Recurrent Breast Inflammatory CarcinomaPhase 2NCT03202316
Atezolizumab, Cobimetinib, and Eribulin in Treating Patients With Chemotherapy Resistant Metastatic Inflammatory Breast Cancer
A Phase 2 study testing Atezolizumab, Cobimetinib and Eribulin in people with Recurrent Breast Inflammatory Carcinoma and Stage IV Breast Inflammatory Carcinoma, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
This phase II trial studies how well atezolizumab, cobimetinib, and eribulin work in treating patients with inflammatory breast cancer that has spread to other places in the body (metastatic). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Recurrent Breast Inflammatory Carcinoma, Stage IV Breast Inflammatory Carcinoma
- What is being tested?
- Atezolizumab, Cobimetinib and Eribulin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 37 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Aug 2017to 31 Dec 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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
- Signed informed consent form (ICF) and comply with the requirements of the study protocol
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- Confirmed diagnosis of inflammatory breast cancer according to international consensus criteria: (1) onset: rapid onset of breast erythema, edema, and/or peau d'orange, and/or warm breast, with or without an underlying breast mass (2) duration: history of such findings no more than 6 months (3) extent: erythema occupying at least 1/3 of whole breast (4) pathology: pathologic confirmation of invasive carcinoma
- Patients with recurrent or metastatic IBC after standard systemic therapy are eligible; patients who have disease progression while receiving standard anthracycline or taxane based neoadjuvant therapy are also eligible. a. patients with HER2-positive disease must have had at least 2 lines of anti-HER2 therapy, including Perjeta and Kadcyla; b. prior eribulin treatment is allowed
- At least one metastatic lesion amendable for biopsy (core, punch, or fine needle aspiration [FNA]); if the patient only has lymph nodes, these are considered amenable but will not be biopsied
- At least one site of measurable disease (per Response Evaluation Criteria in Solid Tumors [RECIST] 1.1), local or distant
Show all 20Show fewer
- Any estrogen receptor (ER), progesterone receptor (PR), HER2 status
- Absolute neutrophil count (ANC) >= 1500 cells/uL (obtained within 14 days prior to the first study treatment [PD window day 1])
- White blood cell (WBC) counts > 2500/uL (obtained within 14 days prior to the first study treatment [PD window, day 1])
- Lymphocyte count >= 300/uL (obtained within 14 days prior to the first study treatment [PD window day 1])
- Platelet count >= 100,000/uL (obtained within 14 days prior to the first study treatment [PD window day 1])
- Hemoglobin >= 9.0 g/dL (obtained within 14 days prior to the first study treatment [PD window day 1])
- Total bilirubin =< 1.5 x upper limit of normal (ULN) with the following the exception: Patients with known Gilbert disease who have serum bilirubin level =< 3 x ULN may be enrolled (obtained within 14 days prior to the first study treatment [PD window, day 1])
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN with the exception: Patients with liver involvement: AST and/or ALT =< 5 x ULN (obtained within 14 days prior to the first study treatment [PD window, day 1])
- Alkaline phosphatase =< 2.5 x ULN with the exception: Patients with documented liver involvement or bone metastases: alkaline phosphatase =< 5 x ULN (obtained within 14 days prior to the first study treatment [PD window, day 1])
- Serum creatinine =< 1.5 x ULN or creatinine clearance >= 50 mL/min on the basis of the Cockcroft-Gault glomerular filtration rate estimation (obtained within 14 days prior to the first study treatment [PD window, day 1])
- For women of childbearing potential or male subjects: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of < 1% per year, during the treatment period and for at least 5 months after the last dose of treatment
- International normalized ratio (INR) and activated partial thromboplastin time (aPTT) =< 1.5 x ULN for patients who do not receive therapeutic anticoagulation
- Patients receiving therapeutic anticoagulation (such as low-molecular-weight heparin or warfarin) should be on a stable dose
- Left ventricular ejection fraction >= 50% measured by multigated acquisition (MUGA) scan or echocardiogram
Who cannot join
- Any approved anticancer therapy for treatment purpose is not allowed, or need to be stopped at least 2 weeks prior to initiation of study treatment; however, the following are allowed: a. endocrine therapy (selective estrogen receptor modulator [SERM], aromatase inhibitor, fulvestrant) b. palliative radiotherapy for bone metastases > 1 week prior to study treatment c. stable brain metastasis and asymptomatic treated central nervous system (CNS) metastases are allowed, patient must show stable disease by CNS radiographic study >= 4 weeks from completion of radiotherapy and >= 2 weeks from discontinuation of corticosteroids
