Adjuvant De-Escalated Radiation + Adjuvant Nivolumab for Intermediate-High Risk P16+ Oropharynx Cancer

NCT03715946 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: HCC 18-034
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 3

Brief Summary

This clinical trial will evaluate a new combination of treatments for Oropharyngeal Squamous Cell cancers (OPSCC), and compare it to the current standard of care (concurrent, platinum-based chemoradiotherapy). Chemoradiotherapy is efficacious, but also associated with significant toxicities and is only suitable for patients with good performance status and without severe comorbidities. The purpose of this trial is to demonstrate equivalent oncologic outcome with fewer adverse effects and improved quality of life when compared to the standard of care.

Conditions

Carcinoma, Squamous Cell of Head and Neck; Oropharynx Squamous Cell Carcinoma

Keywords

Oropharynx Cancer; OPSCC; Nivolumab; Adjuvant therapy; De-Escalated Radiation; Squamous cell carcinoma; P16+; Head and Neck cancer; Oropharynx Squamous Cell Carcinoma; Carcinoma, Squamous Cell of Head and Neck; Transoral surgery; Radiotherapy

Outcome Measures

Primary Outcomes (3)

• One-year Progression-free Survival (PFS)

  The probability of PFS measured from of beginning of study treatment, without local, regional or distant disease recurrence (appearance of new metastatic lesions). Measurement/determination of disease progression (recurrence) by CT and MRI, Chest X-Ray (Lesions acceptable as measurable when clearly defined and surrounded by an aerated lung), Tumor Markers, Clinical Examination (Clinically detected lesions will only be considered measurable when they are superficial (e.g., skin nodules and palpable lymph nodes). For skin lesions, documentation by color photography, including a ruler to estimate size of the lesion, Cytology and Histology (Cytologic confirmation of the neoplastic nature of any effusion that appears or worsens during treatment is required when the measurable tumor has met response or stable disease criteria, Ultrasound (Ultrasound may be used only as an alternative to clinical measurements for superficial palpable lymph nodes, subcutaneous lesions and thyroid nodules.

  At 1 year post start of treatment

• Two-year Progression-free Survival (PFS)

  The probability of PFS measured from of beginning of study treatment, without local, regional or distant disease recurrence (appearance of new metastatic lesions). Measurement/determination of disease progression (recurrence) by CT and MRI, Chest X-Ray (Lesions acceptable as measurable when clearly defined and surrounded by an aerated lung), Tumor Markers, Clinical Examination (Clinically detected lesions will only be considered measurable when they are superficial (e.g., skin nodules and palpable lymph nodes). For skin lesions, documentation by color photography, including a ruler to estimate size of the lesion, Cytology and Histology (Cytologic confirmation of the neoplastic nature of any effusion that appears or worsens during treatment is required when the measurable tumor has met response or stable disease criteria, Ultrasound (Ultrasound may be used only as an alternative to clinical measurements for superficial palpable lymph nodes, subcutaneous lesions and thyroid nodules.

  At 2 years post start of treatment

• PEG Tube Dependence

  Presence /absence of enteral feeding tube.

  At 1-year post-surgery

Secondary Outcomes (61)

• Worst Grade of Adverse Events Related to Treatment

  Up to 24 months

• Local Recurrence-free Survival (RFS) at One Year

  At 1-year post-surgery

• Local Recurrence-free Survival (RFS) at Two Years

  At 2-years post-surgery

• Regional Recurrence-free Survival (RFS)

  At one year post surgery

• Regional Recurrence-free Survival (RFS)

  At two years post-surgery

Other Outcomes (5)

• Tumor TP53 Mutation

  At baseline prior to treatment; Up to 5 years

• Determination of Tumor Genomics

  At baseline prior to treatment; Up to 5 years

• Presence of Plasma Cytokines

  At baseline prior to treatment; Up to 5 years

Study Arms (1)

Radiotherapy (RT) + Nivolumab Injection

EXPERIMENTAL

RT of 45 or 50 Gy in 25 daily fractions, 6 fractions per week. Nivolumab will be administered at 240 mg every 2 weeks during radiotherapy, and at 480 mg every 4 weeks for 6 doses after radiotherapy.

