AzTrials
AzTrials

Breast CancerPhase 2TARANCT04690855

A Study to Evaluate TAlazoparib, Radiotherapy and Atezolizumab in gBRCA 1/2 Negative Patients With PD-L1+ Metastatic Triple Negative Breast Cancer

A Phase 2 study testing Talazoparib, Atezolizumab and Radiation in people with Breast Cancer and Triple Negative Breast Cancer, run by Mylin A. Torres, MD at 2 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

This is a Phase II study designed to assess efficacy and safety of talazoparib, high dose radiation, and atezolizumab in patients with metastatic TNBC that is PD-L1 positive. A total of 23 gBRCA pathogenic variant negative patients will be enrolled. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Breast Cancer, Triple Negative Breast Cancer
What is being tested?
Talazoparib, Atezolizumab and Radiation
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1 participants
Where
2 sitesUnited States
Study dates
4 Oct 2021to 20 Dec 2022
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Be willing and able to provide written informed consent/assent and HIPPA for the trial.
  • Ages 18-75 years old at time of consent. Female or male patients allowed.
  • ECOG PS of 0-2, KPS >/= 60%.
  • Biopsy proven metastatic triple negative breast cancer (estrogen receptor (</=10%), progesterone receptor (</=10%) and no overexpression of HER2 as evaluated by local institutions with at least 2 exracranial lesions of metastatic disease on imaging.
  • PD-L1 positive tumor infiltrate as defined as >/= 1% on IHC using the SP142 Ventana Assay.
  • Known gBRCA 1/2 status (gBRCA 1/2 negative [e.g. gBRCA wild-type, gBRCA variants of uncertain significance] are eligible).
Show all 23Show fewer
  • Patients must have at least 1 extracranial metastatic lesion (may be measurable or non-measurable disease by RECIST v 1.1) that is amenable to high dose radiotherapy and at least one additional extracranial lesion of measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST v1.1) that will not receive radiotherapy on this study. Of note, lesions maybe in the same organ but must be 2 cm apart and breast lesions may be treated.
  • Patients must have received at least one and no more than three previous lines of systemic treatment in the advanced setting with or without immune therapy. Patients with disease recurrence or progression following neoadjuvant or adjuvant cytotoxic chemotherapy are not eligible unless they have received at least one line of chemotherapy with or without immune therapy in the advanced setting. NOTE: Targeted small molecules (e.g. tyrosine kinase inhibitors), hormonal agents and monoclonal antibodies that inhibit angiogenesis (e.g. bevacizumab, afilbercept) are not counted in the number of lines of therapy. Cytotoxic chemotherapy with or without immune therapy for advanced disease prior to protocol treatment is not permitted within 2 weeks of the protocol treatment. Patients may or may not have received radiotherapy or neoadjuvant or adjuvant chemotherapy in the treatment of their initial, non-metastatic breast cancer, but must be entered on study 2 weeks after their last dose of radiotherapy, last cycle of chemotherapy and biologic therapy (if applicable) for mTNBC and have sufficient resolution of side effects per physician assessment at time of talazoparib.
  • Demonstrate adequate organ function as defined in the table below. All screening labs to be obtained within 14 days prior to registration.
  • Absolute neutrophil count > 1500/mcL
  • Platelets >/= 100,000 mm
  • Anemia >/= 9.0 g/dL (NOTE: The use of transfusion or other intervention to achieve Hgb >/= 9.0g/dl is acceptable)
  • Serum creatinine ≤ 1.5 × upper limit of normal (ULN) or calculated creatinine clearance ≥ 60 mL/min using Cockcroft-Gault equation for patients with creatinine levels > 1.5× institutional ULN
  • Total bilirubin ≤ 1.5× ULN OR direct bilirubin ≤ 1× ULN
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5× ULN unless liver metastases are present, in which case they must be ≤ 5×ULN
  • International normalized ratio (INR) or prothrombin time (PT) ≤1.5× ULN unless patient is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants
  • Activated partial thromboplastin time (aPTT) ≤ 1.5× ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
  • Patients must be eligible for radiotherapy, talazoparib, and atezolizumab.
  • Females of childbearing potential must have a negative serum or urine pregnancy test within 14 days prior to Cycle 1 Day 1. If a urine test is done and it is positive or cannot be confirmed as negative, a serum pregnancy test will be required. NOTE: Females are considered of child bearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months.
  • Women of childbearing potential and males must agree to use two effective methods of contraception or complete abstinence, from the time of signing the informed consent (females) or first day of study treatment (males), during the course of the study and for 7 months (females) and for 4 months (males) after the last dose of study drug.
  • Patients must not have active wound healing issues from surgery and sufficient resolution of surgical side effects, per physician assessment, at time of radiotherapy.
  • During participation on this study, no other investigation or commercial agents or therapy for cancer other than bisphosphonate, rank ligand inhibitors, atezolizumab, radiotherapy and talazoparib should be administered. NOTE: Patients may have received bisphosphonates or rank ligand inhibitors prior to and while on enrollment on study.
  • Patients must have the psychological ability and general health that permits completion of the study requirements and required follow up.

