Clinical Trials /

TALAVE: Induction Talazoparib Followed by Combination of Talazoparib and Avelumab in Advanced Breast Cancer

NCT03964532

Description:

This is a multi-institutional pilot trial for patients with advanced breast cancer. The trial is designed to assess the safety and tolerability of induction talazoparib followed by combination of talazoparib and avelumab. As an exploratory endpoint, the study team will evaluate the immunomodulatory effects of induction talazoparib followed by the combination of talazoparib and avelumab in patients with advanced breast cancer.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: TALAVE: Induction Talazoparib Followed by Combination of Talazoparib and Avelumab in Advanced Breast Cancer
  • Official Title: TALAVE: A Pilot Trial of Induction Talazoparib Followed by Combination of Talazoparib and Avelumab in Advanced Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: STUDY00000023
  • NCT ID: NCT03964532

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
TalazoparibTalzennaPhase I/Phase II
AvelumabBavencioPhase I/Phase II

Purpose

This is a multi-institutional pilot trial for patients with advanced breast cancer. The trial is designed to assess the safety and tolerability of induction talazoparib followed by combination of talazoparib and avelumab. As an exploratory endpoint, the study team will evaluate the immunomodulatory effects of induction talazoparib followed by the combination of talazoparib and avelumab in patients with advanced breast cancer.

Trial Arms

NameTypeDescriptionInterventions
Phase I/Phase IIExperimentalTalazoparib (1mg by mouth [PO] daily D1-28) will be provided as monotherapy for the first cycle. Starting with cycle 2 and for all subsequent cycles, treatment with avelumab (800 mg intravenously [IV] D1 every 2 weeks) will be added to talazoparib.
  • Talazoparib
  • Avelumab

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically confirmed advanced breast cancer not amenable to curative treatment by
             surgery or radiotherapy, that is amenable to biopsy

          -  Radiographically measurable disease by RECIST v1.1

          -  Age ≥ 18 years

          -  Life expectancy of more than 3 months

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1

          -  Signed informed consent form

          -  Patients with a standard 12-lead electrocardiogram (ECG) with the following parameters
             at screening (defined as the mean of the triplicate ECGs):

               1. QTc interval at screening < 481 msec

               2. Resting heart rate 50-100bpm

          -  Adequate hepatic, bone marrow, and renal function at the time of enrollment:

               1. Bone Marrow: Absolute neutrophil count (ANC) ≥ 1,500/mm3; Platelets ≥
                  100,000/mm3; Hemoglobin ≥ 9.0 g/dL. Patients must be able to meet the criteria
                  without transfusion or receipt of colony stimulating factors within 2 weeks
                  before obtaining sample

               2. Creatinine clearance ≥ 60 mL/min based on Cockcroft-Gault equation

               3. Hepatic function: aspartate aminotransferase (AST) and alanine aminotransferase
                  (ALT) ≤ 2.5 × the upper normal limit of institution's normal range. Total
                  bilirubin ≤ 1.5 × the upper normal limit of institution's normal range. For
                  subjects with liver metastases, AST and ALT < 5 × the upper normal limit of
                  institution's normal range, and total bilirubin >1.5 - 3.0 x the upper normal
                  limit of institution's normal range are acceptable as long as there is no
                  persistent nausea, vomiting, right upper quadrant pain or tenderness, fever,
                  rash, or eosinophilia

               4. Prothrombin Time (PT) and Partial Thromboplastin Time (PTT) must be ≤ 2 X the
                  upper limit of the institution's normal range and International Normalized Ratio
                  (INR) < 2. Subjects on anticoagulation (such as coumadin) will be permitted to
                  enroll as long as the INR is in the acceptable therapeutic range as determined by
                  the investigator

          -  Patients may have received an unlimited number of prior therapies. The last dose of
             systemic therapy must have occurred a minimum of 2 weeks prior to C1D1.

