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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2018-00411 | Registry Identifier | CTRP (Clinical Trial Reporting Program) | |
| Winship4300-18 | Other Identifier | Emory University Hospital/Winship Cancer Institute |
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funding and drug were withdrawn
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| Name | Class |
|---|---|
| Bristol-Myers Squibb | INDUSTRY |
| Brooklyn ImmunoTherapeutics, LLC | INDUSTRY |
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This phase I trial studies the side effects of nivolumab and IRX-2 and how well they work in treating participants with stage III-IVA oral cavity cancer or human papillomavirus (HPV)-positive oropharyngeal cancer that can be removed by surgery. Monoclonal antibodies, such as nivolumab, may interfere with the ability of tumor cells to grow and spread. IRX-2 may "turn on" the immune system and stimulate an immune response against tumor cells. Giving nivolumab and IRX-2 followed by surgery may work better at treating oral cavity and oropharyngeal cancer.
PRIMARY OBJECTIVES:
I. To determine the safety profile of combination immunotherapy, nivolumab + IRX-2, for HPV+ oropharyngeal squamous cell carcinoma (OPSCC) and HPV- oral cavity squamous cell carcinoma (OCSCC).
II. To assess the oncologic efficacy of neo-adjuvant immunotherapy using pathologic confirmation of response after surgical resection.
SECONDARY OBJECTIVES:
I. To correlate tumor microenvironment histopathology with pathologic findings, with progression free survival (PFS) and other outcome parameters in patients with resectable OPSCC and OCSCC after the above treatments.
II. To evaluate swallowing function before and after surgery and risk-adjusted adjuvant therapy.
III. To evaluate quality of life (QOL), swallowing perception and performance, voice outcomes, and head and neck symptoms.
OUTLINE: Participants receive nivolumab intravenously (IV) over 60 minutes on days 1 and 15, cyclophosphamide IV on day 1, and IRX-2 subcutaneously (SC) over 10 consecutive days between days 4-21 in the absence of disease progression or unacceptable toxicity. Beginning days 25-30, participants undergo surgery.
After completion of study treatment, patients are followed up at 3 months, every 3 months for 2 years, then every 6 months for 2 years.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment (nivolumab, cyclophosphamide, IRX-2, surgery) | Experimental | Participants receive nivolumab IV over 60 minutes on days 1 and 15, cyclophosphamide IV on day 1, and IRX-2 SC over 10 consecutive days between days 4-21 in the absence of disease progression or unacceptable toxicity. Beginning days 25-30, participants undergo surgery. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cyclophosphamide | Drug | Given IV |
|
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of adverse events (AEs) described using Common Terminology Criteria for Adverse Events 4.03 | Non-hematologic toxicities will be evaluated via the ordinal Common Toxicity Criteria (CTC) standard toxicity grading. Hematologic toxicity measures of thrombocytopenia, neutropenia, and leukopenia will be assessed using continuous variables as the outcome measures (primarily nadir) as well as categorization via CTC standard toxicity grading. Overall toxicity incidence as well as toxicity profiles by dose level and patient will be explored and summarized. | Up to 4 years |
| Change in tumor size determined by central radiology review by radiologists blinded to the treatment regimen | Tumor changes will be determined by a comparison of the imaging studies (contrast-enhanced computed tomography [CECT] or magnetic resonance imaging [MRI]) obtained pre-treatment and just prior to surgery. Percent changes in tumor size will be determined by radiology at the site. If the change is not clear to the radiologist at the site, then the PI must be notified and two radiologists at Emory will be asked to independently review the scans and a decision will be made. | Baseline up to 4 years |
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Inclusion Criteria:
Exclusion Criteria:
ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Prior surgery, radiation therapy, or chemotherapy other than biopsy or emergency procedure required for supportive care
ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-cytotoxic T-lymphocyte associated protein 4 (anti-CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Prior treatment with cetuximab or epidermal growth factor receptor (EGFR) inhibitors in any treatment setting
ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Any medical contraindications or previous therapy that would preclude treatment with either nivolumab, IRX-2, the surgery, reconstruction or adjuvant therapy required to treat the oral tumor appropriately
ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Clinical status of either subject or tumor such that administration of 10 day neoadjuvant IRX-2 before surgery would be medically inappropriate
ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Primary tumor of the oropharynx
ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Tumor involvement of the following sites or any of these signs or symptoms likely to be associated with T4b cancer:
ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Any investigational agent within the previous 30 days
ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Daily administration of systemic immunosuppressive therapy or corticosteroids (except in physiological doses for hormone deficiency) during the previous 30 days
ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Chronic anticoagulation, not including aspirin, but including heparins, warfarin, oral anticoagulation or other platelet function inhibitors
ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Symptomatic cardiopulmonary disease (including congestive heart failure and hypertension), coronary artery disease, serious arrhythmia or chronic lung disease; patients with these conditions who are stable with relatively minor symptoms and who are appropriate candidates for surgical treatment of their tumor need not be excluded
ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Myocardial infarction within the last 3 months
ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Evidence of distant metastases (M1 disease) or other concurrent primary malignancy
ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Known infection with hepatitis B, hepatitis C, or human immunodeficiency virus (HIV)
ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Signs or symptoms of systemic infection (use of antibiotics to treat superficial infection or contamination of tumor shall not, by itself, be considered evidence of infection
ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Stroke or other symptoms of cerebral vascular insufficiency within the last 3 months
ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Allergy to ciprofloxacin (or other quinolones) and acetylsalicylic acid
ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Previous diagnosis of invasive cancer from which the individual is NOT disease-free AND that has required treatment within the past 5 years, except for superficial skin, cervical cancer in-situ, well-differentiated thyroid or early stage prostate or bladder cancer (i.e., treatment with curative intent and long term disease-free expectations)
ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Prior axillary dissection
ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: History of pneumonitis or interstitial lung disease
HPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA COHORT: Prior surgery, radiation therapy, or chemotherapy other than biopsy or emergency procedure required for supportive care
HPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA COHORT: Prior 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 co-stimulation or checkpoint pathways
HPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA COHORT: Any medical contraindications or previous therapy that would preclude treatment with either nivolumab or IRX-2 or the surgery, reconstruction or adjuvant therapy required to treat the oropharynx tumor appropriately
HPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA COHORT: Tumor of the oral cavity
HPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA COHORT: Tumor involvement of the following sites or any of these signs or symptoms likely to be associated with T4b cancer:
HPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA COHORT: Any investigational agent within the previous 30 days
HPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA COHORT: Daily administration of systemic immunosuppressive therapy or corticosteroids (except in physiological doses for hormone deficiency) during the previous 30 days
HPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA COHORT: Chronic anticoagulation, not including aspirin, but including heparins, warfarin, oral anticoagulation or other platelet function inhibitors
HPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA COHORT: Symptomatic cardiopulmonary disease (including congestive heart failure and hypertension), coronary artery disease, serious arrhythmia or chronic lung disease; patients with these conditions who are stable with relatively minor symptoms and who are appropriate candidates for surgical treatment of their tumor need not be excluded
HPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA COHORT: Myocardial infarction within the last 3 months
HPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA COHORT: Evidence of distant metastases (M1 disease) or other concurrent primary malignancy
HPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA COHORT: Known infection with hepatitis B, hepatitis C, or HIV
HPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA COHORT: Signs or symptoms of systemic bacterial infection (use of antibiotics to treat superficial infection or contamination of tumor shall not, by itself, be considered evidence of infection)
HPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA COHORT: Stroke or other symptoms of cerebral vascular insufficiency within the last 3 months
HPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA COHORT: Allergy to ciprofloxacin (or other quinolones), acetylsalicylic acid
HPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA COHORT: Previous diagnosis of invasive cancer from which the individual is NOT disease-free AND that has required treatment within the past 5 years, except for superficial skin, cervical cancer in-situ, well-differentiated thyroid or early stage prostate or bladder cancer (i.e., treatment with curative intent and long term disease-free expectations)
HPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA COHORT: Prior axillary dissection
HPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA COHORT: History of pneumonitis or interstitial lung disease
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| Name | Affiliation | Role |
|---|---|---|
| Mihir Patel, MD | Emory University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Emory University Hospital Midtown | Atlanta | Georgia | 30308 | United States | ||
| Emory University Hospital/Winship Cancer Institute |
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| IRX-2 | Biological | Given SC |
|
| Nivolumab | Biological | Given IV |
|
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| Surgery | Procedure | Undergo surgery |
|
| Atlanta |
| Georgia |
| 30322 |
| United States |
| ID | Term |
|---|---|
| D000077195 | Squamous Cell Carcinoma of Head and Neck |
| ID | Term |
|---|---|
| D002294 | Carcinoma, Squamous Cell |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006258 | Head and Neck Neoplasms |
| D009371 | Neoplasms by Site |
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| ID | Term |
|---|---|
| D003520 | Cyclophosphamide |
| C114857 | IRX 2 |
| D000077594 | Nivolumab |
| D013514 | Surgical Procedures, Operative |
| ID | Term |
|---|---|
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
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