Drug: Nivolumab Injection; Radiation: Radiotherapy (RT)

Interventions

Nivolumab Injection DRUG

A fully human anti-programmed death 1 (PD-1) monoclonal antibody

Also known as: BMS-936558

Radiotherapy (RT) + Nivolumab Injection

Radiotherapy (RT) RADIATION

45-50 Gy accelerated fractionation in 25 daily fractions, 6 fractions per week

Radiotherapy (RT) + Nivolumab Injection

Eligibility Criteria

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

You may qualify if:

• Age \>/= 18 years.
• ECOG performance status of 0 or 1.
• Patients must have newly diagnosed, histologically or cytologically confirmed squamous cell carcinoma or undifferentiated carcinoma of the oropharynx. Patients must have been determined to have resectable oropharyngeal disease. Patients with primary tumor or nodal metastasis fixed to the carotid artery, skull base or cervical spine are not eligible.
• Patients must have intermediate risk factors, as described below as determined by imaging studies (performed \< 45 days prior to registration) and complete neck exam, from the skull base to the clavicles. The following imaging is required: CT scan of neck only with IV contrast or MRI. PET scan of HN and chest with IV contrasted CT correlation is encouraged prior to enrollment.
• Intermediate risk features: Tobacco \<10 pk-yr: T0-3 plus any one of the following: \>N2b (\> 5 LN's +), N2c/N3, +ENE \>1 mm, or + margin (if approved by surgical chair) OR Tobacco \>10 pk-yr: T0-3 plus any one of the following: any N2, N3, +ENE \>1 mm, or + margin (if approved by surgical chair)
• Patients must have no evidence of distant metastases (M0)
• Patients must have biopsy-proven p16+ oropharynx cancer; the histologic evidence of invasive squamous cell carcinoma may have been obtained from the primary tumor or metastatic lymph node. It is required that patients have a positive p16 IHC (as surrogate for HPV) status from either the primary tumor or metastatic lymph node.
• Carcinoma of the oropharynx associated with HPV as determined by p16 protein expression using immunohistochemistry (IHC) performed by a CLIA approved laboratory.
• No prior radiation above the clavicles.
• Patients with a history of a curatively treated malignancy must be disease-free for at least two years except for carcinoma in situ of cervix, differentiated thyroid cancer, melanoma in-situ (if fully resected), and/or non-melanomatous skin cancer, or clinically negligible in judgement of investigator.
• Patients with the following within the last 6 months prior to registration must be evaluated by a cardiologist and / or neurologist prior to entry into the study.
• Congestive heart failure \> NYHA Class II
• CVA / TIA
• Unstable angina
• Myocardial infarction (with or without ST elevation)

You may not qualify if:

• Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results.
• Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
• Subjects with a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
• 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 immune checkpoint pathways.
• Treatment with any chemotherapy, radiation therapy, biologics for cancer, or investigational therapy within 30 days of first administration of study treatment (subjects with prior radiation, cytotoxic or investigational products \< 4 weeks prior to treatment might be eligible after discussion between investigator and sponsor, if toxicities from the prior treatment have been resolved to Grade 1 (NCI CTCAE version 4).
• Known positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection. Subjects who test positive for HCV antibody but negative for HCV ribonucleic acid are permitted to enroll.
• Known history of testing positive for human immunodeficiency virus (HIV) and CD4 count \< 200 or known acquired immunodeficiency syndrome (AIDS).
• Any Grade 4 laboratory abnormalities.
• History of allergy to study drug components.
• History of severe hypersensitivity reaction to any human monoclonal antibody.
• Prisoners or subjects who are involuntarily incarcerated.
• Subjects compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness.

Sponsors & Collaborators

• Robert L. Ferris, MD, PhD: lead
• Bristol-Myers Squibb: collaborator

Study Sites (3)

Winship Cancer Institute @ Emory University Hospital Midtown

Atlanta, Georgia, 30308, United States

Location

Providence Cancer Institute

Portland, Oregon, 97213, United States

Location

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Oropharyngeal Neoplasms; Carcinoma, Squamous Cell; Head and Neck Neoplasms

Interventions

Nivolumab; Radiotherapy

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Therapeutics

Results Point of Contact

• Title: Barbara Stadterman, MPH
• Organization: UPMC Hillman Cancer Center

stadtermanbm@upmc.edu

4126475554

Study Officials

• Robert Ferris, MD, PhD

  UPMC Hillman 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 INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 19, 2018
• First Posted: October 23, 2018
• Study Start: November 16, 2018
• Primary Completion: March 31, 2023
• Study Completion: March 31, 2024
• Last Updated: January 13, 2025
• Results First Posted: January 13, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)