Clinical Trials /

Study to Evaluate Sacituzumab Govitecan in Combination With Talazoparib in Patients With Metastatic Breast Cancer.

NCT04039230

Description:

This research is studying the effect of Antibody-Drug Conjugate Sacituzumab Govitecan in Combination with the Poly (Adenosine Diphosphate [ADP]-Ribose) Polymerase (PARP) Inhibitor Talazoparib in Patients with Metastatic Triple-Negative Breast Cancer.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study to Evaluate Sacituzumab Govitecan in Combination With Talazoparib in Patients With Metastatic Breast Cancer.
  • Official Title: Phase 1b/2 Study to Evaluate Antibody-Drug Conjugate Sacituzumab Govitecan in Combination With PARP Inhibitor Talazoparib in Patients With Metastatic Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: 19-239
  • NCT ID: NCT04039230

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
TalazoparibSacituzumab Govitecan+Talazoparib
Sacituzumab GovitecanSacituzumab Govitecan+Talazoparib

Purpose

This research is studying the effect of Antibody-Drug Conjugate Sacituzumab Govitecan in Combination with the Poly (Adenosine Diphosphate [ADP]-Ribose) Polymerase (PARP) Inhibitor Talazoparib in Patients with Metastatic Triple-Negative Breast Cancer.

Detailed Description

      This is a Phase I/II clinical trial. You are being asked to participate in the Phase I
      portion of the study. A Phase I clinical trial tests the safety of an investigational drug
      and also tries to define the appropriate dose of the investigational drug to use for further
      studies. "Investigational" means that the drug is being studied.

      The U.S. Food and Drug Administration (FDA) has not approved sacituzumab govitecan as a
      treatment for any disease.

      The FDA has not approved talazoparib for this specific disease, but it has been approved for
      other uses in breast cancer.

      Sacituzumab govitecan is an antibody-drug conjugate which means it's made up of an antibody
      attached to an anticancer drug. An antibody is a protein normally made by the immune system
      (the system in the body that fights off diseases). Sacituzumab govitecan is believed to work
      by binding the antibody portion of the drug to the tumor(s) while the anticancer drug portion
      works to prevent the cancer cells from growing/spreading.

      Talazoparib belongs to a group of drugs called PARP inhibitors. PARP is a protein that is
      involved with repairing damaged DNA (the genetic material of cells). Talazoparib is believed
      to work by inhibiting (stopping) the PARP proteins from working in the cancer cells so that
      the cancer cannot fix its damaged DNA.

      The investigators believe that the combination of sacituzumab govitecan and talazoparib may
      help stop the cancer from growing and spreading by administering an anticancer drug directly
      to the cancerous tumor(s) through sacituzumab govitecan and by stopping the cancer's cells
      from fixing its damaged DNA through talazoparib.
    

Trial Arms

NameTypeDescriptionInterventions
Sacituzumab Govitecan+TalazoparibExperimentalSacituzumab Govitecan is administered on days 1 and 8 of a 21 day cycle. Talazoparib is administered daily
  • Talazoparib
  • Sacituzumab Govitecan

Eligibility Criteria

        Inclusion Criteria:

          -  Adult (≥ 18 years of age).

          -  Histologically confirmed stage IV (metastatic) breast cancer.

          -  Participants must have biopsy proven ER negative (ER-), PR negative (PR-), HER2
             negative, invasive breast cancer, by AJCC 7th edition staging. ER, PR, and HER2
             positivity would be determined per institutional (local) guidelines.

          -  Previously treated with no more than one prior therapeutic regimens for metastatic
             disease during dose-expansion (no limit on prior therapeutic regimens in
             dose-escalation). In patients with disease recurrence within 12 months of
             (neo)adjuvant therapy, the (neo)adjuvant therapy would count as one prior regimen for
             this criterion. Radiation therapy or local therapy/surgery would not count as prior
             regimen for this criterion.

          -  Pre- and postmenopausal women are eligible.

          -  ECOG performance status = 0-1

          -  Measurable disease as per RECIST Version 1.1.

          -  Ability to understand and the willingness to sign a written informed consent document.
             Patient has signed the Informed Consent (ICF) prior to any screening procedures being
             performed and is able to comply with protocol requirements.

          -  At least 2 weeks beyond treatment (chemotherapy, targeted therapy, immunotherapy,
             and/or radiation therapy) or major surgery and recovered from all acute toxicities
             (adverse events from prior anti-cancer agents need to be grade 1 or lower; grade 2
             alopecia or peripheral neuropathy is permitted).

          -  At least 2 weeks beyond corticosteroids (however, low dose corticosteroids <20 mg
             prednisone or equivalent daily are permitted).

          -  Patient has adequate bone marrow and organ function as defined by the following
             laboratory values at screening:

               -  Absolute neutrophil count ≥1.5 × 109/L

               -  Platelets ≥100 × 109/L

               -  Hemoglobin ≥10.0 g/dL

               -  INR ≤1.5

               -  creatinine clearance ≥60 mL/min

               -  In the absence of liver metastases, alanine aminotransferase (ALT) and aspartate
                  aminotransferase (AST) <2.5 x ULN. If the patient has liver metastases, ALT and
                  AST <5 x ULN

          -  Total bilirubin ≤3.0 x ULN or direct bilirubin ≤1.5 x ULN in patients with
             well-documented Gilbert's Syndrome.

