Nivolumab and Ipilimumab in Treating Patients With Metastatic/Recurrent ACC of All Sites and Non-ACC Salivary Gland Cancer

NCT03146650 | Unknown Phase 2 Results DMC FDA Drug

• 4 other identifiers: NU 16N03STU00204579P30CA060553NCI-2017-00406
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies the efficacy (the effect on the tumor) and the safety (the effect on the body) of the study drugs when given as a combination in participants with this type of cancer. Another purpose of the study is to see which tumor markers (proteins in the blood that the body produces in response to the cancer) lead to better results in participants treated with the study drugs. Nivolumab and ipilimumab are antibodies, which are human proteins that recognize and attach to a part of the tumor and/or body's immune cells. They work in slightly different ways to activate the immune system and help the body's immune system to work against tumor cells. Nivolumab and ipilimumab are investigational because they are not approved by the FDA to be used for the type of cancer being studied.

Conditions

Major Salivary Gland Carcinoma; Minor Salivary Gland Carcinoma; Recurrent Salivary Gland Carcinoma; Stage IV Major Salivary Gland Carcinoma; Stage IVA Major Salivary Gland Carcinoma; Stage IVB Major Salivary Gland Carcinoma; Stage IVC Major Salivary Gland Carcinoma

Outcome Measures

Primary Outcomes (2)

• Progression-Free Survival

  Progression-Free Survival assessed per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) criteria at time of first study treatment. PFS defined as absence of death and of progressive disease. Progressive disease per RECIST v. 1.1 defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm (0.5 cm). The appearance of one or more new lesions is also considered progression. Response rates and 95% confidence intervals will be calculated using exact binomial probability distributions for discrete outcomes. Efficacy will be evaluated in all patients who receive at least one dose of study treatment and have had their disease re-evaluated.

  From the start of treatment and every 12 weeks during treatment, for up to two years, where 1 cycle =12 weeks/84 days, and range of cycles attempted was 1-11.

• Median Progression-free Survival

  Progression-Free Survival assessed per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) criteria at time of first study treatment. PFS defined as absence of death and of progressive disease. Progressive disease per RECIST v. 1.1 defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm (0.5 cm). The appearance of one or more new lesions is also considered progression. Response rates and 95% confidence intervals will be calculated using exact binomial probability distributions for discrete outcomes. Efficacy will be evaluated in all patients who receive at least one dose of study treatment and have had their disease re-evaluated.

  From the start of treatment and every 12 weeks during treatment, for up to two years, where 1 cycle =12 weeks/84 days, and range of cycles attempted was 1-11.

Secondary Outcomes (4)

• Response Rate (RR)

  On Cycle 2 Day 1, and every cycle thereafter (1 cycle = 12 weeks), about 27 months

• Clinical Benefit Rate (CBR)

  On Cycle 2 Day 1, and every cycle thereafter (1 cycle = 12 weeks), about 27 months

• Overall Survival (OS)

  Up to 2 years from start of treatment

• Number of Adverse Events Possibly Related to Study Drugs Graded 3, 4, and 5

  Up to 30 days after discontinuation, where range of cycles attempted was 1-11, where 1 Cycle = 84 days/12 weeks

Study Arms (1)

Treatment (nivolumab, ipilimumab)

EXPERIMENTAL

Patients receive nivolumab IV over 30 minutes on days 1, 15, 29, 43, 57, and 71 of course 1 and on days 1 and 15 of course 2, over 60 minutes on days 29 and 57 of course 2 and on days 1, 29, and 57 of subsequent courses. Patients also receive ipilimumab over 90 minutes on days 1 and 43. Courses repeat every 84 days in the absence of disease progression or unexpected 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: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically or cytologically confirmed metastatic/recurrent adenoid cystic carcinoma (ACC) or non-adenoid cystic carcinomas (non-ACC) of major or minor salivary glands
• Patients must have evidence of disease progression and cannot be a candidate for surgical treatment
• NOTE: Disease progression is defined as one of the following occurring within the 6 months prior to study entry:
• At least a 20% increase in radiologically or clinically measurable lesions
• Appearance of any new lesions or
• Symptomatic and/or deterioration in clinical status
• Patients must have received at least one prior line of systemic therapy
• NOTE: There is no limit to the number of prior therapies for stage IV disease
• NOTE: Patients should not be a candidate for surgical treatment
• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension in accordance with RECIST criteria v1.1
• Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) status of 0-2
• NOTE: ECOG performance status 3 will be allowed only if thought to be directly secondary to adenoid cystic carcinoma disease by treating physician
• Patients must have adequate organ and bone marrow function within 14 days prior to registration, as defined by: leukocytes \>= 2,000/mcL
• Patients must have adequate organ and bone marrow function within 14 days prior to registration, as defined by: absolute neutrophil count \>= 1,500/mcL, regardless of transfusion or growth factor support
• Patients must have adequate organ and bone marrow function within 14 days prior to registration, as defined by: platelets \>= 100,000/mcl, regardless of transfusion or growth factor support

You may not qualify if:

• Patients must not have had chemotherapy or radiotherapy =\< 28 days prior to study registration
• Patients who have not recovered to =\< grade 1 or tolerable grade 2 from adverse events due to agents administered \>= 28 days earlier are not eligible
• Patient must not be a candidate for surgical treatment or radiation
• Patients may not be receiving any other investigational agents =\< 28 days prior to registration
• Patients who have had prior exposure to immune checkpoint inhibitors are not eligible; please contact principal investigator, 312-926-4248 for specific questions on potential interactions
• NOTE: Immune checkpoint inhibitors working through OX40 are an exception (for example, MEDI6383, MEDI6469, MEDI0562, oxelumab, and PF-04518600) and are permitted \>= 28 days prior to study registration
• 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
• Systemic autoimmune disease such as SLE
• Connective tissue diseases
• Scleroderma

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

Related Publications (2)

• Chae YK, Duan R, Chung LI, Oh Y, Alexiev B, Shin S, Kim S, Helenowski I, Matsangou M, Villaflor V, Mahalingam D. Phase II Study of Nivolumab and Ipilimumab for Treatment of Metastatic/Recurrent Adenoid Cystic Carcinoma (ACC) of all Anatomic Sites of Origin and Other Malignant Salivary Gland Tumors. Cancer Med. 2025 Apr;14(7):e70724. doi: 10.1002/cam4.70724.

  PMID: 40166913 DERIVED

• Tchekmedyian V. Salivary Gland Cancers. Hematol Oncol Clin North Am. 2021 Oct;35(5):973-990. doi: 10.1016/j.hoc.2021.05.011.

  PMID: 34503735 DERIVED

MeSH Terms

Conditions

Salivary Gland Neoplasms

Interventions

Ipilimumab; CTLA-4 Antigen; Nivolumab

Condition Hierarchy (Ancestors)

Mouth Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Neoplasms; Mouth Diseases; Stomatognathic Diseases; Salivary Gland 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

The study closed without meeting the total accrual goal due to contract issues with the pharma company.

Results Point of Contact

• Title: Young Kwang Chae, MD, MPH, MBA
• Organization: Northwestern University, Feinberg School of Medicine

YCHAE@nm.org

312-926-4248

Study Officials

• Maria Matsangou, M.D.

  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: May 5, 2017
• First Posted: May 10, 2017
• Study Start: May 19, 2017
• Primary Completion: February 24, 2021
• Study Completion: August 11, 2025
• Last Updated: January 18, 2024
• Results First Posted: January 18, 2024

Record last verified: 2023-12

Locations

US (1)