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Combining Immunotherapy Salvage Surgery & IORT Tx Persistent/Recurrent Head & Neck Cancer

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ClinicalTrials.gov Identifier: NCT04754321
Recruitment Status : Recruiting
First Posted : February 15, 2021
Last Update Posted : December 5, 2022
Sponsor:
Information provided by (Responsible Party):
Dukagjin Blakaj, Ohio State University Comprehensive Cancer Center

Brief Summary:
This phase I trial is to find out the possible side effects of pembrolizumab and radiation therapy before and during surgery in treating patients with head and neck squamous cell cancer that remains despite treatment (persistent) or has come back (recurrent). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy x-rays or protons to kill tumor cells and shrink tumors. Giving pembrolizumab and radiation therapy before and during surgery may kill more tumor cells.

Condition or disease Intervention/treatment Phase
Head and Neck Carcinoma of Unknown Primary Locally Recurrent Head and Neck Squamous Cell Carcinoma Recurrent Laryngeal Squamous Cell Carcinoma Recurrent Oral Cavity Squamous Cell Carcinoma Recurrent Pharyngeal Squamous Cell Carcinoma Resectable Head and Neck Squamous Cell Carcinoma Radiation: External Beam Radiation Therapy Radiation: Intraoperative Radiation Therapy Biological: Pembrolizumab Other: Quality-of-Life Assessment Procedure: Salvage Surgery Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 45 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: HNSALV Trial: Combining Immunotherapy With Salvage Surgery and IORT for Treatment of Persistent/Recurrent Head and Neck Cancers
Actual Study Start Date : May 12, 2022
Estimated Primary Completion Date : December 31, 2024
Estimated Study Completion Date : December 31, 2025


Arm Intervention/treatment
Experimental: Arm A (pembrolizumab, salvage surgery, IORT)
Patients receive pembrolizumab IV on day 1 of week 1, and undergo salvage surgery during week 4. Beginning week 8, patients receive pembrolizumab IV every 3 weeks for up to 18 doses in the absence of disease progression or unacceptable toxicity. Patients also undergo IORT for 1 fraction during week 9. Treatment with pembrolizumab may continue beyond initial progression per investigator-assessed clinical benefit and if the patient is tolerating pembrolizumab.
Radiation: Intraoperative Radiation Therapy
Undergo IORT
Other Names:
  • Intraoperative Radiotherapy
  • IORT
  • radiotherapy, intraoperative

Biological: Pembrolizumab
Given IV
Other Names:
  • Keytruda
  • Lambrolizumab
  • MK-3475
  • SCH 900475

Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

Procedure: Salvage Surgery
Undergo salvage surgery
Other Names:
  • Rescue Surgery
  • Salvage Resection
  • Salvage Surgical Resection
  • Surgical Salvage

Experimental: Arm B (pembrolizumab, EBRT, salvage surgery, IORT)
Patients receive pembrolizumab IV on day 1 of week 1, and undergo low dose EBRT for 2 fractions on 2 consecutive days during week 4. Patients also undergo salvage surgery during week 8. Beginning week 11, patients receive pembrolizumab IV every 3 weeks for up to 18 doses in the absence of disease progression or unacceptable toxicity. Patients also undergo IORT for 1 fraction during week 11. Treatment with pembrolizumab may continue beyond initial progression per investigator-assessed clinical benefit and if the patient is tolerating pembrolizumab.
Radiation: External Beam Radiation Therapy
Undergo EBRT
Other Names:
  • Definitive Radiation Therapy
  • EBRT
  • External Beam Radiation
  • External Beam Radiotherapy
  • External Beam RT
  • external radiation
  • External Radiation Therapy
  • external-beam radiation
  • Radiation, External Beam

Radiation: Intraoperative Radiation Therapy
Undergo IORT
Other Names:
  • Intraoperative Radiotherapy
  • IORT
  • radiotherapy, intraoperative

Biological: Pembrolizumab
Given IV
Other Names:
  • Keytruda
  • Lambrolizumab
  • MK-3475
  • SCH 900475

Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

Procedure: Salvage Surgery
Undergo salvage surgery
Other Names:
  • Rescue Surgery
  • Salvage Resection
  • Salvage Surgical Resection
  • Surgical Salvage

Experimental: Arm C (pembrolizumab, EBRT, salvage surgery, IORT)
Patients receive pembrolizumab IV on day 1 of week 1, and undergo high dose EBRT for 2 fractions on 2 consecutive days during week 4. Patients also undergo salvage surgery during week 8. Beginning week 11, patients receive pembrolizumab IV every 3 weeks for up to 18 doses in the absence of disease progression or unacceptable toxicity. Patients also undergo IORT for 1 fraction during week 11. Treatment with pembrolizumab may continue beyond initial progression per investigator-assessed clinical benefit and if the patient is tolerating pembrolizumab.
Radiation: External Beam Radiation Therapy
Undergo EBRT
Other Names:
  • Definitive Radiation Therapy
  • EBRT
  • External Beam Radiation
  • External Beam Radiotherapy
  • External Beam RT
  • external radiation
  • External Radiation Therapy
  • external-beam radiation
  • Radiation, External Beam

Radiation: Intraoperative Radiation Therapy
Undergo IORT
Other Names:
  • Intraoperative Radiotherapy
  • IORT
  • radiotherapy, intraoperative

Biological: Pembrolizumab
Given IV
Other Names:
  • Keytruda
  • Lambrolizumab
  • MK-3475
  • SCH 900475

Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

Procedure: Salvage Surgery
Undergo salvage surgery
Other Names:
  • Rescue Surgery
  • Salvage Resection
  • Salvage Surgical Resection
  • Surgical Salvage




Primary Outcome Measures :
  1. Incidence of adverse events [ Time Frame: Up to 100 days after last dose of study drug ]
    Evaluated using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0. Summarized by treatment group. All on-study adverse events (AEs), treatment-related AEs, serious (S)AEs, and treatment-related SAEs will be tabulated using worst grade per NCI CTCAE version 4.0 criteria by system organ class and preferred term. On-study lab parameters including hematology, chemistry, liver function, and renal function will also be summarized using worst grade NCI CTCAE v 4.0 criteria. Toxicity will be measured as the rate of grade 3 and 4 adverse events and will be calculated through using the exact binomial distribution method with a 2- sided 95% confidence interval.

  2. Health related quality of life [ Time Frame: Up to 5 years ]
    Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30. Analysis will be performed in all randomized participants who have an assessment at baseline and at least one follow-up assessment using linear mixed model for repeated measures to model the changes overtime for each arm.


Secondary Outcome Measures :
  1. Objective-response rate (ORR) [ Time Frame: Up to 5 years ]
    ORR including complete response rate, partial response rate, and stable disease rate will be calculated using the exact binomial distribution method with a 2- sided 95% confidence interval among patients who obtain a least one dose of study drug.

  2. Local control rate [ Time Frame: From the first day of therapy to the occurrence of a local and/or regional recurrence (whichever comes first), and death from any cause other than distant metastasis, assessed up to 24 months ]
    Analyses will be conducted using Kaplan-Meier method for each arm. The hazard ratio and corresponding two-sided 95% CI will be estimated using a Cox proportional hazards model, with treatment group as a single covariate.

  3. Overall survival [ Time Frame: Up to 5 years ]
    Analyses will be conducted using Kaplan-Meier method for each arm. The hazard ratio and corresponding two-sided 95% CI will be estimated using a Cox proportional hazards model, with treatment group as a single covariate.

  4. Progression-free survival (PFS) [ Time Frame: From the first day of the therapy to the appearance of local or regional recurrence, distant metastases, secondary primary cancer or death from any cause, assessed up to 24 months ]
    Analyses will be conducted using Kaplan-Meier method for each arm. The PFS medians with 95% confidence intervals (CIs), and PFS at 6, 12, and 24 months with 95% CIs will be estimated a two-sided log-rank test. The hazard ratio and corresponding two-sided 95% CI will be estimated using a Cox proportional hazards model, with treatment group as a single covariate, stratified by the above factors.

