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Triple Negative Breast CancerPhase 2NCT03206203

Carboplatin With or Without Atezolizumab in Treating Patients With Stage IV Triple Negative Breast Cancer

A Phase 2 study testing Atezolizumab, Carboplatin and Laboratory Biomarker in people with Triple Negative Breast Cancer and Stage IV Breast Cancer, run by Vanderbilt-Ingram Cancer Center at 6 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This randomized phase II trial studies how well carboplatin with or without atezolizumab works in treating patients with stage IV triple negative breast cancer. Drugs used in chemotherapy, such as carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Atezolizumab, Carboplatin and Laboratory Biomarker
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
106 participants
Where
6 sitesUnited States
Study dates
29 Aug 2017to 4 Oct 2023
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

  • Patients must provide informed written consent
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Clinical stage IV ER, PR, HER2 negative invasive mammary carcinoma, previously documented by histological analysis and that meets the following criteria:
  • HER2 negativity is defined as any of the following by local laboratory assessment: In-situ hybridization (ISH) non-amplified (ratio of HER2 to CEP17 < 2.0 or single probe average HER2 gene copy number < 4 signals/cell), or IHC 0 or IHC 1+ (if more than one test result is available and not all results meet the inclusion criterion definition, all results should be discussed with the protocol chair to establish eligibility of the patient)
  • ER and PR negativity are defined as =< 5% of cells expressing hormonal receptors via IHC analysis
  • Willing to undergo biopsy of a metastatic lesion (in patients with reasonably accessible metastatic lesions such as chest wall, skin, subcutaneous tissue, lymph nodes, bones, peripheral lung, and liver metastases)
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  • Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension by RECIST criteria version (v)1.1
  • Zero or one prior chemotherapy regimens for metastatic disease
  • No prior treatment with carboplatin
  • Absolute neutrophil count (ANC) >= 1500/mm^3 (without granulocyte colony-stimulating factor [G-CSF] support within 2 weeks prior to cycle 1, day 1)
  • Lymphocyte count >= 500/uL
  • Platelet count >= 100,000/mm^3 (without transfusion within 2 weeks prior to cycle 1, day 1)
  • Hemoglobin >= 9.0 g/dL
  • Patients may be transfused or receive erythropoietic treatment to meet this criterion
  • Calculated creatinine clearance >= 30 mL/min using the Calvert Formula
  • Bilirubin =< 2.5 x upper limits of normal if no liver metastases present; serum total bilirubin must be =< 3 x upper limits of normal for patients with Gilbert disease; total bilirubin =< 5 x upper limits of normal if liver metastases present
  • Serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT) =< 2.5 x upper limits of normal if no liver metastases present; SGOT, SGPT =< 5 x upper limits of normal if liver metastases present
  • Alkaline phosphatase =< 2.5 x upper limits of normal if no liver metastases present; alkaline phosphatase =< 5 x upper limits of normal if liver metastases present
  • For patients who are not postmenopausal (women) or surgically sterile (absence of ovaries and/or uterus or vasectomy), agreement to remain abstinent or to use two adequate methods of contraception (e.g., condoms, diaphragm, vasectomy/vasectomized partner, tubal ligation), during the treatment period and for at least 30 days after the last dose of study treatment; hormone based oral contraceptives are not allowed on study; postmenopausal is defined as:
  • Age >= 60 years
  • Age =< 60 years and amenorrheic for 12 months in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression; or follicle stimulating hormone and estradiol in the postmenopausal range
  • Subjects must complete all baseline screening assessments