Who cannot join

  • gBRCA1/2 pathogenic variant positive
  • Four or more lines of cytotoxic chemotherapy for mTNBC.
  • Previous radiation to the metastases to be treated with radiation on this protocol.
  • Previous PARPi treatment (e.g. talazoparib, niraparib, olazaparib).
  • Progression of breast cancer within the first 3 months of prior immune therapy for non-metastatic or metastatic breast cancer.
  • Untreated CNS disease (patients with stable CNS disease for at least 28 days and asymptomatic treated CNS metastases are permitted).
Show all 18Show fewer
  • History of leptomeningeal disease.
  • History of autoimmune disease that has required systemic treatment (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  • Use of systemic glucocorticoid or immunosuppressive medications at time of enrollment.
  • Severe, active co-morbidity such as CHF or unstable angina within last 6 months, transmural MI within the last 6 months.
  • Acute bacterial or fungal infection requiring IV antibiotics at time of registration.
  • COPD or other respiratory illness requiring hospitalization at time of registration.
  • HIV positive with CD4 count <200 cells/ microliter.
  • Current hormone replacement therapy use.
  • Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy. Indolent cancers (such as low risk prostate or in-situ cancers) that are not being treated, are acceptable.
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • Receipt of the last dose or treatment of anti-cancer chemotherapy, radiotherapy, surgery, endocrine therapy, targeted therapy, biologic therapy, or tumor embolization ≤ 2 weeks (4 weeks for any monoclonal Antibody (mAb), 6 weeks for nitrosoureas or mitomycin C) prior to first dose of study treatment, or has not recovered (i.e., to ≤Grade 1 or Baseline) from clinically significant adverse events (AEs) due to these previously administered agents.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Winship Cancer Institute of Emory University

    Atlanta, Georgia, 30322

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35294

Other trials in United States

About this study

Official title: A Multi-institutional Phase II Study to Evaluate Efficacy and Safety of TAlazoparib, Radiotherapy and Atezolizumab in gBRCA 1/2 Negative Patients With PD-L1+ Metastatic Triple Negative Breast Cancer

This is a Phase II study designed to assess efficacy and safety of talazoparib, high dose radiation, and atezolizumab in patients with metastatic TNBC that is PD-L1 positive. A total of 23 gBRCA pathogenic variant negative patients will be enrolled. All patients will be treated with induction talazoparib of 1mg PO daily starting Day 1. Patients will then receive 8 Gy x 3 fractions to 2-4 metastatic lesions beginning Day 12,13, or 14 and given QOD. 840 mg of atezolizumab will be given intravenously (IV) on Day 15 of the 1st cycle and then on Day 1 and Day 15 of the remaining cycles. The sequence of administration is not specified on the days in which talazoparib and atezolizumab are given on the same day. Each cycle equals 28 days. Treatment will continue until progression or severe toxicity.

A safety lead in of up to 6 patients will be performed. Immune-related and non-immune related adverse events will be tracked up to 12 weeks post initiation of atezolizumab, as the majority of treatment-related toxicities from talazoparib, radiation, and atezolizumab occur within this time period.