- Adverse events (AEs) from prior anticancer therapy that have not resolved to grade =< 1 except for alopecia and neuropathy
- Grade 3 or above neuropathy induced from prior treatment, that is not resolved to grade 2 or below despite best supportive care
- Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease
- Pregnancy, lactation, or breastfeeding
- Known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
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- Inability to comply with study and follow-up procedures
- Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjogren's syndrome, Guillain-Barre syndrome, or multiple sclerosis, with the following exception: a. patients with a history of autoimmune hypothyroidism who are on thyroid replacement hormone are eligible for the study; b. patients with controlled type 1 diabetes mellitus who are on an insulin regimen are eligible for the study; c. patients with eczema, psoriasis, lichen simplex chronicus of vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided that they meet the following conditions are met: i. rash must cover < 10% of body surface area.; ii. disease is well controlled at baseline and requires only low-potency topical corticosteroids; iii. no occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high potency or oral corticosteroids within the previous 12 months
- Acute exacerbations of underlying condition within the last 12 months (requiring psoralen plus ultraviolet A radiation [PUVA], methotrexate, retinoids, biologic agents, oral calcineurin inhibitors; high potency or oral steroids)
- Known 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 computed tomography (CT) scan:
- History of radiation pneumonitis in the radiation field (fibrosis) is permitted
- Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications
- Known history of human immunodeficiency virus (HIV) infection or active hepatitis B (chronic or acute) or hepatitis C infection; but: a. patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for hepatitis C virus (HCV) RNA; b. patients with past or resolved hepatitis B infection (defined as having a negative hepatitis B surface antigen [HBsAg] test and a positive anti-HBc [antibody to hepatitis B core antigen] antibody test) are eligible, but should sample for hepatitis B virus (HBV) DNA and referral to virologist to monitor for HBV reactivation
- Active tuberculosis based on history, symptoms, physical exam, imaging
- Severe infections within 4 weeks prior to study treatment, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
- Signs or symptoms of infection within 2 weeks prior to study treatment
- Received oral or IV antibiotics within 2 weeks prior to study treatment
- Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible
- Major surgical procedure within 28 days prior to study treatment or anticipation of need for a major surgical procedure during the course of the study
- Patients must agree not to receive any live, attenuated influenza vaccine (e.g., FluMist) within 28 days prior to receiving study treatment, during treatment or within 5 months following the last dose of atezolizumab
- Malignancies other than the disease under study within 5 years prior to study treatment, with the exception of those with a negligible risk of metastasis or death and with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, or ductal carcinoma in situ treated surgically with curative intent) or undergoing active surveillance per standard-of-care management (e.g., chronic lymphocytic leukemia Rai Stage 0)
- COBIMETINIB-SPECIFIC EXCLUSION CRITERIA (ONLY FOR COHORT I):
- History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment/central serous chorioretinopathy (CSCR), retinal vein occlusion (RVO), or neovascular macular degeneration
- Patients will be excluded if they currently have the following risk factors for retinal vein occlusion (RVO): (1) uncontrolled glaucoma with intra-ocular pressures >= 21 mmHg (2) serum cholesterol >= grade 2 (3) hypertriglyceridemia >= grade 2 (4) hyperglycemia (fasting) >= grade 2
- Patients with congestive heart failure, congenital long QT syndrome; bradyarrhythmias, drugs known to prolong the QT interval unless the principal investigator and/or attending physician deems the risk for QT prolongation to be low
- The following foods/supplements are prohibited at least 7 days prior to initiation of and during study treatment: (1) St. John's wort or hyperforin (potent CYP3A4 enzyme inducer) (2) grapefruit juice (potent cytochrome P450 CYP3A4 enzyme inhibitor)
