Ipilimumab and Nivolumab in Treating Patients With Recurrent Stage IV HER2 Negative Inflammatory Breast Cancer

NCT02892734 | Terminated Phase 2 Results DMC FDA Drug

• 4 other identifiers: NU 16B07STU00203191P30CA060553NCI-2016-01038
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research study is to look at the efficacy (the effect on tumor) and the safety (the effect on body) of the study drugs when given as a combination in patients with metastatic recurrent epidermal growth factor receptor 2 (HER2) negative inflammatory breast cancer. This is a phase II study of 2 drugs used in combination: nivolumab and ipilimumab. The combination of these drugs is already approved by the Food and Drug Administration (FDA) to treat advanced melanoma (a type of skin cancer). Nivolumab and ipilimumab are not approved by the FDA for patients with metastatic recurrent HER2 negative inflammatory breast cancer, hence the treatment is considered experimental or investigational.

Conditions

HER2/Neu Negative; Recurrent Inflammatory Breast Carcinoma; Stage IV Breast Cancer; Stage IV Inflammatory Breast Carcinoma

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  PFS in patients with newly recurrent HER2 negative IBC treated with nivolumab and ipilimumab as evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 assessed from the date of first study treatment to the date of disease progression or death from any cause, assessed up to 2 years.

  Up to 2 years

Secondary Outcomes (4)

• Overall Response Rate (ORR)

  Every 12 weeks from treatment initiation for up to 2 years. Range of cycles patients completed 1-3 cycles (1 cycle =12 weeks)

• Clinical Benefit Rate (CBR)

  Every 12 weeks from treatment initiation for up to 2 years. Range of cycles patients completed 1-3 cycles (1 cycle =12 weeks)

• Overall Survival (OS)

  Up to 2 years

• Number of Adverse Events of Nivolumab and Ipilimumab Combination Treatment

  From the initiation of treatment until 12 weeks after study discontinuation. Range of cycles completed by patients 1-3 (1 cycle =12weeks)

Other Outcomes (4)

• iScore

  At baseline

• PD-L1 Expression Measured in Tissue Samples

  At baseline

• ctDNA Assessed by Exosome Analysis in Blood Samples

  At baseline

Study Arms (1)

Treatment (nivolumab, ipilimumab)

EXPERIMENTAL

Patients receive nivolumab IV over 30 minutes Q2W and ipilimumab IV over 90 minutes Q6W in the absence of disease progression or unacceptable toxicity.

Biological: Ipilimumab; Other: Laboratory Biomarker Analysis; Biological: Nivolumab

Interventions

Ipilimumab BIOLOGICAL

Given IV

Also known as: Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, MDX-010, MDX-CTLA4, Yervoy

Treatment (nivolumab, ipilimumab)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (nivolumab, ipilimumab)

Nivolumab BIOLOGICAL

Given IV

Also known as: BMS-936558, MDX-1106, NIVO, ONO-4538, Opdivo

Treatment (nivolumab, ipilimumab)

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically or cytologically confirmed stage IV breast carcinoma with a previous clinical diagnosis of IBC based on the presence of inflammatory changes in the involved breast, such as diffuse erythema and edema (peau d'orange), with or without an underlying palpable mass involving the majority of the skin of the breast; pathological evidence of dermal lymphatic invasion should be noted but is not required for diagnosis
• Patients must have local or metastatic recurrence of IBC after prior surgery
• Patients must have a metastatic tumor negative for HER2; the lack of HER2 overexpression by immunohistochemistry (IHC), is defined as 0 or 1+ where as hyperexpression is defined as 3+; if equivocal IHC, 2+, the tumor must be non-gene amplified by fluorescence in situ hybridization (FISH) performed upon the primary tumor or metastatic lesion (ratio \< 2 and HER2 copy number \< 4)
• Patients may have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension in accordance with RECIST criteria v. 1.1 OR non-measurable tumors; NOTE: Non-measurable tumors are small lesions (longest diameter \< 10mm or pathological lymph nodes with \>= 10 to \< 15 mm short axis); bone lesions, leptomeningeal disease, ascites, pleural/pericardial effusions, lymphangitis cutis/pulmonitis, inflammatory breast disease, and abdominal masses (not followed by computed tomography \[CT\] or magnetic resonance imaging \[MRI\]) are considered as non-measurable
• Patients must be in consideration for 1st line systemic therapy for recurrent IBC; NOTE: Patients must not have received chemotherapy in the metastatic setting, but adjuvant treatment after surgery is acceptable
• Patients must have confirmed availability of archival or freshly biopsied tumor tissue meeting protocol-defined specifications prior to study enrollment
• Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) status of 0-1; ECOG performance status 2 and 3 will be allowed only if decline in performance status is thought to be directly secondary to breast cancer disease burden by treating physician
• Patients must have adequate organ and bone marrow function within 14 days prior to registration, as defined below:
• Leukocytes \>= 2,000/mcL
• Absolute neutrophil count \>= 1,500/mcL, regardless of transfusion or growth factor support
• Platelets \>= 100,000/mcl, regardless of transfusion or growth factor support
• Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) (except patients with Gilbert syndrome or liver metastasis who can have total bilirubin \< 3.0 x ULN)
• Aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT)/ alanine aminotransferase (ALT) serum glutamate pyruvate transaminase (SGPT) =\< 2.5 x upper limit of normal (ULN) (or =\< 5 times ULN in case of liver metastasis)
• Serum creatinine of \< 3.0 x ULN (upper limit of normal)
• Patients with history of central nervous system (CNS) metastases are eligible if CNS disease has been stable for at least 6 weeks prior to study registration in the opinion of the investigator and do not require corticosteroids (of any dose) for symptomatic management; NOTE: Patients are not required to have CNS imaging prior to study entry

