Ipilimumab, Nivolumab, and Radiation Therapy in Treating Patients With HPV Positive Advanced Oropharyngeal Squamous Cell Carcinoma

NCT03799445 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: 2018-0381NCI-2018-03260
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies the side effects and best dose of ipilimumab, nivolumab, and radiation therapy and how well they work in treating patients with advanced human papillomavirus (HPV) positive oropharyngeal squamous cell carcinoma. Immunotherapy with monoclonal antibodies, such as ipilimumab and nivolumab, 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 to kill tumor cells and shrink tumors. Giving ipilimumab, nivolumab, and radiation therapy may work better in treating patients with HPV positive oropharyngeal squamous cell carcinoma.

Conditions

Oropharyngeal Basaloid Carcinoma; Pathologic Stage I HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8; Pathologic Stage II HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8; Posterior Tongue Squamous Cell Carcinoma; Soft Palate Squamous Cell Carcinoma; Clinical Stage I HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8; Clinical Stage II HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8; Human Papillomavirus Positive Oropharyngeal Squamous Cell Carcinoma; Stage III Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7; Tonsillar Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (2)

• Radiographic (RECIST) Response

  Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v.1.1) for target lesions and assessed by CT or MRI: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>= 30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient growth to qualify for PD; Progressive Disease (PD), \>= 20% increase in the sum of the longest diameter with an absolute increase of at least 5 mm or the appearance of new lesions

  6 months post completion of radiation therapy (approximately 9 months post start of treatment)

• Pathologic Response -- Percent Viable Tumor Change

  Pathologic response refers to the evaluation of how much a tumor has shrunk after treatment by the pathologist on trial examining tissue samples under a microscope. Tissue samples from baseline and at follow up were evaluated for tumor response. Percent viable tumor change is calculated using viable tumor data collected at the biopsy to the biopsy at the end of Cycle 1 of treatment.

  From first registration on trial (baseline biopsy) to post Cycle 1 of IO (6 weeks after start of treatment)

Secondary Outcomes (3)

• Toxicity (Number of Adverse Events)

  time of first drug administration to 30 days after last drug administration

• Survival Analysis -- Progression Free Survival

  12 month post treatment follow up (15 months post treatment start), 18 month post treatment follow up (21 months post treatment start), 24 month post treatment follow up (27 months post treatment start)

• Survival Analysis -- Overall Survival (Percentage of Participants Alive at 12 Months, 18 Months, and 24 Months)

  12 month post treatment follow up (15 months post treatment start), 18 month post treatment follow up (21 months post treatment start), 24 month post treatment follow up (27 months post treatment start)

Study Arms (1)

Treatment (nivolumab, ipilimumab, IMRT)

EXPERIMENTAL

Patients receive nivolumab IV over 30 minutes on days 1, 15, and 29 and ipilimumab IV over 30 minutes on day 1. Treatment repeats every for 6 weeks for 2 cycles in the absence of disease progression or unacceptable toxicity. Beginning on day 1 of cycle 2, patients also undergo IMRT 5 days a week (Monday-Friday) for 6 weeks in the absence of disease progression or unacceptable toxicity.

Radiation: Intensity-Modulated Radiation Therapy; Biological: Ipilimumab; Biological: Nivolumab; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

Interventions

Intensity-Modulated Radiation Therapy RADIATION

Undergo IMRT

Also known as: IMRT, Intensity Modulated RT, Intensity-Modulated Radiotherapy

Treatment (nivolumab, ipilimumab, IMRT)

Ipilimumab BIOLOGICAL

Given IV

Also known as: Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, MDX-010, MDX-CTLA4, Yervoy

Treatment (nivolumab, ipilimumab, IMRT)

Questionnaire Administration OTHER

Ancillary studies

Treatment (nivolumab, ipilimumab, IMRT)

Nivolumab BIOLOGICAL

Given IV

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

Treatment (nivolumab, ipilimumab, IMRT)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (nivolumab, ipilimumab, IMRT)

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically newly confirmed diagnosis of squamous cell carcinoma (including the histological variants of papillary or basaloid) of the oropharynx (tonsil, base of tongue, soft palate, or oropharyngeal walls)
• Clinical American Joint Committee on Cancer (AJCC) 7th edition stage T1N2a-N2CM0, T2N1-N2CM0, T3N0-N2CM0, equivalent to AJCC 8th edition stage 1 and 2 (T1 N2, T2 N1-N2, T3 N0-N2) excluding T1N0-N1 and T2N0 (Brian O'Sullivan et al. 2016)
• Tumor positive for p16 immunohistochemistry (IHC) (defined as greater than 70% strong nuclear or nuclear and cytoplasmic staining of tumor cells) and HPV DNA in situ hybridization or HPV messenger ribonucleic acid (mRNA) RNAScope. Repeat samples may be required if adequate diagnostic tissue is unavailable for testing
• Zubrod Performance Status of 0-1
• Patients must have radiographically evident measurable disease at the primary site or at nodal stations per response evaluation criteria in solid tumors (Response Evaluation Criteria in Solid Tumors \[RECIST\]) 1.1 documented by diagnostic quality CT or magnetic resonance imaging (MRI) of the neck with contrast within 28 days prior to registration; a FDG-PET/CT of the neck performed for the purposes of radiation planning is acceptable as a substitute if the CT is of diagnostic quality
• Diagnostic quality cross sectional imaging of the thorax within 28 days prior to registration. A 18-FDG-PET/CT or conventional CT are acceptable
• FDG-PET/CT of the neck is required within 28 days prior to registration for comparison to post treatment FDG-PET/CT. Note: Repeat imaging for variability within 96 hours of this time frame should be allowed to avoid unnecessary re-imaging and its financial and potential physical consequences for patients
• History and physical exam within 1 month prior to registration
• Fiberoptic exam with laryngopharyngoscopy (mirror and/or fiberoptic and/or direct procedure) by radiation oncologist, medical oncologist or ear, nose, throat (ENT)/head and neck surgeons within 28 days prior to registration
• Absolute neutrophil count (ANC) \>= 1,500 cells/mm\^3 (within 2 weeks prior to registration)
• Platelets \>= 100,000 cells/mm\^3 (within 2 weeks prior to registration)
• Hemoglobin \>= 8.0 g/dl (within 2 weeks prior to registration); Note: The use of transfusion or other intervention to achieve Hgb \>= 8.0 g/dl is acceptable
• Serum creatinine \< 1.5 mg/dl or creatinine clearance (CC) \>= 50 ml/min determined by 24-hour collection or estimated by Cockcroft-Gault formula (within 2 weeks prior to registration)
• Bilirubin \< 2 mg/dl (within 2 weeks prior to registration)
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \< 3 x the upper limit of normal (within 2 weeks prior to registration)

You may not qualify if:

• Cancers of the oral cavity (oral tongue, floor mouth, alveolar ridge, buccal or lip), or the nasopharynx, hypopharynx, or larynx, even if p16 positive
• Carcinoma of the neck of unknown primary site origin (even if p16 positive)
• Definitive clinical or radiologic evidence of metastatic disease or adenopathy below the clavicles
• Gross total excision of both primary and nodal disease with curative intent; this includes tonsillectomy, local excision of primary site, and nodal excision that removes all clinically and radiographically evident disease
• Simultaneous primary cancers or separate bilateral primary tumor sites
• Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 1095 days (3 years) (for example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible)
• Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowable; patients who have received PD-1/PD-L1 or CTLA4 therapy for a previous malignancy are not eligible
• Prior RT to the region of the study cancer that would result in overlap of radiation therapy fields
• Severe, active co-morbidity defined as any of the following: Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months; acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration; chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days of registration; hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; a diagnosis of immunodeficiency or use of any form of systemic immunosuppressive therapy. The use of physiologic doses of corticosteroids may be approved after consultation with the sponsor
• Active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Steroid premedications for contrast allergy allowed
• Has evidence of active, non-infectious pneumonitis
• Has received a live vaccine within 30 days of planned start of study therapy
• History of severe hypersensitivity or contraindication to CT or PET contrast material uncontrolled with pre-medications (steroids, antihistamines)

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center Website

MeSH Terms

Conditions

Oropharyngeal Neoplasms; Squamous Cell Carcinoma of Head and Neck

Interventions

Radiotherapy, Intensity-Modulated; Ipilimumab; CTLA-4 Antigen; Nivolumab

Condition Hierarchy (Ancestors)

Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Neoplasms; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immune Checkpoint Proteins; Costimulatory and Inhibitory T-Cell Receptors; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Antigens, Differentiation, T-Lymphocyte; Antigens, Differentiation; Antigens, Surface; Antigens; Biological Factors; Biomarkers

Results Point of Contact

• Title: Dr. Renata Ferrarotto
• Organization: The University of Texas MD Anderson Cancer Center

rferrarotto@mdanderson.org

(713) 745-6774

Study Officials

• Renata Ferrarotto, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 13, 2018
• First Posted: January 10, 2019
• Study Start: July 25, 2019
• Primary Completion: July 25, 2025
• Study Completion: April 14, 2026
• Last Updated: April 30, 2026
• Results First Posted: March 17, 2026

Record last verified: 2026-04

Locations

US (1)