- ATEZOLIZUMAB-RELATED EXCLUSION CRITERIA:
- Prior treatment with anti-PD-1, or anti-PD-L1 therapeutic antibody or pathway targeting agents: (a) patients who have received prior treatment with anti·CTLA-4 may be enrolled, provided the following requirements are met: (i) minimum of 12 weeks from the first dose of anti-CTLA-4 and > 6 weeks from the last dose; (ii) no history of severe immune-related adverse effects from anti-CTLA 4 (National Cancer Institute [NCI] Common Terminology for Cancer Adverse Effects CTCAE] grade 3 and 4)
- Treatment with systemic immunostimulatory agents (including but not limited to interferon [IFN]-a or interleukin [IL]-2) within 6 weeks or five half-lives of the drug (whichever is shorter) prior to study treatment
- Treatment with investigational agent within 4 weeks prior to study treatment (or within five half lives of the investigational product, whichever is longer)
- Treatment with systemic immunosuppressive medications (including but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [anti-TNF] agents) within 2 weeks prior to study treatment; a. patients who have received acute, low dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea) may be enrolled; b. the use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed
- History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
- Patients with prior solid organ transplantation on anti-immunosuppressant
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase II Study of Triple Combination of Atezolizumab + Cobimetinib + Eribulin (ACE) or Atezolizumab + Eribulin (AE) in Patients With Recurrent/Metastatic Inflammatory Breast Cancer
This phase II trial studies how well atezolizumab, cobimetinib, and eribulin work in treating patients with inflammatory breast cancer that has spread to other places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Cobimetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as eribulin, 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. Giving atezolizumab, cobimetinib, and eribulin may work better in treating patients with inflammatory breast cancer.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine ORR (overall response rate) of metastatic inflammatory breast cancer (BC) (mIBC) patients treated with this proposed combinatorial atezolizumab, cobimetinib, and eribulin (ACE) therapy via phase II. (ACE, Cohort I) II. To determine ORR (overall response rate) for double combination of atezolizumab and eribulin (AE). (AE, cohort II)
SECONDARY OBJECTIVES:
- To further characterize the safety and tolerability of atezolizumab + cobimetinib + eribulin.
II. To further characterize the safety and tolerability of atezolizumab + eribulin.
III. To determine CBR (clinical benefit rate): (stable disease [SD] + complete response [CR] + partial response [PR] >= 24 weeks).
III. To determine the duration of response (DOR). IV. To determine progression free survival (PFS). V. To determine 2 years overall survival (OS).
EXPLORATORY OBJECTIVES:
- To determine the progressive disease (PD) biomarker changes induced by combinatorial therapy using liquid and tissue based assays to investigate microenvironment via multiplex imaging, proportional study of T cells: CD3, CD8 composition and change, macrophage (M1 and M2), PD-L1 expression on circulating tumor cell (CTC).
II. To determine the immune pathway related biomarker changes induced by combinatorial therapy via multiplex serum cytokine assays.
III. This translational biomarker assays will be done based on collaboration with plasma based ribonucleic acid (RNA) sequencing (RNA-seq) in collaboration with Lambowitz laboratory (lab) (University of Texas at Austin [UT Austin]), Oncomine next-generation sequencing (NGS) study on tumor/circulating tumor deoxyribonucleic acid (ctDNA) with Wistuba lab, and bioinformatics with Futreal lab.
OUTLINE:
COHORT I: Patients receive atezolizumab intravenously (IV) over about 30-60 minutes every 2 weeks, cobimetinib orally (PO) daily for 3 weeks on, 1 week off for 4 weeks of the safety lead-in course. Patients then receive atezolizumab IV over about 30-60 minutes every 2 weeks, cobimetinib PO daily for 3 weeks on, 1 week off, and eribulin IV over 2-5 minutes on days 1 and 8 of cycles 1-4. Cycles 1-4 repeat every 21 days and subsequent cycles with atezolizumab and cobimetinib repeat every 28 days in the absence of disease progression or unacceptable toxicity.
COHORT II: Patients receive atezolizumab IV over about 30-60 minutes every 3 weeks for cycles 1-6 and every 4 weeks for subsequent cycles, and eribulin IV over 2-5 minutes on days 1 and 8 of cycles 1-6. Cycles 1-6 repeat every 21 days and subsequent cycles with atezolizumab repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of the study treatment, patients are followed for 3 months and then every 6 months for 2 years.
