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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05909397




Registration number
NCT05909397
Ethics application status
Date submitted
25/05/2023
Date registered
18/06/2023
Date last updated
6/06/2024

Titles & IDs
Public title
A Study of ARV-471 (PF-07850327) Plus Palbociclib Versus Letrozole Plus Palbociclib in Participants With Estrogen Receptor Positive, Human Epidermal Growth Factor Negative Advanced Breast Cancer
Scientific title
A PHASE 3, RANDOMIZED, OPEN-LABEL, MULTICENTER STUDY OF ARV-471(PF-07850327) PLUS PALBOCICLIB VERSUS LETROZOLE PLUS PALBOCICLIB FOR THE TREATMENT OF PARTICIPANTS WITH ESTROGEN RECEPTOR-POSITIVE, HER2-NEGATIVE BREAST CANCER WHO HAVE NOT RECEIVED ANY PRIOR SYSTEMIC ANTI-CANCER TREATMENT FOR ADVANCED DISEASE (VERITAC-3)
Secondary ID [1] 0 0
2022-500545-24-00
Secondary ID [2] 0 0
C4891002
Universal Trial Number (UTN)
Trial acronym
VERITAC-3
Linked study record

Health condition
Health condition(s) or problem(s) studied:
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 - ARV-471 (PF-07850327)
Combination Product - Palbociclib
Treatment: Drugs - Letrozole
Combination Product - Palbociclib

Experimental: Arm A (Investigational Arm) - Participants will receive:
ARV-471, orally, once daily, continuously, in a 28-day cycle, plus
Palbociclib, orally, once daily for 21 consecutive days followed by 7 days off treatment in a 28 day cycle

Active Comparator: Arm B (Comparator Arm): - Participants will receive:
Letrozole, orally, once daily, continuously, in a 28-day cycle, plus
Palbociclib, orally, once daily for 21 consecutive days followed by 7 days off treatment, in a 28-day cycle.


Treatment: Drugs: ARV-471 (PF-07850327)
Pharmaceutical form: Tablets. Route of Administration: Oral

Combination Product: Palbociclib
Pharmaceutical form: Capsules. Route of Administration: Oral.

Treatment: Drugs: Letrozole
Pharmaceutical form: Capsules. Route of Administration: Orally

