Nivolumab & IRX-2 With Surgery for Resectable Stage III-IVA Oral Cavity Cancer or HPV-Positive Oropharyngeal Cancer

NCT03575234 | Withdrawn Phase 1 DMC FDA Drug

• 3 other identifiers: IRB00102105NCI-2018-00411Winship4300-18
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Human Papillomavirus Positive Oropharyngeal Squamous Cell Carcinoma; Stage II Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage III Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVA Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage III Oropharyngeal Squamous Cell Carcinoma AJCC v7

Outcome Measures

Primary Outcomes (2)

• 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

Study Arms (1)

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.

Drug: Cyclophosphamide; Biological: IRX-2; Biological: Nivolumab; Procedure: Surgery

Interventions

Cyclophosphamide DRUG

Given IV

Also known as: Cytophosphane, Cytoxan, Neosar, Revimmune

Treatment (nivolumab, cyclophosphamide, IRX-2, surgery)

IRX-2 BIOLOGICAL

Given SC

Treatment (nivolumab, cyclophosphamide, IRX-2, surgery)

Nivolumab BIOLOGICAL

Given IV

Also known as: BMS-936558, MDX-1106, ONO-4538, Opdivo

Treatment (nivolumab, cyclophosphamide, IRX-2, surgery)

Surgery PROCEDURE

Undergo surgery

Treatment (nivolumab, cyclophosphamide, IRX-2, surgery)

Eligibility Criteria

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

You may qualify if:

• ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Pathologically confirmed (histology or cytology), p16-negative (by immunohistochemistry \[IHC\]) stage II, III, or IVA squamous cell cancer of the oral cavity (excluding lip)
• ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Disease is surgically resectable with curative intent
• ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Hemoglobin \> 9 g/dL
• ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Lymphocyte count \> 500/µL
• ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Neutrophil count \> 1500/µL
• ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Platelet count \> 100,000/µL
• ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Serum albumin \> 3.0 g/dL
• ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Aspartate aminotransferase (AST/serum glutamic-oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT/ serum glutamate pyruvate transaminase \[SGPT\]) \< 3 x the upper limits of normal (ULN)
• ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Alkaline phosphatase \< 2 x ULN
• ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Prothrombin time (PT) and partial thromboplastin time (PTT) \< 1.4 x ULN
• ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Calculated creatinine clearance \> 50 mL/min
• ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Willing and able to give informed consent and adhere to protocol therapy
• ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Eastern Cooperative Oncology Group (ECOG) performance status \< 2
• ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Female of childbearing potential (less than 12 months post-menopausal) or male with a partner of childbearing potential either agrees to be abstinent or uses a medically acceptable form of birth control during the study and for a period of 1 year
• ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Negative urine/serum pregnancy test (female participants only) at the time of screening and within 24 hours of study treatment, if applicable

You may not qualify if:

• 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:
• Involvement of pterygopalatine fossa, maxillary sinus, or facial skin
• Gross extension of tumor to the skull base
• Pterygoid plate erosion
• Sphenoid bone or foramen ovale involvement
• Direct extension to involve prevertebral fascia
• Extension to superior nasopharynx or Eustachian tube
• Direct extension into the neck with involvement of the deep neck musculature (neck node fixation)
• Suspected invasion (encasement) of the common or internal carotid arteries; encasement will be assessed radiographically and will be defined as tumor surrounding the carotid artery 270 degrees or greater

Sponsors & Collaborators

• Emory University: lead
• Bristol-Myers Squibb: collaborator
• Brooklyn ImmunoTherapeutics, LLC: collaborator

Study Sites (2)

Emory University Hospital Midtown

Atlanta, Georgia, 30308, United States

Location

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

Cyclophosphamide; IRX 2; Nivolumab; Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Mihir Patel, MD

  Emory University

  PRINCIPAL INVESTIGATOR

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: Principal Investigator

Study Record Dates

• First Submitted: June 21, 2018
• First Posted: July 2, 2018
• Study Start: July 1, 2020
• Primary Completion: January 31, 2026
• Study Completion: January 31, 2026
• Last Updated: August 28, 2019

Record last verified: 2019-08

Locations

US (2)