- Being tested
- Atezolizumab, Cobimetinib, Eribulin, Laboratory Biomarker Analysis, Pharmacological Study
- Medical subject headings
- Inflammatory Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AtezolizumabDrug
Also called MPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A
Given IV
CobimetinibDrug
Also called Cotellic, GDC-0973, MEK Inhibitor GDC-0973, XL518
Given PO
EribulinDrug
Also called ER-086526
Given IV
Laboratory Biomarker AnalysisOther
Correlative studies
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Cohort I (atezolizumab, cobimetinib, eribulin) | Experimental | Patients receive atezolizumab IV over about 30-60 minutes every 2 weeks, cobimetinib PO daily for 3 weeks on, 1 week off for 4 weeks of the safety lead-in course. Patients then receive atezolizumab IV over about 30-60 minutes every 2 weeks, cobimetinib PO daily for 3 weeks on, 1 week off, and eribulin IV over 2-5 minutes on days 1 and 8 of cycles 1-4. Cycles 1-4 repeat every 21 days and subsequent cycles with atezolizumab and cobimetinib repeat every 28 days in the absence of disease progression or unacceptable toxicity. Receives: Drug: Atezolizumab; Drug: Cobimetinib; Drug: Eribulin; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study |
| Cohort II (atezolizumab, eribulin) | Experimental | Patients receive atezolizumab IV over about 30-60 minutes every 3 weeks for cycles 1-6 and every 4 weeks for subsequent cycles, and eribulin IV over 2-5 minutes on days 1 and 8 of cycles 1-6. Cycles 1-6 repeat every 21 days and subsequent cycles with atezolizumab repeat every 28 days in the absence of disease progression or unacceptable toxicity. Receives: Drug: Atezolizumab; Drug: Eribulin; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall response rate (ORR)
Calculated per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. ORR is defined as the rate of patients who achieved partial response or complete response as the best response. All tumor response will be evaluated by RECIST 1.1. The ORR will be estimated along with 95% confidence intervals. Logistic regression model will be used to assess other variables' effect on the best ORR.
Measured: Up to 2 years
Secondary outcomes (7)
Incidence of dose limiting toxicity (DLT) of cobimetinib and atezolizumab (safety lead-in)
Evaluated according to Common Terminology Criteria for Adverse Events version 4.0. DLT is defined as any treatment-emergent adverse events (AEs) occurring during the first 7 weeks (progressive disease window and cycle 1) not clearly attributable to a cause other than the study drugs.
Measured: Up to 7 weeks
Clinical benefit rate (CBR)
Defined as the rate of patients who achieved complete response, partial response, and stable disease for >= 24 weeks as the best response of treatment. CBR is defined as the rate of patients who achieved complete response, partial response, and stable disease for >= 24 weeks as the best response of treatment.
Measured: Up to 2 years
Duration of response (DOR)
Defined as the period measured from the date of the first occurrence of a complete response (CR) or partial response (PR) (whichever status is recorded first) until the first date that progressive disease or death is documented. Patients who have not progressed and who have not died by the date of data cutoff for analysis will be censored at the time of last tumor assessment date. If no tumor assessments were performed after the date of the first occurrence of a CR or PR, DOR will be censored at the date of the first occurrence of a CR or PR plus remaining stable response from that time point.
Measured: Up to 2 years
Progression free survival (PFS)
Data from patients who have not experienced disease progression or death will be censored at the last tumor assessment date and known to be free of disease progression. Data from patients with no post-baseline tumor assessment will be censored at the treatment start date plus 1 day. PFS will be estimated using the Kaplan-Meier method and the comparison between or among patient's characteristic groups will be evaluated by log-rank test. The Cox regression model may be applied to assess the effect of covariates of interest on PFS.
Measured: From date of treatment start until date of first documented disease progression or death, whichever occurs first, assessed up to 2 years
Overall survival (OS)
OS will be estimated using the Kaplan-Meier method and the comparison between or among patient's characteristic groups will be evaluated by log-rank test. The Cox regression model may be applied to assess the effect of covariates of interest on OS.
Measured: At 2 years
Pharmacodynamic markers
Biomarker changes induced by combinatorial therapy using liquid and tissue based assays to investigate microenvironment via multiplex imaging, proportional study of T cells: CD3, CD8 composition and change, macrophage (M1and M2), PD-L1 expression on circulating tumor cell will be measured. Immune pathway related biomarker changes induced by combinatorial therapy via multiplex serum cytokine assays will be determined. This translational biomarker assays will be done based on collaboration with plasma based ribonucleic acid (RNA) sequencing (RNA-seq) in collaboration with Lambowitz laboratory (lab), Oncomine next-generation sequencing (NGS) study on tumor/circulating tumor deoxyribonucleic acid (ctDNA) with Wistuba lab, and bioinformatics with Futreal lab.
Measured: Up to 2 years
Incidence of adverse events
Detailed safety and tolerability of the combination of cobimetinib, atezolizumab, and eribulin will be assessed. Toxicity data will be summarized by frequency tables.
