Study of ASTX727 Plus Talazoparib in Patients With Triple Negative or Hormone Resistant/HER2-negative Metastatic Breast Cancer
NCT04134884
ABOUT THIS STUDY
FOR MORE INFORMATION
Contact a representative by phone, email, or visiting the study website. Please see the references below:
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317-278-5117
1. ≥ 18 years old at the time of informed consent
2. Ability to provide written informed consent and HIPAA authorization
3. Locally recurrent (not amenable to local therapy with curative intent) or metastatic breast cancer
1. Patients with triple negative breast cancer must have received at least one prior chemotherapy regimen for metastatic disease.
2. 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.
4. Measurable or evaluable disease based on RECIST 1.1 criteria.
5. Expansion Cohort only: Subjects must consent to undergo study specific biopsies and have disease amenable to biopsy.
a. 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.
6. Eastern Cooperative Oncology Group Performance Status 0 or 1
7. 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.
8. Adequate organ function as indicated by:
1. 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)
2. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 3.0 x ULN (= 1.5-3.0 x baseline if baseline is abnormal)
3. Calculated creatinine clearance of >/= 60 mL/min using the Cockcroft-Gault formula
4. Absolute neutrophil count (ANC) >/= 1.5 K/mm3
5. Platelets >/= 100 K/mm3
6. Hemoglobin (Hgb) >/= 9.0 g/dL
9. 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:
1. Has undergone a hysterectomy or bilateral oophorectomy; or
2. Has been naturally amenorrheic for at least 24 consecutive months.
10. 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).
1. Prior treatment with decitabine, guadecitabine or other known DNA Methyltransferase
inhibitors (DNMTis)
2. Prior treatment with talazoparib or other known PARPi (poly(ADP-ribose polymeras
inhibitor)
3. 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.
4. Active or symptomatic CNS disease
5. 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.
6. Patients with active malignancy other than breast cancer. Patients with prior
malignancies without recurrence after standard treatment will not be excluded
7. Chemotherapy within 3 weeks of registration
8. Radiation therapy within 2 weeks of registration
9. Hormone therapy within 2 weeks of registration
10. Patients requiring ongoing therapy with strong P-gp inhibitors
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Descriptive Information | |||||
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Brief Title ICMJE | Study of ASTX727 Plus Talazoparib in Patients With Triple Negative or Hormone Resistant/HER2-negative Metastatic Breast Cancer | ||||
Official Title ICMJE | 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 | ||||
Brief 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 | ||||
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 Type ICMJE | Interventional | ||||
Study Phase ICMJE | Phase 1 | ||||
Study Design ICMJE | Intervention Model: Sequential Assignment Intervention 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. Primary Purpose: Treatment | ||||
Condition ICMJE |
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Intervention ICMJE |
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Study Arms ICMJE | Experimental: ASTX727 + Talazoparib
Interventions:
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Publications * | Not Provided | ||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. | |||||
Recruitment Information | |||||
Recruitment Status ICMJE | Recruiting | ||||
Estimated Enrollment ICMJE | 32 | ||||
Original Estimated Enrollment ICMJE | Same as current | ||||
Estimated Study Completion Date ICMJE | July 1, 2022 | ||||
Estimated Primary Completion Date | December 31, 2021 (Final data collection date for primary outcome measure) | ||||
Eligibility Criteria ICMJE | Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||
Accepts Healthy Volunteers ICMJE | No | ||||
Contacts ICMJE |
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Listed Location Countries ICMJE | United States | ||||
Removed Location Countries | |||||
Administrative Information | |||||
NCT Number ICMJE | NCT04134884 | ||||
Other Study ID Numbers ICMJE | CTO-IUSCC-0684 | ||||
Has Data Monitoring Committee | Yes | ||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE | Not Provided | ||||
Responsible Party | Kathy Miller, Indiana University | ||||
Study Sponsor ICMJE | Kathy Miller | ||||
Collaborators ICMJE |
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Investigators ICMJE |
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PRS Account | Indiana University | ||||
Verification Date | December 2020 | ||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |