Nivolumab + Chemoradiation in Stage II-IVB Nasopharyngeal Carcinoma (NPC)

NCT03267498 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 162010NCI-2017-02291
• Study Type: interventional
• Target: 40
• Locations: 2 countries
• Sites: 2

Brief Summary

This phase II trial studies how well nivolumab and chemoradiotherapy works in treating patients with stage II-IVB nasopharyngeal cancer. Monoclonal antibodies, such as nivolumab, may block tumor growth in different ways by targeting certain cells. Chemoradiotherapy is the combination of chemotherapy and radiation therapy and may prevent the cancer from spreading when combined with nivolumab. Giving nivolumab and chemoradiotherapy may work better in treating patients with stage II-IVB nasopharyngeal cancer.

Conditions

Nasopharyngeal Carcinoma

Outcome Measures

Primary Outcomes (1)

• Rate of Completion of All Adjuvant Immunotherapy

  The rate of completion of all adjuvant therapy by patients treated at the maximum tolerated dose (MTD) schedule will be determined and compared to a historical control rate of 52%, the rate of completion of a standard adjuvant cisplatin-based platform to determine feasibility of study treatment

  Up to 1 year

Secondary Outcomes (7)

• Overall Response Rate (ORR)

  Up to 1 year after completion of treatment

• Number of Treatment-related Adverse Events (AEs)

  Up to 1 year after completion of treatment

• Mean Loco-regional Control (LRC) Rate

  Up to 1 year after completion of treatment

• Mean Distant Metastasis (DM) Rate

  Up to 1 year after completion of treatment

• Mean Change in Scores on the Functional Assessment of Cancer Therapy - Nasopharyngeal Cancer (FACT-NP)

  Up to 1 year after completion of treatment

Study Arms (1)

Nivolumab + chemoradiation

EXPERIMENTAL

Patients receive nivolumab IV over 60 minutes on day 1 of courses 1-5 and 7-12. Treatment repeats every 14 days for 11 courses in the absence of disease progression or unacceptable toxicity. Beginning at course 2, patients undergo radiation therapy QD 5 days per week and receive cisplatin IV over 30-60 minutes on day 1. Treatment repeats every 7 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.

Drug: Nivolumab; Drug: Cisplatin; Radiation: Radiation Therapy

Interventions

Nivolumab DRUG

Dosage 240mg of Nivolumab will be given intravenously over 60 minutes, every 14 days.

Also known as: Opdivo

Nivolumab + chemoradiation

Cisplatin DRUG

Dosage 40 mg/m2 of cisplatin will be given intravenously over 30-60 minutes, every 7 days.

Nivolumab + chemoradiation

Radiation Therapy RADIATION

2.12 Gy/fraction x 33 fractions of radiation therapy will be given, daily Monday - Friday

Nivolumab + chemoradiation

Eligibility Criteria

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

You may qualify if:

• Males and females ≥18 years of age.
• Histologically or cytologically confirmed nasopharyngeal carcinoma, stage II-IV by American Joint Committee on Cancer (AJCC) 7th edition, endemic-type (defined as World Health Organization (WHO) type 2a and 2b nonkeratinizing or undifferentiated subtypes, excluding WHO type I keratinizing subtype) performed on a biopsy that occurred within 90 days of registration.
• Positron emission tomography-computed tomography (PET-CT) (preferred) or a CT of chest, abdomen, and pelvis within 60 days of registration showing radiographic stage II to IVB nasopharyngeal cancer.
• No distant metastasis as verified by one of the study investigators.
• Documentation that the patient is a candidate for chemoradiation of their nasopharyngeal cancer by one of the study investigators.
• Ability to tolerate radiation therapy (e.g. lie flat and hold position for treatment).
• Measurable disease as defined by RECIST v1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Resolution of all acute toxic effects of any prior chemotherapy, radiotherapy or surgical procedures to NCI CTCAE Version 5.0 grade 1.
• Adequate hepatic, hematologic, and renal indices permitting administration of cisplatin and nivolumab (within 14 days of registration):
• Hepatic Function:
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × upper limit of normal (ULN); Total bilirubin ≤ 1.5 × ULN (except subjects with Gilbert Syndrome, who can have total bilirubin \< 3.0 mg/dL)
• Adequate bone marrow function:
• White blood cells (WBC) ≥ 2000/μL Neutrophils ≥ 1500/μL Platelet ≥ 100 x103/μL Hemoglobin \> 9.0 g/dL
• Adequate renal function:

You may not qualify if:

• Active second malignancy, i.e. patient known to have potentially fatal hematologic malignancy or another solid primary tumor present for which he/she may be (but not necessarily) currently receiving treatment. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are allowed to enroll in this trial. For example, patients with early-stage skin cancers, prostate cancer under surveillance with non-rising prostate-specific antigen (PSA), or meningioma or thyroid papillary cancers which are under surveillance are eligible. For determinations of a specific clinical condition, please consult with the Principal Investigator.
• Active, untreated central nervous system (CNS) metastases;
• Prior treatment with any other anti-programmed cell death protein-1 (anti-PD-1), or PD Ligand-1 (PD-L1) or PD Ligand-2 (PD-L2), anti-cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways, or cancer vaccine;
• Prior systemic cytotoxic therapy, antineoplastic biologic therapy, or major surgery within 28 days of first dose of study medication;
• Severe hypersensitivity reaction to treatment during prior administration of a monoclonal antibody (mAb) or history of allergy to any study drug component;
• Has received a live-virus vaccination within 30 days of planned treatment start;
• 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.
• Any evidence of current interstitial lung disease (ILD) or pneumonitis or a prior history of ILD or pneumonitis requiring oral or IV glucocorticoids;
• Active, known, or suspected autoimmune disease or any autoimmune condition that has required systemic treatment in the past 2 years (replacement therapies for hormone deficiencies are allowed); Subjects are permitted to enroll if they have 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.
• Clinically active diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction, or abdominal carcinomatosis (known risks factors for bowel perforation);
• Signs or symptoms of infection within 2 weeks prior to first day of study treatment.
• Patients with active tuberculosis (clinical evaluation in line with local practice), or a known history of active tuberculosis that in the opinion of the treating investigator has a high risk of reactivation.
• Received therapeutic oral or IV antibiotics within 2 weeks prior to first day of study treatment: Patients receiving prophylactic antibiotics (eg, to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible.
• Known positive test for human immunodeficiency virus (HIV);
• Known active hepatitis B or hepatitis C virus (HBV or HCV): Patients with past or resolved HBV infection (defined by a negative hepatitis B surface antigen (HBsAg) test and a positive anti-hepatitis B core antigen (HBc) (anti-HBc)antibody test) are eligible. HBV DNA must be obtained in these patients prior to first day of study treatment. Patients who have been recently discovered to have HBV with positive HBsAg test and positive anti-HBc antibody test but who have been started on antiretroviral treatment with nondetectable HBV DNA are eligible. HBV DNA must be obtained in these patients prior to first day of study treatment

Sponsors & Collaborators

• Sue Yom: lead
• National University of Singapore: collaborator
• Bristol-Myers Squibb: collaborator

Study Sites (2)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

National University Hospital Singapore

Singapore, 119074, Singapore

Location

MeSH Terms

Conditions

Nasopharyngeal Carcinoma

Interventions

Nivolumab; Cisplatin; Radiotherapy

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Therapeutics

Results Point of Contact

• Title: Dr. Sue Yom, MD PhD, MAS
• Organization: University of California, San Francisco

Sue.Yom@ucsf.edu

(415) 353-9893

Study Officials

• Sue S Yom, MD, PhD

  University of California, San Francisco

  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

Model Details: Single-arm, open label clinical trial of concurrent and adjuvant nivolumab, including a run-in phase to establish basic feasibility of the nivolumab schedule followed by expansion.

Study Record Dates

• First Submitted: August 23, 2017
• First Posted: August 30, 2017
• Study Start: February 14, 2018
• Primary Completion: October 31, 2024
• Study Completion: October 31, 2024
• Last Updated: January 12, 2026
• Results First Posted: January 12, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1); SG (1)