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jun 2017
- Study start11 Aug 2017
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Recurrent Breast Inflammatory CarcinomaStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 37 participants (estimated)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Vicente Valero, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03202316
- Sponsor's protocol ID
- 2016-0890
- Other IDs
- NCI-2017-01601, 2016-0890
- Status last verified
- Jun 2026
- First submitted
- 27 Jun 2017
- Last updated
- 10 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Triple Combination of Atezolizumab + Cobimetinib + Eribulin (ACE) or Atezolizumab + Eribulin (AE) in Patients With Recurrent/Metastatic Inflammatory Breast Cancer
- ClinicalTrials.gov ID
- NCT03202316
- Acronym / sponsor ID
- 2016-0890
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 37 participants (estimated)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Study start
- 11 Aug 2017 (actual)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 28 Jun 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II trial studies how well atezolizumab, cobimetinib, and eribulin work in treating patients with inflammatory breast cancer that has spread to other places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Cobimetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as eribulin, 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. Giving atezolizumab, cobimetinib, and eribulin may work better in treating patients with inflammatory breast cancer.
Detailed description
PRIMARY OBJECTIVES:
- To determine ORR (overall response rate) of metastatic inflammatory breast cancer (BC) (mIBC) patients treated with this proposed combinatorial atezolizumab, cobimetinib, and eribulin (ACE) therapy via phase II. (ACE, Cohort I) II. To determine ORR (overall response rate) for double combination of atezolizumab and eribulin (AE). (AE, cohort II)
SECONDARY OBJECTIVES:
- To further characterize the safety and tolerability of atezolizumab + cobimetinib + eribulin.
II. To further characterize the safety and tolerability of atezolizumab + eribulin.
III. To determine CBR (clinical benefit rate): (stable disease [SD] + complete response [CR] + partial response [PR] >= 24 weeks).
III. To determine the duration of response (DOR). IV. To determine progression free survival (PFS). V. To determine 2 years overall survival (OS).
EXPLORATORY OBJECTIVES:
- To determine the progressive disease (PD) biomarker changes induced by combinatorial therapy using liquid and tissue based assays to investigate microenvironment via multiplex imaging, proportional study of T cells: CD3, CD8 composition and change, macrophage (M1 and M2), PD-L1 expression on circulating tumor cell (CTC).
II. To determine the immune pathway related biomarker changes induced by combinatorial therapy via multiplex serum cytokine assays.
III. This translational biomarker assays will be done based on collaboration with plasma based ribonucleic acid (RNA) sequencing (RNA-seq) in collaboration with Lambowitz laboratory (lab) (University of Texas at Austin [UT Austin]), Oncomine next-generation sequencing (NGS) study on tumor/circulating tumor deoxyribonucleic acid (ctDNA) with Wistuba lab, and bioinformatics with Futreal lab.
OUTLINE:
COHORT I: Patients receive atezolizumab intravenously (IV) over about 30-60 minutes every 2 weeks, cobimetinib orally (PO) daily for 3 weeks on, 1 week off for 4 weeks of the safety lead-in course. Patients then receive atezolizumab IV over about 30-60 minutes every 2 weeks, cobimetinib PO daily for 3 weeks on, 1 week off, and eribulin IV over 2-5 minutes on days 1 and 8 of cycles 1-4. Cycles 1-4 repeat every 21 days and subsequent cycles with atezolizumab and cobimetinib repeat every 28 days in the absence of disease progression or unacceptable toxicity.
COHORT II: Patients receive atezolizumab IV over about 30-60 minutes every 3 weeks for cycles 1-6 and every 4 weeks for subsequent cycles, and eribulin IV over 2-5 minutes on days 1 and 8 of cycles 1-6. Cycles 1-6 repeat every 21 days and subsequent cycles with atezolizumab repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of the study treatment, patients are followed for 3 months and then every 6 months for 2 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort I (atezolizumab, cobimetinib, eribulin) | Experimental | Drug: Atezolizumab, Drug: Cobimetinib, Drug: Eribulin, Other: Laboratory Biomarker Analysis, Other: Pharmacological StudyPatients receive atezolizumab IV over about 30-60 minutes every 2 weeks, cobimetinib PO daily for 3 weeks on, 1 week off for 4 weeks of the safety lead-in course. Patients then receive atezolizumab IV over about 30-60 minutes every 2 weeks, cobimetinib PO daily for 3 weeks on, 1 week off, and eribulin IV over 2-5 minutes on days 1 and 8 of cycles 1-4. Cycles 1-4 repeat every 21 days and subsequent cycles with atezolizumab and cobimetinib repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