You may not qualify if:

• Patients must not have had chemotherapy or radiotherapy within 4 weeks prior to study registration
• Patients who already received chemotherapy for recurrent metastatic IBC are not eligible
• Patients who have not recovered to =\< grade 1 from adverse events due to agents administered more than 4 weeks earlier are not eligible
• Patients may not be receiving any other investigational agents
• Patients who have had prior exposure to immune checkpoint inhibitors are not eligible; please contact principal investigator, Ricardo Costaat 312-472-1234 for specific questions on potential interactions
• Programmed cell death protein 1 (PD-1) monoclonal antibody: pembrolizumab, pidilizumab, MEDI-0680, anti-PD-1 fusion protein AMP-224 (AMP-224), anti-PD-1 checkpoint inhibitor PF-06801591 (PF-06801591), anti-PD-1 monoclonal antibody BGB-A317 (BGB-A317), anti-PD-1 monoclonal antibody PDR001 (PDR001), anti-PD-1 monoclonal antibody REGN2810 (REGN2810), anti-PD-1 monoclonal antibody SHR-1210 (SHR-1210)
• PD-L1 monoclonal antibody: durvalumab, avelumab, anti-PD-L1 monoclonal antibody MDX-1105 (MDX-1105), atezolizumab, zirconium Zr 89-labeled anti-PD-L1 monoclonal antibody MPDL3280A (MPDL3280A)
• Cytotoxic T-lymphocyte protein 4 (CTLA4) monoclonal antibody: tremelimumab, abatacept
• Tumor necrosis factor receptor superfamily member 4 (OX40): agonistic anti-OX40 monoclonal antibody MEDI6383 (MEDI6383), agonistic anti-OX40 monoclonal antibody MEDI6469 (MEDI6469), anti-OX40 monoclonal antibody MEDI0562 (MEDI0562), oxelumab, anti-OX40 antibody PF-04518600 (PF-04518600)
• Patients with active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including chronic prolonged systemic corticosteroids (defined as corticosteroid use of duration one month or greater), should be excluded; these include but are not limited to patients with a history of:
• Immune related neurologic disease
• Multiple sclerosis
• Autoimmune (demyelinating) neuropathy
• Guillain-Barre syndrome
• Myasthenia gravis

Sponsors & Collaborators

• Northwestern University: lead
• Bristol-Myers Squibb: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Northwestern University

Chicago, Illinois, 60611, United States

Location

MeSH Terms

Conditions

Inflammatory Breast Neoplasms; Breast Neoplasms

Interventions

Ipilimumab; CTLA-4 Antigen; Nivolumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immune Checkpoint Proteins; Costimulatory and Inhibitory T-Cell Receptors; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Antigens, Differentiation, T-Lymphocyte; Antigens, Differentiation; Antigens, Surface; Antigens; Biological Factors; Biomarkers

Limitations and Caveats

Study closed due to slow accrual after only 3 patients were treated on study.

Results Point of Contact

• Title: William Gradishar, MD
• Organization: Northwestern University

w-gradishar@northwestern.edu

312 695 4541

Study Officials

• Ricardo Costa, M.D., M.Sc.

  Northwestern University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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: September 2, 2016
• First Posted: September 8, 2016
• Study Start: September 18, 2017
• Primary Completion: February 4, 2019
• Study Completion: February 4, 2019
• Last Updated: July 16, 2020
• Results First Posted: May 28, 2019

Record last verified: 2020-06

Locations

US (1)