Study of Nivolumab Plus Ipilimumab in Patients With Salivary Gland Cancer

• ClinicalTrials.gov Identifier: NCT03172624
• Recruitment Status: Active, not recruiting
• First Posted: June 1, 2017
• Last Update Posted: June 2, 2022
• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborator: Bristol-Myers Squibb
• Information provided by (Responsible Party): Memorial Sloan Kettering Cancer Center

Tracking Information

• First Submitted Date: May 30, 2017
• First Posted Date: June 1, 2017
• Last Update Posted Date: June 2, 2022
• Actual Study Start Date: May 26, 2017
• Estimated Primary Completion Date: May 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 30, 2017)

best overall response rate [ Time Frame: 2 years ]

using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1)

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of Nivolumab Plus Ipilimumab in Patients With Salivary Gland Cancer
• Official Title: A Phase II Study of Nivolumab Plus Ipilimumab in Patients With Recurrent/Metastatic Salivary Cancers
• Brief Summary: The purpose of this study is to find out what effects, good and/or bad, treatment with two drugs called nivolumab and ipilimumab have on the participant and salivary cancer.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

This is a phase II study evaluating the efficacy of nivolumab in combination with ipilimumab in patients with recurrent and/or metastatic (R/M) salivary gland cancers (SGCs). Patients will be enrolled to two cohorts: Cohort 1, patients with R/M adenoid cystic carcinoma ("ACC group"), and Cohort 2: patients with R/M SGC of any histology, except ACC ("non-ACC group").

Masking: None (Open Label)
Primary Purpose: Treatment

• Condition: Salivary Gland Cancer

Intervention

• Drug: Nivolumab
  nivolumab 3 mg/kg every 2 weeks
• Drug: Ipilimumab
  ipilimumab 1 mg/kg every 6 weeks (1 cycle= 6 weeks)

Study Arms

• Experimental: R/M adenoid cystic carcinoma (ACC)
  Enrolled patients will be treated with nivolumab 3 mg/kg every 2 weeks plus ipilimumab 1 mg/kg every 6 weeks (1 cycle= 6 weeks).
  Interventions:

  • Drug: Nivolumab
  • Drug: Ipilimumab
• Experimental: R/M SGC of any histology, except ACC (Non ACC)
  Enrolled patients will be treated with nivolumab 3 mg/kg every 2 weeks plus ipilimumab 1 mg/kg every 6 weeks (1 cycle= 6 weeks).
  Interventions:

  • Drug: Nivolumab
  • Drug: Ipilimumab

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

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: May 30, 2017): 64
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: May 2023
• Estimated Primary Completion Date: May 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Cohort 1 only: Patients must have pathologically or cytologically confirmed adenoid cystic carcinoma. Cancers arising from non-salivary gland primary sites are allowed.
• Patients must have pathologically or cytologically confirmed salivary gland cancer of any histology except for adenoid cystic carcinoma.
• Patients must have recurrent and/or metastatic disease not amenable to potentially curative surgery or radiotherapy.
• At least 2 weeks must have elapsed since the end of prior systemic treatment and/or 4 weeks since completion of radiotherapy with resolution of all treatment-related toxicity to NCI CTCAE Version 4.0 grade ≤1 (or tolerable grade 2) or back to baseline (except for alopecia, lymphopenia, or hypothyroidism) prior to starting study drug treatment. Any number of prior therapies for recurrent/metastatic salivary gland cancer are allowed.

NOTE: Patients previously treated with hormonal therapies (e.g., drugs targeting the androgen receptor) may continue these drugs prior to trials enrollment and concomitantly with study therapy.

