Metastatic Breast CancerPhase 1NCT04134884
Study of ASTX727 Plus Talazoparib in Patients With Triple Negative or Hormone Resistant/HER2-negative Metastatic Breast Cancer
A Phase 1 study testing Talazoparib and ASTX727 in people with Metastatic Breast Cancer and Triple Negative Breast Cancer, run by Kathy Miller at 2 sites in United States.
Trial summary
This is a Phase I study to test the safety of a combination of ASTX727 with talazoparib in patients with triple negative breast cancer or hormone resistant/HER2-negative metastatic breast cancer Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Breast Cancer, Triple Negative Breast Cancer, Hormone Receptor Positive Tumor
- What is being tested?
- Talazoparib and ASTX727
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 2 sitesUnited States
- Study dates
- 1 Apr 2020to 14 Mar 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ≥ 18 years old at the time of informed consent
- Ability to provide written informed consent and HIPAA authorization
- Locally recurrent (not amenable to local therapy with curative intent) or metastatic breast cancer
- Patients with triple negative breast cancer must have received at least one prior chemotherapy regimen for metastatic disease.
- Patients with hormone-positive, HER2-negative disease must have received treatment with and progressed on at least one prior endocrine therapy including a CDK4/6 inhibitor in the metastatic setting.
- Measurable or evaluable disease based on RECIST 1.1 criteria.
Show all 21Show fewer
- Only subjects who have disease amenable to biopsy will be asked to consent to serial tumor biopsies. Consent for biopsy is not required for participation.
- NOTE: If no amendable disease is present at the time of biopsy, subjects may continue participation in the study and further study specific biopsies will not be required.
- Eastern Cooperative Oncology Group Performance Status 0 or 1
- Patients with treated, asymptomatic central nervous system (CNS) disease may participate if the patient is > 4 weeks from completion of CNS therapy (radiation and/or surgery), is clinically stable at the time of study entry, and is receiving a stable or decreasing dose of corticosteroid therapy. Brain MRI or head CT is required at screening for patients with known brain metastases.
- Adequate organ function as indicated by:
- Total bilirubin </= ULN (upper limit of normal) (except in patients with documented Gilbert's disease, who must have a total bilirubin </= 3.0 mg/dL)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) </= 3.0 x ULN (</= 1.5-3.0 x baseline if baseline is abnormal)
- Calculated creatinine clearance of >/= 60 mL/min using the Cockcroft-Gault formula
- Absolute neutrophil count (ANC) >/= 1.5 K/mm3
- Platelets >/= 100 K/mm3
- Hemoglobin (Hgb) >/= 9.0 g/dL
- Women of childbearing potential must have a negative pregnancy test within 14 days of protocol registration. Women are considered to have childbearing potential (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) unless they meet one of the following criteria:
- Has undergone a hysterectomy or bilateral oophorectomy; or
- Has been naturally amenorrheic for at least 24 consecutive months.
- Women of childbearing potential and men must agree to use effective contraception throughout the study and for 7 months after the last study treatment. Note: Acceptable methods of birth control include abstinence, partner with previous vasectomy, placement of an intrauterine device (IUD), condom with spermicidal foam/gel/film/cream/suppository, diaphragm or cervical vault cap, or hormonal birth control (pills or injections).
Who cannot join
- Prior treatment with decitabine, guadecitabine or other known DNA Methyltransferase inhibitors (DNMTis)
- Prior treatment with talazoparib or other known PARPi (poly(ADP-ribose polymeras inhibitor)
- Known deleterious breast cancer susceptibility gene (BRCA) mutation. Patients with BRCA variants of unknown significance (VUS) or who have not had germline genetic testing may participate.
- Active or symptomatic CNS disease
- Patients with HER2+ disease
- HER2 will be considered positive if scored 3+ by immunohistochemistry (IHC) or 2+ by IHC associated with a fluorescence in situ hybridization (FISH) ratio of > 2.0 or > 6 total HER2 gene copies per cell.
Show all 11Show fewer
- Patients with active malignancy other than breast cancer. Patients with prior malignancies without recurrence after standard treatment will not be excluded
- Chemotherapy within 3 weeks of registration
- Radiation therapy within 2 weeks of registration
- Hormone therapy within 2 weeks of registration
- Patients requiring ongoing therapy with strong P-gp inhibitors
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Indiana University Melvin & Bren Simon Cancer Center
Indianapolis, Indiana, 46202
Wake Forest Baptist Comprehensive Cancer Center
Winston-Salem, North Carolina, 27157
About this study
Official title: A Phase I Study of ASTX727 Plus Talazoparib in Patients With Triple Negative or Hormone Resistant/ Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Metastatic Breast Cancer
This is a Phase I study to test the safety of a combination of ASTX727 with talazoparib in patients with triple negative breast cancer or hormone resistant/HER2-negative metastatic breast cancer
Read the detailed description
The phase I portion will use a traditional 3 + 3 design and standard definitions of DLT based on toxicity experienced during the first cycle of therapy. Patients with triple negative breast cancer (TNBC) and hormone resistant/HER2 negative (HRBC) metastatic disease will be enrolled and analyzed together during the dose escalation cohorts. Once the maximum tolerated dose is determined, we will enroll a small expansion cohort to further characterize safety and provide preliminary efficacy estimates.The expansion cohort will be limited to 14 patients; 7 with TNBC and 7 with HRBC. The dose level selected for expansion will be based on the totality of the data available including toxicity during the DLT evaluation period, toxicity during subsequent cycles, and correlative results.
