Nivolumab and Ipilimumab and Stereotactic Body Radiation Therapy in Treating Patients With Salivary Gland Cancers

NCT03749460 | Completed Phase 1 Results DMC FDA Drug

• 3 other identifiers: RG1718030NCI-2018-024738758
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I/II trial studies the side effects and how well nivolumab and ipilimumab works when given together with stereotactic body radiation therapy (SBRT) in treating patients with salivary gland cancers. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method can kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. Giving nivolumab and ipilimumab and SBRT may work better in treating patients with advanced salivary gland cancers.

Conditions

Metastatic Malignant Neoplasm in the Bone; Metastatic Malignant Neoplasm in the Lung; Salivary Gland Carcinoma; Stage IV Major Salivary Gland Cancer AJCC v8; Stage IVA Major Salivary Gland Cancer AJCC v8; Stage IVB Major Salivary Gland Cancer AJCC v8; Stage IVC Major Salivary Gland Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

• Incidence of Toxicity Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0

  Toxicities will be summarized as the number and percentage of patients with each type of toxicity, per Criteria for Adverse Events version 5.0

  From start of treatment through up to 100 days after the completion of study treatment (up to 16 months total)

Secondary Outcomes (3)

• Objective Response Rate (ORR)

  Up to 4 years

• Progression-free Survival (PFS)

  From the date of study enrollment, until disease progression or death, assessed up to 4 years

• Overall Survival (OS)

  From the date of study enrollment, until disease progression or death, assessed up to 4 years

Study Arms (1)

Treatment (nivolumab, ipilimumab, SBRT)

EXPERIMENTAL

Patients receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 2 weeks for up to 12 courses and then every 4 weeks for an additional 8 courses in the absence of disease progression or unacceptable toxicity. Patients also receive ipilimumab IV over 60 minutes on day 1. Treatment repeats every 6 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity. Beginning week 3, patients undergo 3 fractions of stereotactic body radiation therapy every other day in the absence of disease progression or unacceptable toxicity.

Biological: Nivolumab; Biological: Ipilimumab; Radiation: Stereotactic Body Radiation Therapy

Interventions

Nivolumab BIOLOGICAL

Given IV

Also known as: 946414-94-4, BMS-936558, MDX-1106, NIVO, ONO-4538, Opdivo, CMAB819, Nivolumab Biosimilar CMAB819

Treatment (nivolumab, ipilimumab, SBRT)

Ipilimumab BIOLOGICAL

Given IV

Also known as: 477202-00-9, Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, MDX-010, MDX-CTLA4, Yervoy, Biosimilar CS1002

Treatment (nivolumab, ipilimumab, SBRT)

Stereotactic Body Radiation Therapy RADIATION

Undergo SBRT

Also known as: SABR, SBRT, Stereotactic Ablative Body Radiation Therapy

Treatment (nivolumab, ipilimumab, SBRT)

Eligibility Criteria

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

You may qualify if:

• Histologically proven salivary gland carcinoma (World Health Organization \[WHO\], 2005) arising from a previous head and neck primary site, and located within the head and neck region, lung or bone, and who are not candidates for curative intent therapy
• Demonstrated disease progression during, or after discontinuation, of the most recent line of systemic therapy. For patients who have received no prior systemic therapy, demonstrated progression in the 3 months prior to trial participation assessed by the treating physician
• Have received any number lines of prior systemic therapy (including systemic therapy in the curative intent setting)
• Have a lesion/s deemed suitable by the treating physicians for stereotactic body radiation therapy (SBRT) with the intent of palliation or prevention of symptoms. This lesion must be:
• non-overlapping sites in the head and neck region OR
• Metastatic lesions outside the head and neck (H\&N) region in the lung or bone (a minimum of 1 and a maximum 5 lesions will be irradiated), provided there is no significant overlap between the lesions \*\* Patients should have RECIST 1.1 criteria measurable disease in addition to the lesion/s treated with SBRT. If the site/s of SBRT were previously radiated to high dose radiation therapy (RT) (\> 50Gy), there should be \> 6 month time interval between the last dose of radiation and the start of SBRT
• Have the ability to tolerate required SBRT-related procedures (e.g.: lie flat and hold position for treatment) as determined by the treating physician
• Be willing and able to provide written informed consent for the trial and comply with the study visit requirements
• Have measurable disease based on RECIST 1.1. (in addition to the lesion/s that will be treated with stereotactic radiation therapy)
• Have provided tissue from an archival tissue sample or newly obtained core or excisional biopsy of a tumor lesion. Tissue requirement will be waived if deemed contraindicated or not clinically available/accessible for resection per the treating physician (principal investigator \[PI\] approval required)
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
• Hemoglobin \>= 9.0 g/dL (performed within 28 days of treatment initiation)
• Absolute neutrophil count (ANC) \>= 1.5 x 10\^9 /L (\>= 1500 per mm\^3) (performed within 28 days of treatment initiation)
• Platelet count \>= 100 x 10\^9 /L (\>= 100,000 per mm\^3) (performed within 28 days of treatment initiation)
• Serum bilirubin =\< 1.5 x institutional upper limit of normal (ULN). This will not apply to subjects with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician (performed within 28 days of treatment initiation)

You may not qualify if:

• Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment
• Has a target lesion/s for SBRT that demonstrate any of the following:
• Located within 2 cm of the proximal bronchial tree
• \> 5 cm (\> 50 cc) in greatest dimension
• Has a target lesion/s in a region that previously received high dose radiation therapy (RT) (\> 50 Gy) demonstrating any of the following:
• Carotid artery encasement (\> 180 degrees) (due to risk of carotid blow out)
• Unprotected carotid artery (i.e. skin is directly over the carotid without intervening soft tissue, especially after prior neck dissection without a vascularized free flap) (due to risk of carotid blow out)
• Skin infiltration by tumor (due to risk of fistula)
• Located in the larynx/hypopharynx primaries (due airway threat)
• Treated with high dose radiation therapy (\> 50 Gy) within 6 months or less of trial enrollment
• Prior receipt of an anti-PD-1, anti-PDL1 or anti-CTLA4 immune checkpoint inhibitor
• Current or prior use of immunosuppressive medication within 14 days before the first dose of nivolumab or ipilimumab. The following are exceptions to this criterion:
• Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)
• Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
• Steroids as premedication for hypersensitivity reactions (e.g., computed tomography \[CT\] scan premedication)

Sponsors & Collaborators

• University of Washington: lead

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Salivary Gland Neoplasms

Interventions

Nivolumab; Ipilimumab; CTLA-4 Antigen; Radiosurgery

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; Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Results Point of Contact

• Title: Cristina Rodriguez
• Organization: University of Washington

rodrigcr@uw.edu

2066066748

Study Officials

• Cristina Rodriguez

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 19, 2018
• First Posted: November 21, 2018
• Study Start: January 15, 2019
• Primary Completion: November 5, 2022
• Study Completion: November 5, 2023
• Last Updated: December 29, 2023
• Results First Posted: December 29, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)