Clinical Trials /

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

NCT04134884

Description:

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

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: CTO-IUSCC-0684
  • NCT ID: NCT04134884

Conditions

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

Interventions

DrugSynonymsArms
TalazoparibASTX727 + Talazoparib
ASTX727ASTX727 + Talazoparib

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
ASTX727 + TalazoparibExperimental
  • Talazoparib
  • ASTX727

Eligibility Criteria

        Inclusion Criteria:

          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).

        Exclusion Criteria:

          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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

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
Safety Issue:
Description:rate of dose limiting toxicity will be assessed during cycle 1 (28 days) in patients enrolled during the dose escalation phase

Secondary Outcome Measures

Measure:Overall response rate
Time Frame:through study completion (i.e. up to 1 year)
Safety Issue:
Description:
Measure:Clinical benefit response for triple negative disease subjects
Time Frame:18 weeks
Safety Issue:
Description:clinical benefit response defined as complete response, partial response, or stable disease
Measure:Clinical benefit response for hormone receptor positive/ HER2 negative subjects
Time Frame:24 weeks
Safety Issue:
Description:clinical benefit response defined as complete response, partial response, or stable disease
Measure:Progression free survival in all enrolled subjects
Time Frame:through study completion (i.e. up to 1 year)
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Kathy Miller

Trial Keywords

  • Breast Cancer
  • Phase 1

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