| Cohort II (atezolizumab, eribulin) | Experimental | Drug: Atezolizumab, Drug: Eribulin, Other: Laboratory Biomarker Analysis, Other: Pharmacological StudyPatients receive atezolizumab IV over about 30-60 minutes every 3 weeks for cycles 1-6 and every 4 weeks for subsequent cycles, and eribulin IV over 2-5 minutes on days 1 and 8 of cycles 1-6. Cycles 1-6 repeat every 21 days and subsequent cycles with atezolizumab repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Signed informed consent form (ICF) and comply with the requirements of the study protocol
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- Confirmed diagnosis of inflammatory breast cancer according to international consensus criteria: (1) onset: rapid onset of breast erythema, edema, and/or peau d'orange, and/or warm breast, with or without an underlying breast mass (2) duration: history of such findings no more than 6 months (3) extent: erythema occupying at least 1/3 of whole breast (4) pathology: pathologic confirmation of invasive carcinoma
- Patients with recurrent or metastatic IBC after standard systemic therapy are eligible; patients who have disease progression while receiving standard anthracycline or taxane based neoadjuvant therapy are also eligible. a. patients with HER2-positive disease must have had at least 2 lines of anti-HER2 therapy, including Perjeta and Kadcyla; b. prior eribulin treatment is allowed
- At least one metastatic lesion amendable for biopsy (core, punch, or fine needle aspiration [FNA]); if the patient only has lymph nodes, these are considered amenable but will not be biopsied
Key exclusion criteria (33 listed)
- Any approved anticancer therapy for treatment purpose is not allowed, or need to be stopped at least 2 weeks prior to initiation of study treatment; however, the following are allowed: a. endocrine therapy (selective estrogen receptor modulator [SERM], aromatase inhibitor, fulvestrant) b. palliative radiotherapy for bone metastases > 1 week prior to study treatment c. stable brain metastasis and asymptomatic treated central nervous system (CNS) metastases are allowed, patient must show stable disease by CNS radiographic study >= 4 weeks from completion of radiotherapy and >= 2 weeks from discontinuation of corticosteroids
- Adverse events (AEs) from prior anticancer therapy that have not resolved to grade =< 1 except for alopecia and neuropathy
- Grade 3 or above neuropathy induced from prior treatment, that is not resolved to grade 2 or below despite best supportive care
- Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease
- Pregnancy, lactation, or breastfeeding
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AtezolizumabAlso: MPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280AGiven IV | Drug | Cohort I (atezolizumab, cobimetinib, eribulin), Cohort II (atezolizumab, eribulin) |
| CobimetinibAlso: Cotellic, GDC-0973, MEK Inhibitor GDC-0973, XL518Given PO | Drug | Cohort I (atezolizumab, cobimetinib, eribulin) |
| EribulinAlso: ER-086526Given IV | Drug | Cohort I (atezolizumab, cobimetinib, eribulin), Cohort II (atezolizumab, eribulin) |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Cohort I (atezolizumab, cobimetinib, eribulin), Cohort II (atezolizumab, eribulin) |
| Pharmacological StudyCorrelative studies | Other | Cohort I (atezolizumab, cobimetinib, eribulin), Cohort II (atezolizumab, eribulin) |
Primary outcome
Overall response rate (ORR)
Time frame: Up to 2 years
Calculated per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. ORR is defined as the rate of patients who achieved partial response or complete response as the best response. All tumor response will be evaluated by RECIST 1.1. The ORR will be estimated along with 95% confidence intervals. Logistic regression model will be used to assess other variables' effect on the best ORR.
7 secondary outcomes
Incidence of dose limiting toxicity (DLT) of cobimetinib and atezolizumab (safety lead-in)
Time frame: Up to 7 weeks
Clinical benefit rate (CBR)
Time frame: Up to 2 years
Duration of response (DOR)
Time frame: Up to 2 years
Progression free survival (PFS)
Time frame: From date of treatment start until date of first documented disease progression or death, whichever occurs first, assessed up to 2 years
Overall survival (OS)
Time frame: At 2 years
Pharmacodynamic markers
Time frame: Up to 2 years
Incidence of adverse events
Time frame: Up to 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jun 2026.
- M D Anderson Cancer CenterLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Vicente Valero principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Atezolizumab, Cobimetinib and Eribulin in people with Recurrent Breast Inflammatory Carcinoma and Stage IV Breast Inflammatory Carcinoma, run by M.D. Anderson Cancer Center at 1 site 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 20 inclusion and 33 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: under way, not looking for participants, as of the sponsor's last update on 10 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
This study is still under way. Results are not available in the source record yet.
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?
Overall response rate (ORR) (time frame: Up to 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 10 Jun 2026.