Who cannot join

  • CANCER-SPECIFIC EXCLUSION CRITERIA
  • Spinal cord compression not definitively treated with surgery and/or radiation, or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for > 2 weeks prior to randomization
  • Known central nervous system (CNS) disease, except for treated asymptomatic CNS metastases, provided all of the following criteria are met: measurable disease outside the CNS, only supratentorial metastases allowed (i.e., no metastases to midbrain, pons, medulla, or spinal cord), no evidence of progression or hemorrhage after completion of CNS-directed therapy, no ongoing requirement for dexamethasone as therapy for CNS disease (anticonvulsants at a stable dose are allowed), no stereotactic radiation within 7 days or whole-brain radiation within 14 days prior to randomization
  • Leptomeningeal disease
  • Uncontrolled tumor-related pain: patients requiring narcotic pain medication must be on a stable regimen at registration; symptomatic lesions (e.g., bone metastases or metastases causing nerve impingement) amenable to palliative radiotherapy should be treated prior to randomization; patients should be recovered from the effects of radiation; there is no required minimum recovery period; asymptomatic metastatic lesions whose further growth would likely cause functional deficits or intractable pain (e.g., epidural metastasis that is not presently associated with spinal cord compression) should be considered for loco-regional therapy if appropriate prior to randomization
  • Uncontrolled hypercalcemia (> 1.5 mmol/L ionized calcium or calcium > 12 mg/dL or corrected serum calcium > upper limit of normal [ULN]) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy; patients who are receiving denosumab must discontinue denosumab use and replace it with a bisphosphonate instead while on study; patients receiving a bisphosphonate for skeletal metastases are not excluded and can continue treatment
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  • Malignancies other than triple negative breast cancer (TNBC) within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix or basal or squamous cell skin cancer)
  • Concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, hormonal therapy, biological therapy) other than the ones specified in the protocol; any other investigational drugs should be discontinued 2 weeks prior to the first dose of study medication
  • GENERAL MEDICAL EXCLUSION CRITERIA
  • Women only: pregnancy or lactation
  • Evidence of significant uncontrolled concomitant disease that in the opinion of the investigator could affect compliance with the protocol or interpretation of results, including significant liver disease (such as cirrhosis, uncontrolled major seizure disorder, or superior vena cava syndrome)
  • Significant cardiovascular disease, such as New York Heart Association (NYHA) cardiac disease (class II or greater), myocardial infarction within 3 months prior to randomization, unstable arrhythmias, or unstable angina; patients with a known left ventricular ejection fraction (LVEF) < 40% will be excluded; patients with known coronary artery disease, congestive heart failure not meeting the above criteria, or LVEF < 50% must be on a stable medical regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist if appropriate
  • Severe infection requiring systemic treatment within 4 weeks prior to randomization, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
  • Major surgical procedure within 4 weeks prior to randomization or anticipation of the need for a major surgical procedure during the course of the study other than for diagnosis; placement of central venous access catheter(s) (e.g., port or similar) is not considered a major surgical procedure and is therefore permitted
  • History of severe reactions (e.g. allergic, anaphylactic, or other hypersensitivity) to chimeric or humanized antibodies or fusion proteins
  • Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation
  • History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's syndrome, Guillain-Barre syndrome, multiple sclerosis, vasculitis, or glomerulonephritis; patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone are eligible for this study; patients with controlled type 1 diabetes mellitus on a stable insulin regimen are eligible for this study
  • Prior allogeneic stem cell or solid organ transplantation
  • History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest computed tomography (CT) scan; history of radiation pneumonitis in the radiation field (fibrosis) is permitted
  • Positive test for human immunodeficiency virus (HIV) (testing required prior to registration)
  • Active hepatitis B (defined as having a positive hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C
  • Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as having a negative hepatitis B surface antigen [HBsAg] test and a positive antibody to hepatitis B core antigen [anti-HBc] antibody test) are eligible
  • Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA
  • Active tuberculosis
  • Receipt of a live, attenuated vaccine within 4 weeks prior to initiation of study drug (cycle 1, day 1 [C1D1]) or anticipation that such a live, attenuated vaccine will be required during the study
  • Prior treatment with CD137 agonists, anti-PD-1, or anti-PD-L1 therapeutic antibody or pathway-targeting agents
  • Treatment with systemic immunostimulatory agents (including but not limited to interferons or IL-2) within 4 weeks or five half-lives of the drug (whichever is shorter) prior to randomization
  • Treatment with systemic corticosteroids or other systemic immunosuppressant medications (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [TNF] agents) within 2 weeks prior to cycle 1, day 1, or anticipated requirement for systemic immunosuppressive medications during the trial; patients who have received acute, low-dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea) may be enrolled in the study; patients with a history of allergic reaction to IV contrast requiring steroid pre-treatment should have baseline and subsequent tumor assessments performed using magnetic resonance imaging (MRI); the use of inhaled corticosteroids for chronic obstructive pulmonary disease, mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension, and low-dose supplemental corticosteroids for adrenocortical insufficiency are allowed
  • Psychiatric illness/social situations that would compromise patient safety or limit compliance with study requirements

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites

  • Johns Hopkins University Sidney Kimmel Comprehensive Cancer Center

    Baltimore, Maryland, 21231

  • University of North Carolina at Chapel Hill

    Chapel Hill, North Carolina, 27599

  • Indiana University Health Melvin Bren Simon Cancer Center

    Indianapolis, Indiana, 46202

  • Vanderbilt-Ingram Cancer Center

    Nashville, Tennessee, 37232

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Georgetown University Lombardi Comprehensive Cancer Center

    Washington D.C., District of Columbia, 20057

Other trials in United States

About this study

Official title: A Phase II Trial of Atezolizumab (Anti-PDL1) With Carboplatin in Patients With Metastatic Triple Negative Breast Cancer

This randomized phase II trial studies how well carboplatin with or without atezolizumab works in treating patients with stage IV triple negative breast cancer. Drugs used in chemotherapy, such as carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as atezolizumab, may interfere with the ability of tumor cells to grow and spread. Giving carboplatin with atezolizumab may work better in treating patients with stage IV triple negative breast cancer

Read the detailed description

Primary objective:

To evaluate the efficacy, as measured by progression free survival (PFS) of carboplatin + atezolizumab (using irRECIST) versus carboplatin alone (using RECIST) in patients with triple negative metastatic breast cancer

Secondary objectives:

  • To determine overall response rate.
  • To evaluate the efficacy, as measured by clinical benefit rate, of carboplatin + atezolizumab (using irRECIST) versus carboplatin (using RECIST) alone in patients with triple negative metastatic breast cancer. Clinical benefit rate is defined as complete response plus partial response plus stable disease for 6 months.
  • To determine the duration of response for patients achieving a partial or complete response.
  • To evaluate the overall survival (OS) of carboplatin + atezolizumab versus carboplatin alone in patients with triple negative metastatic breast cancer.

TERTIARY OBJECTIVES:

  • To perform the following correlative studies from biopsies taken at baseline:
  1. Tumor infiltrating lymphocyte frequency and phenotype (TILs) at baseline
  2. PD-L1 expression from the baseline pre-treatment tissue and at progression lesion, performed by IHC (SP142 clone)
  3. HER2 (IHC, FISH) and ER/PR levels (IHC) from a metastatic site
  4. Perform RNA-seq to determine non-synonymous mutation burden in expressed genes and gene expression to assign a triple negative subtype at baseline for correlations with clinic outcome
  5. Immune phenotyping (IHC) for markers of T cell subsets and activation (CD4, CD8, FoxP3, CD25, Glut1) and exhaustion (PD1, CTLA4) and test feasibility of flow cytometric analyses to include additional markers
  • To assess the effect of BRCA mutations on response to the study drugs
  • To evaluate the effect of steroids on the efficacy of atezolizumab To assess the prognostic effects of TILs on PFS and CBR in patients receiving atezolizumab
Being tested
Atezolizumab, Carboplatin, Laboratory Biomarker, Quality-of-Life Assessment
Medical subject headings
Triple Negative Breast Neoplasms, Breast Neoplasms

What participants receive

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

  • AtezolizumabDrug

    Given by vein

  • CarboplatinDrug

    Given by vein

  • Laboratory BiomarkerOther

    Correlative study

  • Quality-of-Life AssessmentOther

    Ancillary studies

Study groups in NCT03206203
Study groupRoleWhat they receive
Arm 1 (atezolizumab, carboplatin)ExperimentalPatients receive atezolizumab IV over 30-60 minutes and carboplatin IV on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Atezolizumab; Drug: Carboplatin; Other: Laboratory Biomarker; Other: Quality-of-Life Assessment
Arm 2 (atezolizumab, carboplatin)ExperimentalPatients receive carboplatin as in Arm 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients may cross-over to Arm 1 upon disease progression.
Receives: Drug: Atezolizumab; Drug: Carboplatin; Other: Laboratory Biomarker; Other: Quality-of-Life Assessment