          -  Patients must have fully recovered from all effects of surgery. Patients must have had
             at least two weeks after minor surgery and four weeks after major surgery before
             starting therapy. Minor procedures requiring conscious sedation such as endoscopies or
             mediport placement may only require a 24-hour waiting period, but this must be
             discussed with an investigator

          -  Women of childbearing potential must have a negative serum pregnancy test within 14
             days prior to initiation of treatment and/or postmenopausal women must be amenorrheic
             for at least 12 months to be considered of non-childbearing potential

          -  Patient is capable of swallowing pills whole

          -  Subject, or legally authorized representative (LAR) is capable of understanding and
             complying with parameters as outlined in the protocol and able to sign and date the
             informed consent, approved by the IRB, prior to the initiation of any screening or
             study-specific procedures

          -  Patient, or LAR, must consent to multiple biopsies during study.

        Exclusion Criteria:

          -  Prior disease progression while receiving anti-PD-1 or anti-PD-L1 therapy within 6
             months of use

          -  Prior exposure to PARP inhibitor-based therapy

          -  Patients with known untreated central nervous system (CNS) metastases

          -  Recent severe infection or antibiotic use, or known chronic infection with human
             immunodeficiency virus (HIV) or hepatitis B virus

          -  Signs or symptoms of infection within 2 weeks prior to Cycle 1, Day 1

          -  Diagnosis of immunodeficiency or is receiving systemic steroid or other
             immunosuppressive therapy

          -  Active autoimmune disease that has required systemic treatment in the past 2 years

          -  History of tuberculosis

          -  History of allogenic bone marrow transplant or solid organ transplant

          -  History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced),
             organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing
             pneumonia, etc.), or evidence of active pneumonitis on screening chest CT scan

          -  Life-threatening visceral disease or other severe concurrent disease that would, in
             the investigator's judgment, cause unacceptable safety risks, contraindicate patient
             participation in the clinical study or compromise compliance with the protocol

          -  Live vaccine administration within 30 days of planned start of study therapy

          -  Cardiovascular disease problems including unstable angina, therapy for lifethreatening
             ventricular arrhythmia, or myocardial infarction, stroke within the last 6 months, or
             a diagnosis of congestive heart failure

          -  Patient has impairment of gastrointestinal (GI) function or GI disease that may
             significantly alter the absorption of the study drugs

          -  Presence of a psychiatric illness or social situation that would limit compliance with
             study requirements

          -  Women who are pregnant or breastfeeding

          -  Patients with history of another active malignancy within the past 2 years, excluding
             non-melanoma carcinoma of the skin

          -  Patients receiving any other investigational agents

          -  Patients must not have had radiotherapy encompassing >20% of the bone marrow

          -  Patients must not have current evidence of any condition, therapy, or laboratory
             abnormality (including active or uncontrolled myelosuppression [ie, anemia,
             leukopenia, neutropenia, thrombocytopenia]) that might confound the results of the
             study or interfere with the patient's participation for the full duration of the study
             treatment or that makes it not in the best interest of the patient to participate

          -  Patients must not be considered a poor medical risk due to a serious, uncontrolled
             medical disorder, nonmalignant systemic disease, or active, uncontrolled infection.

          -  Current use of potent P-gp inhibitors within 7 days prior to randomization. For a list
             of potent P-gp inhibitors
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:The number of participants with treatment-related adverse events as assessed by CTCAE v4.0.
Time Frame:28 Days
Safety Issue:
Description:Toxicity analysis will be conducted in all patients receiving at least one dose of talazoparib.

Secondary Outcome Measures

Measure:The anti-tumor efficacy as measured by Overall Response Rate (ORR).
Time Frame:4 Months
Safety Issue:
Description:The distributions of OS will be estimated using the Kaplan-Meier method.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Georgetown University

Trial Keywords

  • Breast Cancer
  • Advanced Breast Cancer
  • Talazoparib
  • Avelumab

Last Updated

February 1, 2021