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

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NCT04134884

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Study Location
Wake Forest Baptist Comprehensive Cancer Center
Winston-Salem, North Carolina, 27157, United States
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Contact
317-278-5117
[email protected]
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Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Metastatic Breast Cancer, Triple Negative Breast Cancer, Hormone Receptor Positive Tumor
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
18 + years
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

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
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


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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Metastatic Breast Cancer, Triple Negative Breast Cancer, Hormone Receptor Positive TumorStudy of ASTX727 Plus Talazoparib in Patients With Triple Negative or Hormone Resistant/HER2-negative Metastatic Breast Cancer
NCT04134884
  1. Winston-Salem, North Carolina
  2. Indianapolis, Indiana
ALL GENDERS
18 Years+
years
MULTIPLE SITES
Advanced Information
Descriptive Information
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.

Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Metastatic Breast Cancer
  • Triple Negative Breast Cancer
  • Hormone Receptor Positive Tumor
Intervention  ICMJE
  • Drug: Talazoparib
    Talazoparib will be given orally once daily on a continuous basis, beginning on Day 1 of Cycle 1 at a dose level of 0.5, 0.75 or 1.0 mg depending on cohort assignment)
  • Drug: ASTX727
    ASTX727 will be given orally once daily on Days 1-5 of the 28 day cycle at doses of 20 mg:100 mg, 30 mg: 100 mg, and 35mg : 100 mg depending on cohort assignment
Study Arms  ICMJE Experimental: ASTX727 + Talazoparib
Interventions:
  • Drug: Talazoparib
  • Drug: ASTX727
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
 (submitted: October 18, 2019)		32
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 1, 2022
Estimated Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study:All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Jessica Sollars, RN317-278-5117[email protected]
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
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Kathy Miller, Indiana University
Study Sponsor  ICMJE Kathy Miller
Collaborators  ICMJE
  • Pfizer
  • Astex Pharmaceuticals, Inc.
  • Van Andel Institute Stand Up to Cancer Team
Investigators  ICMJE
Principal Investigator:Kathy Miller, MDIndiana University
PRS Account Indiana University
Verification Date April 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP