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Human Papillomavirus Positive Oropharyngeal Squamous Cell CarcinomaPhase 1NCT03575234

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

A Phase 1 study testing Cyclophosphamide, IRX-2 and Nivolumab in people with Human Papillomavirus Positive Oropharyngeal Squamous Cell Carcinoma and Stage II Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7, run by Emory University at 2 sites in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Cyclophosphamide, IRX-2 and Nivolumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
2 sitesUnited States
Study dates
1 Jul 2020to 31 Jan 2026
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 32Show fewer
  • 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
  • HPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA COHORT: Stage 1 (T1/2 N1) squamous cell carcinoma of the oropharynx associated with HPV as determined by p16 protein expression using immunohistochemistry (IHC) performed by a Clinical Laboratory Improvement Amendments [CLIA] approved laboratory
  • HPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA COHORT: No prior radiation above the clavicles
  • HPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA COHORT: Patients with a history of a curatively treated malignancy must be disease-free for at least two years prior to entry on study except for carcinoma in situ of cervix, melanoma in-situ (if fully resected), and/or non-melanomatous skin cancer
  • HPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA COHORT: Patients must not have evidence of extensive or "matted/fixed" pathologic adenopathy on preoperative imaging
  • HPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA COHORT: Hemoglobin > 9 g/dL
  • HPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA COHORT: Lymphocyte count > 500/µL
  • HPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA COHORT: Neutrophil count > 1500/µL
  • HPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA COHORT: Platelet count > 100,000/µL
  • HPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA COHORT: Serum albumin > 3.0 g/dL
  • HPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA COHORT: Aspartate aminotransferase (AST/ SGOT) and alanine aminotransferase (ALT/ SGPT) < 3 x the upper limits of normal (ULN)
  • HPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA COHORT: Alkaline phosphatase < 2 x ULN
  • HPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA COHORT: Prothrombin time (PT) and partial thromboplastin time (PTT) < 1.4 x ULN
  • HPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA COHORT: Calculated creatinine clearance > 50 mL/min
  • HPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA COHORT: Willing and able to give informed consent and adhere to protocol therapy
  • HPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA COHORT: ECOG performance status < 2
  • HPV-ASSOCIATED OROPHARYNX 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
  • HPV-ASSOCIATED OROPHARYNX 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

Who cannot join

  • 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
Show all 60Show fewer
  • 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
  • Direct extension of neck disease to involve the external skin
  • Direct extension to mediastinal structures
  • Regional metastases to the supraclavicular neck (low level VB and IVB)
  • 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:
  • Involvement of pterygopalatine fossa, maxillary sinus
  • 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
  • Direct extension of neck disease to involve the external skin
  • Direct extension to mediastinal structures
  • Regional metastases to the supraclavicular neck (low level VB and IVB)
  • 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

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Emory University Hospital Midtown

    Atlanta, Georgia, 30308

  • Emory University Hospital/Winship Cancer Institute

    Atlanta, Georgia, 30322

Other trials in United States

About this study

Official title: Phase I Neo-Adjuvant Nivolumab + IRX-2 Followed by Surgery for Resectable Oral Cavity Cancer or HPV-Associated Oropharynx Cancer

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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.

Being tested
Cyclophosphamide, IRX-2, Nivolumab, Surgery
Medical subject headings
Squamous Cell Carcinoma of Head and Neck

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CyclophosphamideDrug

    Also called Cytophosphane, Cytoxan, Neosar, Revimmune

    Given IV

  • IRX-2Biological

    Given SC

  • NivolumabBiological

    Also called BMS-936558, MDX-1106, ONO-4538, Opdivo

    Given IV

  • SurgeryProcedure or surgery

    Undergo surgery

Study groups in NCT03575234
Study groupRoleWhat they receive
Treatment (nivolumab, cyclophosphamide, IRX-2, surgery)ExperimentalParticipants 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.
Receives: Drug: Cyclophosphamide; Biological: IRX-2; Biological: Nivolumab; Procedure: Surgery

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to 4 years

  2. 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.

    Measured: Baseline up to 4 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Jul 2018
  2. Study start1 Jul 2020 (estimated)
  3. Primary completion31 Jan 2026 (estimated)
  4. Study completion31 Jan 2026 (estimated)

Why it stopped: funding and drug were withdrawn

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03575234
Sponsor's protocol ID
IRB00102105
Other IDs
NCI-2018-00411, Winship4300-18
Status last verified
Aug 2019
First submitted
21 Jun 2018
Last updated
28 Aug 2019
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Cyclophosphamide, IRX-2 and Nivolumab in people with Human Papillomavirus Positive Oropharyngeal Squamous Cell Carcinoma and Stage II Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7, run by Emory University at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 32 inclusion and 60 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 28 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of adverse events (AEs) described using Common Terminology Criteria for Adverse Events 4.03 (time frame: Up to 4 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03575234.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Aug 2019; AzTrials last refreshed its copy on 7 Nov 2026.

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