Being tested
Talazoparib, Atezolizumab, Radiation
Medical subject headings
Breast Neoplasms, Triple Negative Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TalazoparibDrug

    Also called Talzenna

    Talazoparib 1 mg Orally Day 1 to Day 28

  • AtezolizumabDrug

    Also called Tecentriq

    Atezolizumab 840 mg IV over 60 minutes Day 15 of Cycle 1 then Day 1 and Day 15 of subsequent Cycles

  • RadiationRadiation

    Radiation 8 Gy will be given in 3 fractions QOD beginning Day 12, 13 or 14 of Cycle 1 but 24-72 hours prior to 1st dose of Atezolizumab

Study groups in NCT04690855
Study groupRoleWhat they receive
Study Treatment ArmExperimentalAll patients will be treated with induction talazoparib of 1mg PO daily starting Day 1. Patients will then receive 8 Gy x 3 fractions to 1-4 metastatic lesions beginning Day 12,13, or 14 and given QOD. 840 mg of atezolizumab will be given intravenously (IV) on Day 15 of the 1st cycle and then on Day 1 and Day 15 of the remaining cycles. The sequence of administration is not specified on the days in which talazoparib and atezolizumab are given on the same day. Each cycle equals 28 days. Treatment will continue until progression or severe toxicity. A safety lead in of up to 6 patients will be performed. Immune-related and non-immune related adverse events will be tracked up to 12 weeks post initiation of atezolizumab, as the majority of treatment-related toxicities from talazoparib, radiation, and atezolizumab occur within this time period.
Receives: Drug: Talazoparib; Drug: Atezolizumab; Radiation: Radiation

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective Response Rate (ORR) by RECIST 1.1

    Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) >= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD.

    ORR is defined as the proportion of all subjects with confirmed PR or CR according to RECIST 1.1, from the start of treatment until disease progression/recurrence

    Measured: Up to a maximum of 5 months

Secondary outcomes (8)

  1. Assess Adverse Events

    The frequency and severity of all treatment related adverse events for the single enrolled subject are reported by CTCAE v5 term and grade.

    Measured: Up to a maximum of 12 months.

  2. Progression Free Survival (PFS)

    Progression free survival (PFS) is defined as the day of study treatment initiation until disease progression by RECIST 1.1 or death whichever occurs first.

    Measured: Time of treatment start until the criteria for disease progression or death, up to a maximum of 5 months.

  3. Overall Survival (OS)

    Overall survival is defined as the time from treatment start until death or date of last contact.

    Measured: Time of treatment start until death, up to a maximum of 12 months.

  4. ORR by Immune-related RECIST (irRECIST)

    Per Immune-Related RECIST (irRECIST): Complete Response(irCR), Disappearance of all measurable and non-measurable lesions; Partial Response (irPR) >=30% decrease in tumor burden relative to baseline; Progressive Disease (irPD), >= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions confirmed by a consecutive assessment at least 4 week after first documentation; Stable Disease (irSD), not meeting criteria for irCR or irPR, in absence of irPD ORR is defined as the proportion of all subjects with CR and PR determined as per irRECIST

    Measured: Up to a maximum of 5 months

  5. Duration of Overall Response (DOR)

    DOR is defined as the time from the measurement criteria are met for complete or partial response (whichever status is recorded first) until the date of recurrent or disease progression.

    Measured: Up to a maximum of 5 months

  6. Disease Control Rate (DCR)

    Disease control rate (DCR) is defined as the percentage of patients with advanced or metastatic cancer who have achieved complete response, partial response and stable disease.

    Measured: Up to a maximum of 5 months

  7. Time to Progression (TTP)

    Time to progression (TTP) is defined as the day of study treatment initiation until disease progression by RECIST 1.1.

    Measured: Up to a maximum of 5 months

  8. Best Overall Tumor Response

    Best overall tumor response is defined as the best response recorded from the start of the study treatment until disease progression/recurrence.

    Measured: Time of treatment start until the criteria for disease progression, up to a maximum of 5 months.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Dec 2020
  2. Study start4 Oct 2021
  3. Primary completion18 Feb 2022
  4. Study completion20 Dec 2022

Why it stopped: This study has been terminated due to Lack of Accrual.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
1 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04690855
Sponsor's protocol ID
HCRN BRE19-433
Acronym
TARA
Status last verified
Nov 2023
First submitted
28 Dec 2020
Last updated
4 Dec 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Talazoparib, Atezolizumab and Radiation in people with Breast Cancer and Triple Negative Breast Cancer, run by Mylin A. Torres, MD at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 4 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 4 Dec 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response Rate (ORR) by RECIST 1.1 (time frame: Up to a maximum of 5 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04690855.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Dec 2023.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in