Study of ASTX727 Plus Talazoparib in Patients With Triple Negative or Hormone Resistant/HER2-negative Metastatic Breast Cancer

NCT04134884 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: CTO-IUSCC-0684
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 2

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

Conditions

Metastatic Breast Cancer; Triple Negative Breast Cancer; Hormone Receptor Positive Tumor

Keywords

Breast Cancer; Phase 1

Outcome Measures

Primary Outcomes (2)

• Safety of ASTX727 plus talazoparib using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v 5.0

  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

  28 days

Secondary Outcomes (4)

• Overall response rate

  through study completion (i.e. up to 1 year)

• Clinical benefit response for triple negative disease subjects

  18 weeks

• Clinical benefit response for hormone receptor positive/ HER2 negative subjects

  24 weeks

• Progression free survival in all enrolled subjects

  through study completion (i.e. up to 1 year)

Study Arms (1)

ASTX727 + Talazoparib

EXPERIMENTAL

Drug: Talazoparib; Drug: ASTX727

Interventions

Talazoparib DRUG

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

ASTX727 + Talazoparib

ASTX727 DRUG

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

ASTX727 + Talazoparib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 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.
• 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.
• 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.
• 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

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• Kathy Miller: lead
• Pfizer: collaborator
• Astex Pharmaceuticals, Inc.: collaborator
• Van Andel Institute Stand Up to Cancer Team: collaborator

Study Sites (2)

Indiana University Melvin & Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Wake Forest Baptist Comprehensive Cancer Center

Winston-Salem, North Carolina, 27157, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms

Interventions

talazoparib; decitabine and cedazuridine drug combination

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Kathy Miller, MD

  Indiana University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Ballvé-Lantero Professor of Medicine

Model Details: 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.

Study Record Dates

• First Submitted: October 18, 2019
• First Posted: October 22, 2019
• Study Start: April 1, 2020
• Primary Completion: January 30, 2024
• Study Completion: March 14, 2024
• Last Updated: March 22, 2024

Record last verified: 2024-03

Locations

US (2)