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
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
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 - 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
3000 - 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
France
State/province [19] 0 0
Lyon
Country [20] 0 0
France
State/province [20] 0 0
Paris
Country [21] 0 0
France
State/province [21] 0 0
Toulouse
Country [22] 0 0
Germany
State/province [22] 0 0
Aschaffenburg
Country [23] 0 0
Germany
State/province [23] 0 0
Erlangen
Country [24] 0 0
Germany
State/province [24] 0 0
Frankfurt
Country [25] 0 0
Germany
State/province [25] 0 0
Hamburg
Country [26] 0 0
Germany
State/province [26] 0 0
Muenchen
Country [27] 0 0
Germany
State/province [27] 0 0
Ravensburg
Country [28] 0 0
Germany
State/province [28] 0 0
Rostock
Country [29] 0 0
United Kingdom
State/province [29] 0 0
Bath
Country [30] 0 0
United Kingdom
State/province [30] 0 0
Brighton
Country [31] 0 0
United Kingdom
State/province [31] 0 0
London
Country [32] 0 0
United Kingdom
State/province [32] 0 0
Manchester
Country [33] 0 0
United Kingdom
State/province [33] 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, inoperable, locally advanced or MBC who experienced disease recurrence or
progression during or after treatment with CDK4/6i therapy for at least 8 weeks.
Trial website
https://clinicaltrials.gov/show/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
Reference Study ID Number: WO40181 www.roche.com/about_roche/roche_worldwide.htm
Address 0 0
Country 0 0
Phone 0 0
888-662-6728 (U.S. and Canada)
Fax 0 0
Email 0 0
global-roche-genentech-trials@gene.com
Contact person for scientific queries

No data has been provided for results reporting
Summary results
Not applicable