- Being tested
- Talazoparib, ASTX727
- Keywords
- Breast Cancer, Phase 1
- Medical subject headings
- Breast Neoplasms, Triple Negative Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TalazoparibDrug
Talazoparib will be taken on days 4-21, 6-21 or 1-21 at a dose level of 0.25, 0.5, 0.75 or 1.0 mg depending on cohort assignment
ASTX727Drug
ASTX727 will be taken on days 1 and 3, days 1,3,5 or days 1 through 5 of the 28 day cycle at doses of 10 mg:100 mg or 15 mg:100 mg depending on cohort assignment
| Study group | Role | What they receive |
|---|---|---|
| ASTX727 + Talazoparib | Experimental | Not described Receives: Drug: Talazoparib; Drug: ASTX727 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety of ASTX727 plus talazoparib using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v 5.0
Measured: through study completion i.e up to 1 year
Rate of dose limiting toxicity
rate of dose limiting toxicity will be assessed during cycle 1 (28 days) in patients enrolled during the dose escalation phase
Measured: 28 days
Secondary outcomes (4)
Overall response rate
Measured: through study completion (i.e. up to 1 year)
Clinical benefit response for triple negative disease subjects
clinical benefit response defined as complete response, partial response, or stable disease
Measured: 18 weeks
Clinical benefit response for hormone receptor positive/ HER2 negative subjects
clinical benefit response defined as complete response, partial response, or stable disease
Measured: 24 weeks
Progression free survival in all enrolled subjects
Measured: through study completion (i.e. up to 1 year)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2019
- Study start1 Apr 2020
- Primary completion30 Jan 2024
- Study completion14 Mar 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Breast CancerStudies of the same condition, open and under way.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Model description
- The dose escalation phase will begin by enrolling 3 patients to the cohort 1 dose level. Patients will be observed for 28 days or one cycle of therapy for dose limiting toxicity (DLT). If 0 of 3 patients experience a DLT, the study will proceed to cohort 2. If 1 patient experiences a DLT, 3 additional patients will be enrolled into cohort 1. If 1 of 6 patients experience a DLT, the study will proceed to the cohort 2 dose level. If \> 2/3 or 2/6 patients in cohort 1 experience DLT, we will de-escalate to cohort -1. Identical DLT evaluation and dose escalation/de-escalation decision rules will be used in subsequent cohorts. A total of 6 patients will be treated at the highest dose level achieved to ensure that 6 patients have been treated at the proposed maximum tolerated dose before proceeding to the expansion cohorts.
- Masking
- None (open label)
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kathy Miller
- Sponsor type
- University, hospital or other
- Collaborators
- Pfizer, Astex Pharmaceuticals, Inc., Van Andel Institute Stand Up to Cancer Team
- Responsible party
- Sponsor-investigator, Kathy Miller, Indiana University
- Investigators
- Kathy Miller, MD, Principal investigator, Indiana University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04134884
- Sponsor's protocol ID
- CTO-IUSCC-0684
- Status last verified
- Mar 2024
- First submitted
- 18 Oct 2019
- Last updated
- 22 Mar 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of ASTX727 Plus Talazoparib in Patients With Triple Negative or Hormone Resistant/ Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Metastatic Breast Cancer
- ClinicalTrials.gov ID
- NCT04134884
- Acronym / sponsor ID
- CTO-IUSCC-0684
- Keywords
- Breast Cancer, Phase 1
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- Kathy MillerUniversity, hospital or other
- Collaborators
- Pfizer, Astex Pharmaceuticals, Inc., Van Andel Institute Stand Up to Cancer Team
- Study start
- 1 Apr 2020 (actual)
- Primary completion
- 30 Jan 2024 (actual)
- Study completion
- 14 Mar 2024 (actual)
- First posted
- 22 Oct 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase I study to test the safety of a combination of ASTX727 with talazoparib in patients with triple negative breast cancer or hormone resistant/HER2-negative metastatic breast cancer
Detailed description
The phase I portion will use a traditional 3 + 3 design and standard definitions of DLT based on toxicity experienced during the first cycle of therapy. Patients with triple negative breast cancer (TNBC) and hormone resistant/HER2 negative (HRBC) metastatic disease will be enrolled and analyzed together during the dose escalation cohorts. Once the maximum tolerated dose is determined, we will enroll a small expansion cohort to further characterize safety and provide preliminary efficacy estimates.The expansion cohort will be limited to 14 patients; 7 with TNBC and 7 with HRBC. The dose level selected for expansion will be based on the totality of the data available including toxicity during the DLT evaluation period, toxicity during subsequent cycles, and correlative results.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- The dose escalation phase will begin by enrolling 3 patients to the cohort 1 dose level. Patients will be observed for 28 days or one cycle of therapy for dose limiting toxicity (DLT). If 0 of 3 patients experience a DLT, the study will proceed to cohort 2. If 1 patient experiences a DLT, 3 additional patients will be enrolled into cohort 1. If 1 of 6 patients experience a DLT, the study will proceed to the cohort 2 dose level. If > 2/3 or 2/6 patients in cohort 1 experience DLT, we will de-escalate to cohort -1. Identical DLT evaluation and dose escalation/de-escalation decision rules will be used in subsequent cohorts. A total of 6 patients will be treated at the highest dose level achieved to ensure that 6 patients have been treated at the proposed maximum tolerated dose before proceeding to the expansion cohorts.