               -  Fasting plasma glucose <140 mg/dL / 7.7 mmol/L and Glycosylated Hemoglobin
                  (HbA1c) ≤ 8% (both criteria must be met).

        Exclusion Criteria:

          -  Participants who have had anti-cancer therapy including targeted therapy or
             chemotherapy or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C)
             prior to entering the study, or those who have not recovered from adverse events
             (clinically significant grade 2 or higher adverse events; grade 2 alopecia or
             peripheral neuropathy is permitted) due to prior anti-cancer agents.

          -  Participants who have received prior PARP inhibitor (allowed in phase 1b), and/or
             sacituzumab govitecan. Participants who have received prior irinotecan or ADC backbone
             with SN-38 or topoisomerase-1 inhibitor.

          -  Participants with progressive CNS metastatic disease. Patients with stable CNS
             metastasis would be eligible, provided mets radiologically stable for at least one
             month, and patient is not actively taking steroids (more than 20 mg of prednisone or
             equivalent dose).

          -  Current use of strong CYP3A inhibitors/inducers, or P-gp inhibitors within 7 days
             prior to randomization. For a list of strong CYP3A inhibitors/inducers and P-gp
             inhibitors, refer to Appendix C.

          -  Uncontrolled inter-current illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements. Patient has impairment of gastrointestinal (GI) function or GI
             disease that may significantly alter the absorption of the study drugs (e.g.,
             ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome,
             or small bowel resection).

          -  Clinically significant, uncontrolled heart disease and/or cardiac repolarization
             abnormality including any of the following:

               -  History of angina pectoris, symptomatic pericarditis, coronary artery bypass
                  graft (CABG) or myocardial infarction within 6 months prior to study entry.

               -  Documented cardiomyopathy.

               -  History of cardiac failure, significant/symptomatic bradycardia, Long QT
                  syndrome, family history of idiopathic sudden death or congenital long QT
                  syndrome or any of the following:

               -  Known risk to prolong the QT interval or induce Torsade's de Pointes.

               -  Uncorrected hypomagnesemia or hypokalemia.

               -  Systolic Blood Pressure (SBP) >160 mmHg or <90 mmHg.

               -  Bradycardia (heart rate <50 at rest), by ECG or pulse.

               -  On screening, inability to determine the QTcF interval on the ECG (i.e.:
                  unreadable or not interpretable) or QTcF >450 screening ECG.

          -  HIV-positive participants on combination antiretroviral therapy are ineligible. These
             participants are at increased risk of lethal infections when treated with
             marrow-suppressive therapy. Appropriate studies will be undertaken in participants
             receiving combination antiretroviral therapy when indicated.

          -  Pregnant women are excluded from this study because the safety of study medications is
             not established in pregnant women.

          -  Women of child-bearing potential, defined as all women physiologically capable of
             becoming pregnant, or fertile men, unless they are using highly effective methods of
             contraception throughout the study and after study drug discontinuation (till 8 weeks
             in women and six months in males, post-study). Male patient should not donate sperm
             while on treatment and up to 6 months after last dose. Women are considered
             post-menopausal and not of child bearing potential if they have had 12 months of
             natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age
             appropriate, history of vasomotor symptoms) or have had surgical bilateral
             oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago.
             In the case of oophorectomy alone, only when the reproductive status of the woman has
             been confirmed by follow up hormone level assessment is she considered not of child
             bearing potential. Highly effective contraception methods include:

               -  Total abstinence when this is in line with the preferred and usual lifestyle of
                  the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal,
                  post-ovulation methods) and withdrawal are not acceptable methods of
                  contraception.

               -  Female sterilization (have had surgical bilateral oophorectomy with or without
                  hysterectomy), total hysterectomy, or tubal ligation at least six weeks before
                  taking study treatment. In case of oophorectomy alone, only when the reproductive
                  status of the woman has been confirmed by follow up hormone level assessment

               -  Use of oral, injected or implanted hormonal methods of contraception or placement
                  of an intrauterine device (IUD) or intrauterine system (IUS), or other forms of
                  hormonal contraception that have comparable efficacy (failure rate <1%), for
                  example hormone vaginal ring or transdermal hormone contraception.

               -  In case of use of oral contraception, women should have been stable on the same
                  pill for a minimum of 3 months before taking study treatment. Note: While oral
                  contraceptives are allowed, they should be used in conjunction with a barrier
                  method of contraception due to unknown effect of drug-drug interaction.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose Limiting Toxicity
Time Frame:2 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Time-to-Tumor Response
Time Frame:2 years
Safety Issue:
Description:
Measure:Duration of response
Time Frame:2 years
Safety Issue:
Description:
Measure:Progression-Free Survival
Time Frame:2 Years
Safety Issue:
Description:
Measure:Overall Survival Rate
Time Frame:2 years
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Massachusetts General Hospital

Trial Keywords

  • Breast Cancer

Last Updated