Combination Product: Palbociclib
Pharmaceutical form: Capsules. Route of Administration: Oral.
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Combination Product
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Study Lead-in (SLI): Incidence of Grade 4 neutropenia
Timepoint [1] 0 0
From randomization date up to Cycle 4 (each cycle is 28 days).
Primary outcome [2] 0 0
SLI: Incidence of dose reduction
Timepoint [2] 0 0
From randomization date up to Cycle 4 (each cycle is 28 days).
Primary outcome [3] 0 0
SLI: Incidence of drug discontinuation.
Timepoint [3] 0 0
From randomization date up to Cycle 4 (each cycle is 28 days).
Primary outcome [4] 0 0
Phase 3: Progression-Free Survival
Timepoint [4] 0 0
From randomization date, every 12 weeks, to date of first documentation of progression or death, up to approximately 4 years.
Secondary outcome [1] 0 0
SLI and Phase 3. Objective Response Rate
Timepoint [1] 0 0
From randomization date, every 12 weeks, to the date of progression or death (up to approximately 4 years).
Secondary outcome [2] 0 0
SLI and Phase 3: Duration of Response
Timepoint [2] 0 0
From the date of the first objective response, every 12 weeks, to the date of disease progression or death (up to approximately 4 years).
Secondary outcome [3] 0 0
SLI and Phase 3: Clinical Benefit Rate
Timepoint [3] 0 0
Every 12 weeks From randomization date, every 12 week, to the date of progression or death (up to approximately 4 years).
Secondary outcome [4] 0 0
Phase 3: Overall Survival
Timepoint [4] 0 0
From randomization date, every 3 months, to date of death (up to approximately 6 years)
Secondary outcome [5] 0 0
SLI and Phase 3: Incidence of Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Timepoint [5] 0 0
From baseline to date to end of treatment (up to approximately 4 years)
Secondary outcome [6] 0 0
SLI and Phase 3: Incidence of laboratory abnormalities
Timepoint [6] 0 0
From baseline to end of treatment (up to approximately 4 years)
Secondary outcome [7] 0 0
SLI and Phase 3: Incidence of Electrocardiogram (ECG) Abnormalities
Timepoint [7] 0 0
From baseline up to the end of treatment (up to approximately 4 years)
Secondary outcome [8] 0 0
SLI and Phase 3: Plasma concentrations of ARV-471 and palbociclib
Timepoint [8] 0 0
From randomization date up to Cycle 5 (each cycle is 28 days)
Secondary outcome [9] 0 0
Phase 3: Health state utility and health status will be assessed using the European Quality of Life Group questionnaire with 5 dimensions and 5 levels per dimension (EQ-5D-5L)
Timepoint [9] 0 0
From baseline, each cycle up to cycle 3, then every odd cycle to end of treatment (up to approximately 4 years). Each cycle is 28 days
Secondary outcome [10] 0 0
Phase 3: Disease-related Quality of Life will be assessed using the European Organization for Research and Treatment of Cancer (EORTC) core quality of life questionnaire (QLQ-C30)
Timepoint [10] 0 0
From baseline, each cycle up to Cycle 3, then every odd cycle to end of treatment (up to approximately 4 years). Each cycle is 28 days.
Secondary outcome [11] 0 0
Phase 3: Disease- and treatment-related Quality of Life will be assessed using the European Organization for Research and Treatment of Cancer (EORTC) breast cancer module (QLQ-BR23) questionnaire.
Timepoint [11] 0 0
From baseline, each cycle up to Cycle 3, then every odd cycle to end of treatment (up to approximately 4 years). Each cycle is 28 days.
Secondary outcome [12] 0 0
Phase 3: Changes from baseline in plasma ctDNA (Circulating Deoxyribonucleic Acid)
Timepoint [12] 0 0
From baseline to end of treatment (up to approximately 4 years)

Eligibility
Key inclusion criteria
- Adult participants with loco-regional recurrent or metastatic disease not amenable to
curative treatment

- Confirmed diagnosis of ER+/HER2- breast cancer

- No prior systemic treatment for loco-regional recurrent or metastatic disease

- Measurable disease evaluable per Response Evaluation Criterion in Solid Tumors
(RECIST) v.1.1 or non-measurable bone-only disease

- Eastern Cooperative Oncology Group (ECOG) performance status 0-2

- Phase 3 only: Participants should be willing to provide blood and tumor tissue
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Disease recurrence while on, or within 12 months of completion of adjuvant endocrine
therapy

- Prior treatment with cyclin dependent kinase 4/6 inhibitors (CDK4/6i), fulvestrant,
elacestrant and other investigational drugs including novel endocrine therapies, any
selective estrogen receptor degraders (SERDs), covalent antagonists (SERCAs) and
complete ER antagonists (CERANs).

- Inadequate liver, kidney and bone marrow function

- Impaired cardiovascular function or clinically significant cardiovascular diseases

- Refractory nausea and vomiting, inability to swallow capsules and tablets whole,
chronic gastrointestinal diseases, significant gastric (total or partial) or bowel
resection that would preclude adequate absorption of study interventions.

- Current use or anticipated need for food, herbal supplements or drugs that are known
strong CYP3A4 inhibitors or inducers.

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 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
9/08/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
26/07/2030
Actual
Sample size
Target
Accrual to date
Final
1180
Recruitment in Australia
Recruitment state(s)
SA,VIC
Recruitment hospital [1] 0 0
Cancer Research SA - Adelaide
Recruitment hospital [2] 0 0
Cabrini Hospital -Brighton - Brighton
Recruitment hospital [3] 0 0
Barwon Health - Geelong
Recruitment hospital [4] 0 0
Cabrini Hospital - Malvern - Malvern
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
3186 - Brighton
Recruitment postcode(s) [3] 0 0
3220 - Geelong
Recruitment postcode(s) [4] 0 0
3144 - Malvern
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Florida
Country [2] 0 0
United States of America
State/province [2] 0 0
Michigan
Country [3] 0 0
United States of America
State/province [3] 0 0
Missouri
Country [4] 0 0
United States of America
State/province [4] 0 0
Tennessee
Country [5] 0 0
United States of America
State/province [5] 0 0
Virginia
Country [6] 0 0
Brazil
State/province [6] 0 0
Espírito Santo
Country [7] 0 0
Brazil
State/province [7] 0 0
RIO Grande DO SUL
Country [8] 0 0
Brazil
State/province [8] 0 0
SÃO Paulo
Country [9] 0 0
China
State/province [9] 0 0
Beijing
Country [10] 0 0
China
State/province [10] 0 0
Guangdong
Country [11] 0 0
China
State/province [11] 0 0
Hubei
Country [12] 0 0
China
State/province [12] 0 0
Shaanxi
Country [13] 0 0
China
State/province [13] 0 0
Zhejiang
Country [14] 0 0
Hungary
State/province [14] 0 0
Debrecen
Country [15] 0 0
Italy
State/province [15] 0 0
Campania
Country [16] 0 0
Italy
State/province [16] 0 0
Emilia-romagna
Country [17] 0 0
Italy
State/province [17] 0 0
Lombardia
Country [18] 0 0
Japan
State/province [18] 0 0
Aichi
Country [19] 0 0
Japan
State/province [19] 0 0
Chiba
Country [20] 0 0
Japan
State/province [20] 0 0
Tokyo
Country [21] 0 0
Slovakia
State/province [21] 0 0
Partizanske
Country [22] 0 0
Slovakia
State/province [22] 0 0
Presov
Country [23] 0 0
Spain
State/province [23] 0 0
Barcelona [barcelona]
Country [24] 0 0
Spain
State/province [24] 0 0
Catalunya [cataluña]
Country [25] 0 0
Spain
State/province [25] 0 0
Jaén
Country [26] 0 0
Spain
State/province [26] 0 0
Málaga
Country [27] 0 0
Spain
State/province [27] 0 0
Granada
Country [28] 0 0
Spain
State/province [28] 0 0
Madrid
Country [29] 0 0
Switzerland
State/province [29] 0 0
Aargau
Country [30] 0 0
Switzerland
State/province [30] 0 0
Vaud

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Pfizer
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Arvinas Estrogen Receptor, Inc.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to understand the safety and effects of the study medicine
ARV-471 (PF-07850327) given together with palbociclib in advanced breast cancer. In
particular, the study will compare the combination of ARV-471 plus palbociclib to standard of
care therapy (letrozole plus palbociclib). Both letrozole and palbociclib are medicines
already used for treatment of breast cancer. ARV-471 is a new medicine under study.

This study is seeking participants who have breast cancer that:

- Have a locally advanced or metastatic disease and cannot be fully cured by surgery or
radiation therapy. A metastatic disease is when disease has spread to other parts of the
body.

- Is sensitive to hormonal therapy such as tamoxifen. This is called estrogen receptor
positive disease.

- Have not received any prior medicine for advanced disease. Example medications include
tamoxifen or letrozole or exemestane.

The study will have an open-label SLI (study lead-in) before initiation of Phase 3 trial.
During SLI, two dose levels of palbociclib in combination with ARV-471 will be explored in
parallel. Assignment to the palbociclib dose is by chance. Half of the participant will
receive one dose and the other half another palbociclib dose. The purpose of SLI is to
determine the recommended Phase 3 dose of palbociclib to be administered in combination with
ARV-471.

In the Phase 3, half of the participants will take ARV-471 plus palbociclib while the other
half will take letrozole plus palbociclib. In both SLI and Phase 3, participants will take
the study medicines by mouth, with food, once a day. Participants will take the study
medicines until breast cancer increase in size or side effects become too severe. Side
effects refer to unwanted reactions to medications. Participants will visit the study clinic
about once every 4 weeks.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05909397
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Pfizer CT.gov Call Center
Address 0 0
Pfizer
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