• Patients must have RECIST v1.1 measurable disease.
• Cohort 1 and acinic cell carcinoma patients in Cohort 2 only: Patients must have documentation of a new or progressive lesion on a radiologic imaging study performed within 6 months prior to study enrollment (progression of disease over any interval is allowed) and/or new/worsening disease related symptoms within 6 months prior to study enrollment. Note: This assessment will be performed by the treating investigator. Evidence of progression by RECIST criteria is not required.
• Age ≥ 18 years.
• ECOG performance status 0 or 1 (or Karnofsky ≥ 70%).
• Patients must have tissue from the primary tumor or metastases available for correlative studies. Either a paraffin block or at least 20 unstained slides are acceptable (30 unstained slides would be ideal). (If less than twenty unstained slides are available and a paraffin bloc is not available, the patient may be able to participate at the discretion of the investigator.)
• Patients must agree to undergo two research biopsies of malignant lesions. Tumor tissue obtained prior to study consent or treatment as part of standard of care can also be submitted in lieu of performance of the first pre-treatment biopsy, if the Principal Investigator deems it to be of sufficient quantity/quality/timeliness. Patients may be exempt from biopsy if 1) the investigator or person performing the biopsy judges that no tumor is accessible for biopsy, 2) the investigator or person performing the biopsy feels that the biopsy poses too great of a risk to the patient, or 3) the patient's platelet count is <100,000/mcl or he/she cannot be safely removed from anti-coagulation therapy (if the anti-coagulation therapy needs to be temporarily held for the biopsy procedure). If the only tumor accessible for biopsy is also the only lesion that can be used for RECIST v1.1 response evaluation, then the patient may be exempt from biopsy. If the investigator deems a second research biopsy to be high risk after a patient has completed the first research biopsy, the patient may be exempt from the second biopsy.

• Screening laboratory values must meet the following criteria:

  • WBC ≥ 2000/μL
  • Neutrophils ≥ 1500/μL
  • Platelets ≥ 100 x10^3/μL
  • Hemoglobin > 9.0 g/dL
  • AST/ALT ≤ 3 x ULN
  • Total Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL)
  • Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 40 mL/min (if using the Cockcroft-Gault formula below):

Female CrCl = (140 - age in years) x weight in kg x 0.85 72 x serum creatinine in mg/dL

Male CrCl = (140 - age in years) x weight in kg x 1.00 72 x serum creatinine in mg/dL

• Women of childbearing potential (WOCBP)* must use appropriate method(s) of contraception. WOCBP should use an adequate method to avoid pregnancy for 23 weeks (30 days plus the time required for nivolumab to undergo five half-lives) after the last dose of investigational drug.

  • WOCBP is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes.

Women who are not of childbearing potential are not required to use contraception.

• Women of childbearing potential must have a negative serum or urine pregnancy test upon study entry.
• Men who are sexually active with women of child bearing potential must use adequate contraception upon study entry until 31 weeks after the last dose of study treatment. Men who are surgically sterile or azoospermic do not require contraception.

Exclusion Criteria:

• Symptomatic metastatic brain or leptomeningeal tumors (asymptomatic or treated metastatic brain or leptomeningeal tumors are allowed).
• Current or prior use of immunosuppressive doses of systemic corticosteroids (>10 mg/day prednisone equivalents) or other immunosuppressive medications within 2 weeks of study drug administration. NOTE: Subjects are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption). Physiologic replacement doses of systemic corticosteroids are permitted, even if >10 mg/day prednisone equivalents. A brief course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (eg, delayed-type hypersensitivity reaction caused by contact allergen) is permitted.
• Active, known, or suspected autoimmune disease within the past 2 years. NOTE: Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger
• Patients should be excluded if they have had prior systemic treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways.
• Patients should be excluded if they have a known history of testing positive for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus antibody (HCV antibody) indicating acute or chronic infection (those with treated hepatitis B or C infection and a negative viral load prior to study entry would be eligible)
• Patients should be excluded if they have a known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
• History of allergy to study drug components.
• History of severe hypersensitivity reaction to any monoclonal antibody.
• Women who are pregnant or breast-feeding.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03172624
• Other Study ID Numbers: 17-219
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: Memorial Sloan Kettering Cancer Center
• Original Responsible Party: Same as current
• Current Study Sponsor: Memorial Sloan Kettering Cancer Center
• Original Study Sponsor: Same as current
• Collaborators: Bristol-Myers Squibb

Investigators

• Principal Investigator: Alan Ho, MD, PhD; Memorial Sloan Kettering Cancer Center

• PRS Account: Memorial Sloan Kettering Cancer Center
• Verification Date: June 2022