  5. PD-L1 expression [ Time Frame: Up to 5 years ]
    A Cox proportional hazards model will be used to test the interaction between PD-L1 expression (positive vs negative) and treatment arm.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Pathologically confirmed either persistent and/ or locoregionally recurrent HNSCC of oral cavity, pharynx, larynx, unknown primary head and neck (H&N) squamous cell carcinoma
  • Resectable disease as determined by the surgeon and team
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) < 2
  • At least 18 years of age
  • Adequate hematologic, renal, and hepatic function
  • Must have at least 2 week washout period from prior therapy
  • Willingness and ability to provide informed consent
  • Negative pregnancy test for females of reproductive potential
  • Patients who plan to or have undergone therapy for their cancer, such as surgery and/or chemotherapy and/or radiotherapy and recurred
  • Disease measurable by computed tomography (CT) or magnetic resonance imaging (MRI)
  • Prior chemotherapy will be allowed
  • Prior radiation therapy will be allowed
  • Tumor tissue from resected site of disease must be provided for biomarker analyses, in addition to urine and blood sample as scheduled per protocol
  • White blood cell (WBC) >= 2000/uL (obtained within 14 days of randomization)
  • Neutrophils >= 1500/uL (obtained within 14 days of randomization)
  • Platelets >= 100 x10^3/uL (obtained within 14 days of randomization)
  • Hemoglobin > 9.0 g/dL (obtained within 14 days of randomization)
  • Serum creatinine =< 1.5 x upper limit of normal (ULN) or calculated creatinine clearance (CrCl) >= 40 mL/min (Cockcroft and Gault or Wright formula may be used according to local practice) (obtained within 14 days of randomization)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x ULN (obtained within 14 days of randomization)
  • Total Bilirubin =< 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL) (obtained within 14 days of randomization)
  • 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 nivolumab
  • Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG])
  • Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year. Men who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 31 weeks after the last dose of investigational product

Exclusion Criteria:

  • Requirement of immunosuppressive therapy within 14 days of randomization
  • Salivary gland carcinomas, lip carcinoma, adenocarcinoma of the skin
  • Prior use of immune checkpoint blockade agent
  • History of human immunodeficiency virus (HIV), hepatitis B, C: Participants who test positive for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection, those who test positive for human immunodeficiency virus (HIV) or have known acquired immunodeficiency syndrome (AIDS)
  • Unresectable disease, as determined by the surgeon and team
  • Subjects with history of grade 3 toxicity with prior immunotherapy
  • Patients with untreated brain metastasis/es
  • Subjects with active, known, or suspected autoimmune disease with the exception of skin diseases that do not require systemic treatment (such as alopecia) and type I diabetes
  • Breastfeeding women
  • Additional prior malignancy within the previous 3 years (treated or untreated, except for skin carcinomas treated with excision alone and carcinoma in situ of the cervix)
  • Palliative radiotherapy less than 14 days prior to first dose of study drug
  • Any history of hypersensitivity to any of the trial medications or solutions they are mixed into
  • Poorly controlled or serious medical or psychiatric illness likely to interfere with participation and/or compliance in this clinical trial
  • Prisoners or subjects who are involuntarily incarcerated
  • Patients not available for follow-up/future contact
  • Note: Patients on this protocol are not excluded from participation in other clinical trials

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04754321


Contacts
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Contact: The Ohio State University Comprehensive Cancer Center 800-293-5066 OSUCCCClinicaltrials@osumc.edu

Locations
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United States, Ohio
Ohio State University Comprehensive Cancer Center Recruiting
Columbus, Ohio, United States, 43210
Contact: Dukagjin M. Blakaj, MD, PhD    614-366-2729    Dukagjin.Blakaj@osumc.edu   
Principal Investigator: Dukagjin M. Blakaj, MD, PhD         
Sponsors and Collaborators
Ohio State University Comprehensive Cancer Center
Investigators
Layout table for investigator information
Principal Investigator: Dukagjin M Blakaj, MD, PhD Ohio State University Comprehensive Cancer Center
Additional Information:
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Responsible Party: Dukagjin Blakaj, Principal Investigator, Ohio State University Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT04754321    
Other Study ID Numbers: OSU-20297
NCI-2021-00036 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
First Posted: February 15, 2021    Key Record Dates
Last Update Posted: December 5, 2022
Last Verified: December 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Squamous Cell
Squamous Cell Carcinoma of Head and Neck
Recurrence
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Disease Attributes
Pathologic Processes
Neoplasms, Squamous Cell
Head and Neck Neoplasms
Neoplasms by Site
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents