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

NCT03206203 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: VICC BRE 15136NCI-2017-01150
• Study Type: interventional
• Target: 106
• Locations: 1 country
• Sites: 6

Brief 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 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

Conditions

Triple Negative Breast Cancer; Stage IV Breast Cancer; HER2 Negative; Invasive Breast Cancer

Outcome Measures

Primary Outcomes (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.

  Up to 3 years.

Secondary Outcomes (4)

• Overall Response Rate (ORR)

  Up to 3 years

• Clinical Benefit Rate (CBR)

  Up to 3 years

• Duration of Response (DOR)

  Up to 3 years

• Overall Survival (OS)

  Up to 3 years.

Other Outcomes (5)

• Changes in Gene Expression in Tumor Tissue as Assessed by Ribonucleic Acid-sequencing (RNA-seq)

  Baseline and upon disease progression, assessed for up to 3 years

• Assignment of a Triple Negative Subtype in Tumor Tissue as Assessed by Ribonucleic Acid-sequencing (RNA-seq)

  Baseline and upon disease progression, assessed for up to 3 years

• Define Mutations Present in the Tumors as Assessed by Ribonucleic Acid-sequencing (RNA-seq)

  Baseline and upon disease progression, assessed for up to 3 years

Study Arms (2)

Arm 1 (atezolizumab, carboplatin)

EXPERIMENTAL

Patients 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.

Drug: Atezolizumab; Drug: Carboplatin; Other: Laboratory Biomarker; Other: Quality-of-Life Assessment

Arm 2 (atezolizumab, carboplatin)

EXPERIMENTAL

Patients 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.

Drug: Atezolizumab; Drug: Carboplatin; Other: Laboratory Biomarker; Other: Quality-of-Life Assessment

Interventions

Atezolizumab DRUG

Given by vein

Arm 1 (atezolizumab, carboplatin); Arm 2 (atezolizumab, carboplatin)

Carboplatin DRUG

Given by vein

Arm 1 (atezolizumab, carboplatin); Arm 2 (atezolizumab, carboplatin)

Laboratory Biomarker OTHER

Correlative study

Arm 1 (atezolizumab, carboplatin); Arm 2 (atezolizumab, carboplatin)

Quality-of-Life Assessment OTHER

Ancillary studies

Arm 1 (atezolizumab, carboplatin); Arm 2 (atezolizumab, carboplatin)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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)
• 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

You may not qualify if:

• 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
• 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
• 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

Sponsors & Collaborators

• Vanderbilt-Ingram Cancer Center: lead
• National Cancer Institute (NCI): collaborator
• Genentech, Inc.: collaborator

Study Sites (6)

Georgetown University Lombardi Comprehensive Cancer Center

Washington D.C., District of Columbia, 20057, United States

Location

Indiana University Health Melvin Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Johns Hopkins University Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21231, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

Related Publications (1)

• 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.

  PMID: 38095878 DERIVED

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Breast Neoplasms

Interventions

atezolizumab; Carboplatin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals

Results Point of Contact

• Title: Teresa Melton
• Organization: Vanderbilt-Ingram Cancer Center

teresa.melton@vumc.org

615-936-7423

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 26, 2017
• First Posted: July 2, 2017
• Study Start: August 29, 2017
• Primary Completion: November 30, 2022
• Study Completion: October 4, 2023
• Last Updated: December 12, 2024
• Results First Posted: September 13, 2023

Record last verified: 2024-11

Locations

US (6)