| Arm | Type | Receives |
|---|---|---|
| ASTX727 + Talazoparib | Experimental | Drug: Talazoparib, Drug: ASTX727 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- ≥ 18 years old at the time of informed consent
- Ability to provide written informed consent and HIPAA authorization
- Locally recurrent (not amenable to local therapy with curative intent) or metastatic breast cancer
- Measurable or evaluable disease based on RECIST 1.1 criteria.
- Only subjects who have disease amenable to biopsy will be asked to consent to serial tumor biopsies. Consent for biopsy is not required for participation.
Key exclusion criteria (11 listed)
- Prior treatment with decitabine, guadecitabine or other known DNA Methyltransferase inhibitors (DNMTis)
- Prior treatment with talazoparib or other known PARPi (poly(ADP-ribose polymeras inhibitor)
- Known deleterious breast cancer susceptibility gene (BRCA) mutation. Patients with BRCA variants of unknown significance (VUS) or who have not had germline genetic testing may participate.
- Active or symptomatic CNS disease
- Patients with HER2+ disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TalazoparibTalazoparib will be taken on days 4-21, 6-21 or 1-21 at a dose level of 0.25, 0.5, 0.75 or 1.0 mg depending on cohort assignment | Drug | ASTX727 + Talazoparib |
| ASTX727ASTX727 will be taken on days 1 and 3, days 1,3,5 or days 1 through 5 of the 28 day cycle at doses of 10 mg:100 mg or 15 mg:100 mg depending on cohort assignment | Drug | ASTX727 + Talazoparib |
Primary outcome
Safety of ASTX727 plus talazoparib using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v 5.0
Time frame: through study completion i.e up to 1 year
Rate of dose limiting toxicity
Time frame: 28 days
rate of dose limiting toxicity will be assessed during cycle 1 (28 days) in patients enrolled during the dose escalation phase
4 secondary outcomes
Overall response rate
Time frame: through study completion (i.e. up to 1 year)
Clinical benefit response for triple negative disease subjects
Time frame: 18 weeks
Clinical benefit response for hormone receptor positive/ HER2 negative subjects
Time frame: 24 weeks
Progression free survival in all enrolled subjects
Time frame: through study completion (i.e. up to 1 year)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Mar 2024.
Related trials for Metastatic Breast Cancer
RecruitingPhase 2
Gene Signatures to Guide HR+MBC Therapy in a Diverse Cohort
Invasive Mammary Carcinoma, Metastatic Breast Cancer
Not yet recruiting
Augmented-Reality ICG Fluorescence Second-Look for Residual Nodal Disease After Axillary Dissection in Breast Cancer
Breast Cancer, Breast Neoplasms
RecruitingPhase 2
BrAin Metastasis in tripLe Negateive Breast Cancer: IvoneScimab and Trop2 ADC
Triple-Negative Breast Cancer (TNBC), Brain Metastases
RecruitingPhase 1/2
A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Metastatic or Locally Advanced Breast Cancer
Metastatic Breast Cancer
RecruitingObservational study
Collection of CSF Samples From Participants With Metastatic Triple Negative Breast Cancer (TNBC) and HER2+ Breast Cancer With no Prior History Nor Active Radiographically Detectable Brain Metastases
Breast Cancer, Breast Carcinoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kathy Miller, MD principal investigator
Indiana University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Talazoparib and ASTX727 in people with Metastatic Breast Cancer and Triple Negative Breast Cancer, run by Kathy Miller at 2 sites in United States.
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 21 inclusion and 11 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: finished, as of the sponsor's last update on 22 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Safety of ASTX727 plus talazoparib using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v 5.0 (time frame: through study completion i.e up to 1 year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 22 Mar 2024; AzTrials last refreshed its copy on 7 Nov 2026.