What is being measured

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

  1. Progression Free Survival (PFS)

    The PFS is defined as the time from the first day of treatment to the first observation of disease progression (RECIST V1.1) or death of any cause. Those without events were censored at the last follow up. The median PFS time will be estimated using the Kaplan-Meier method with 95% confidence intervals.

    Measured: Up to 3 years.

Secondary outcomes (4)

  1. Overall Response Rate (ORR)

    Patient response to treatment was evaluated by RECIST V1.1. The ORR (CR + PR) and corresponding 95% confidence intervals (exact) were estimated among evaluable patients.

    Measured: Up to 3 years

  2. Clinical Benefit Rate (CBR)

    Patient response to treatment was evaluated by RECIST 1.1. The CBR (CR + PR+stable disease ≥ 6 months) and corresponding 95% confidence intervals (exact) were estimated among evaluable patients.

    Measured: Up to 3 years

  3. Duration of Response (DOR)

    DOR was defined as the time from CR or PR to progression using RECIST V1.1. The median DOR and corresponding 95% confidence intervals was estimated uisng Kaplan-Meier method.

    Measured: Up to 3 years

  4. Overall Survival (OS)

    OS is defined as the time from first day of treatment to death. Those alive were censored at the last follow up. The median and OS time and corresponding 95% confidence intervals were estimated using Kaplan-meier method.

    Measured: Up to 3 years.

Timeline

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

  1. First posted2 Jul 2017
  2. Study start29 Aug 2017
  3. Primary completion30 Nov 2022
  4. Study completion4 Oct 2023

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
Randomised
Intervention model
Crossover
Masking
None (open label)
Enrolment
106 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03206203
Sponsor's protocol ID
VICC BRE 15136
Other IDs
NCI-2017-01150
Status last verified
Nov 2024
First submitted
26 Jun 2017
Last updated
12 Dec 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Lehmann BD, Abramson VG, Dees EC, Shah PD, Ballinger TJ, Isaacs C, Santa-Maria CA, An H, Gonzalez-Ericsson PI, Sanders ME, Newsom KC, Abramson RG, Sheng Q, Hsu CY, Shyr Y, Wolff AC, Pietenpol JA. Atezolizumab in Combination With Carboplatin and Survival Outcomes in Patients With Metastatic Triple-Negative Breast Cancer: The TBCRC 043 Phase 2 Randomized Clinical Trial. JAMA Oncol. 2024 Feb 1;10(2):193-201. doi: 10.1001/jamaoncol.2023.5424.

    PubMed 38095878

  • Taylor BC, Sun X, Gonzalez-Ericsson PI, Sanchez V, Sanders ME, Wescott EC, Opalenik SR, Hanna A, Chou ST, Van Kaer L, Gomez H, Isaacs C, Ballinger TJ, Santa-Maria CA, Shah PD, Dees EC, Lehmann BD, Abramson VG, Pietenpol JA, Balko JM. NKG2A Is a Therapeutic Vulnerability in Immunotherapy Resistant MHC-I Heterogeneous Triple-Negative Breast Cancer. Cancer Discov. 2024 Feb 8;14(2):290-307. doi: 10.1158/2159-8290.CD-23-0519.

    PubMed 37791898

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Atezolizumab, Carboplatin and Laboratory Biomarker in people with Triple Negative Breast Cancer and Stage IV Breast Cancer, run by Vanderbilt-Ingram Cancer Center at 6 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 22 inclusion and 29 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: finished, as of the sponsor's last update on 12 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 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 13 Sep 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?

Progression Free Survival (PFS) (time frame: Up to 3 years.). 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 NCT03206203, which also lists 2 linked publications.

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 12 Dec 2024.

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