Atezolizumab, Cobimetinib, and Eribulin in Treating Patients With Chemotherapy Resistant Metastatic Inflammatory Breast Cancer

NCT03202316 | Active Not Recruiting Phase 2 FDA Drug

• 2 other identifiers: 2016-0890NCI-2017-01601
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief 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). 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.

Conditions

Recurrent Breast Inflammatory Carcinoma; Stage IV Breast Inflammatory Carcinoma

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to 2 years

Secondary Outcomes (7)

• Incidence of dose limiting toxicity (DLT) of cobimetinib and atezolizumab (safety lead-in)

  Up to 7 weeks

• Clinical benefit rate (CBR)

  Up to 2 years

• Duration of response (DOR)

  Up to 2 years

• Progression free survival (PFS)

  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)

  At 2 years

Study Arms (2)

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.

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.

Drug: Atezolizumab; Drug: Eribulin; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study

Interventions

Atezolizumab DRUG

Given IV

Also known as: MPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A, MPDL328OA, RG7446, RO5541267, Tecentriq

Cohort I (atezolizumab, cobimetinib, eribulin); Cohort II (atezolizumab, eribulin)

Cobimetinib DRUG

Given PO

Also known as: Cotellic, GDC-0973, MEK Inhibitor GDC-0973, XL518

Cohort I (atezolizumab, cobimetinib, eribulin)

Eribulin DRUG

Given IV

Also known as: ER-086526

Cohort I (atezolizumab, cobimetinib, eribulin); Cohort II (atezolizumab, eribulin)

Laboratory Biomarker Analysis OTHER

Correlative studies

Cohort I (atezolizumab, cobimetinib, eribulin); Cohort II (atezolizumab, eribulin)

Pharmacological Study OTHER

Correlative studies

Cohort I (atezolizumab, cobimetinib, eribulin); Cohort II (atezolizumab, eribulin)

Eligibility Criteria

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

You may qualify if:

• 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
• 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 \[PD window, day 1\])

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Inflammatory Breast Neoplasms

Interventions

atezolizumab; cobimetinib; eribulin

Condition Hierarchy (Ancestors)

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

Study Officials

• Vicente Valero

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 27, 2017
• First Posted: June 28, 2017
• Study Start: August 11, 2017
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: December 16, 2025

Record last verified: 2025-12

Locations

US (1)