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Comparing weekly vs. every three weeks cisplatin with radiation for advanced head and neck cancer

Randomized Phase II/III Trial of Radiation With Cisplatin at 100 mg/m2 Every Three Weeks Versus Radiation With Weekly Cisplatin at 40 mg/m2 for Patients With Locoregionally Advanced Squamous Cell Carcinoma of the Head and Neck (SCCHN)

Phase2; Phase3 Interventional NRG Oncology · NCT05050162

This study is testing whether giving cisplatin weekly instead of every three weeks along with radiation can help people with advanced head and neck cancer feel better and live longer.

Quick facts

PhasePhase2; Phase3
Study typeInterventional
Enrollment1714 (estimated)
Ages18 Years and up
SexAll
SponsorNRG Oncology Academic / other
Drugs / interventionschemotherapy, radiation
Locations363 sites (Mobile, Alabama and 362 other locations)
Trial IDNCT05050162 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the effectiveness and tolerability of administering cisplatin weekly compared to every three weeks in conjunction with radiation therapy for patients with advanced head and neck cancer. The study aims to determine if the weekly regimen results in less acute toxicity and if it is non-inferior in terms of overall survival compared to the less frequent dosing. Additionally, the trial will assess progression-free survival, locoregional failure, and patient-reported quality of life outcomes. The research involves multiple medical centers and utilizes advanced imaging techniques to monitor patient responses.

Who should consider this trial

Good fit: Ideal candidates include patients with pathologically confirmed advanced squamous cell carcinoma of the head and neck, particularly those with p16-positive oropharyngeal cancer.

Not a fit: Patients with early-stage head and neck cancer or those not meeting the specific histological criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could lead to improved treatment tolerability and potentially better survival outcomes for patients with advanced head and neck cancer.

How similar studies have performed: Previous studies have shown promise in using different dosing schedules of cisplatin, but this specific comparison is novel.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* Pathologically (histologically or cytologically) proven diagnosis of SCCHN of the oropharynx, larynx, hypopharynx, or p16-positive unknown primary prior to registration; specimen from cervical lymph nodes with a well-defined primary site documented clinically or radiologically is acceptable; in patients with carcinoma of unknown primary this will be sufficient for pathologic confirmation without a clinically or radiographically defined primary site

  * For patients with oropharyngeal cancer (OPC)/cancer of unknown primary (CUP):

P16 status based on local site immunohistochemical tissue staining is required. A cell block obtained from a fine needle aspiration (FNA) biopsy specimen may be used as the sole diagnostic tissue. Centers are encouraged to contact the pathology chair for clarification.

* Note: Institutions must screen patients for p16 status by immunohistochemistry (IHC) in order to be eligible for the trial using a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory. A rigorous laboratory accreditation process similar to the United States (U.S.) CLIA certification, such as the provincial accreditation status offered by the Ontario Laboratory Accreditation (OLA) Program in Canada, the College of American Pathologists (CAP), or an equivalent accreditation in other countries, is acceptable.

  * The p16 results must be reported on the pathology report being submitted. The p16 positivity is defined as \> 70% of tumor cells showing strong nuclear and/or cytoplasmic immunostaining with p16 antibody.
  * For patients with laryngeal and hypopharyngeal primaries: Analysis of p16 status is NOT required.

    * Patients must have clinically or radiographically evident measurable disease at the primary site or at nodal stations. Simple tonsillectomy or local excision of the primary without removal of nodal disease is permitted, as is excision removing gross nodal disease but with intact primary site. Limited neck dissections retrieving =\< 4 nodes are permitted and considered as non-therapeutic nodal excisions
    * Clinical stage (American Joint Committee on Cancer \[AJCC\], 8th ed.), including no distant metastases based on the following diagnostic workup:
  * History/physical examination within 60 days prior to registration
  * One of the following imaging studies is required within 60 days prior to registration:
* Computed tomography (CT) scan of neck (diagnostic quality with contrast, unless contraindicated) OR
* Magnetic resonance imaging (MRI) of the neck (diagnostic quality with contrast, unless contraindicated) OR
* Fludeoxyglucose F-18 (FDG)-positron emission tomography (PET)/CT of the neck; the CT component must be of diagnostic quality with contrast, unless contraindicated.

  * Note: A diagnostic quality CT or MRI with contrast or FDG-PET/CT scan of neck performed for the purposes of radiation planning may serve as both staging and planning tools

    * One of the following imaging studies is required within 60 days prior to registration:
* FDG-PET/CT of the chest; FDG-PET/CT scan is strongly preferred and highly recommended to be used for eligibility OR
* Chest CT

  * Exam with laryngopharyngoscopy (mirror or in office direct procedure acceptable) within 70 days prior to registration;
* Eligibility by patient cohort;

  * Non-OPC/p16-negative OPC Cohort; Tumor Site: Larynx/Hypopharynx; Clinical Staging (AJCC, 8th ed.): T3-4 N0 or T1-4 N1-3 T2 N0 (hypopharynx only)
  * Tumor Site: p16-negative OPC; Clinical Staging (AJCC, 8th ed.): T2N1, T1-4 N2-3, or T3-4 N0-1
* p16-positive OPC/CUP Cohort;

  * Tumor Site: OPC; Smoking Status: =\< 10 pack-years; Clinical Staging (AJCC, 8th ed.): T1-3 N2-3 or T4 N0-3
  * Tumor Site: OPC; Smoking Status: \> 10 pack-years; Clinical Staging (AJCC, 8th ed.): T1N2-3, T2N1-3, or T3-4 N0-3
  * Tumor Site: CUP; Smoking Status: Any; Clinical Staging (AJCC, 8th ed.): T0 N2-3 Note: Cigar and pipe tobacco consumption is not included in calculating the lifetime pack-years. Marijuana consumption is likewise not considered in this calculation. There is also no clear scientific evidence regarding the role of chewing tobacco-containing products in oropharyngeal cancer, although this is possibly more concerning given the proximity of the oral cavity and oropharynx. In any case, investigators should not count use of non-cigarette tobacco products in the pack-years calculation.

    * Age \>= 18
    * Zubrod (Eastern Cooperative Oncology Group \[ECOG\]) performance status of 0-1 within 14 days prior to registration
    * Absolute neutrophil count (ANC) \>= 1,500 cells/mm\^3 (within 30 days prior to registration)
    * Platelets \>= 75,000 cells/mm\^3 (within 30 days prior to registration)
    * Hemoglobin \>= 8.0 g/dL (within 30 days prior to registration)

      * Note: The use of transfusion or other intervention to achieve hemoglobin \[Hgb\] \>= 8.0 g/dL is acceptable)
    * Calculated creatinine clearance (CrCl) \>= 50 mL/min by the Cockcroft-Gault formula (within 30 days prior to registration)
    * Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) (within 30 days prior to registration) (not applicable to patients with known Gilbert's syndrome)
    * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 1.5 x institutional ULN (within 30 days prior to registration)
    * Known human immunodeficiency virus (HIV) infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months and CD4 T Cell count \> 200 cells/mm\^3 are eligible for this trial. Testing is not required for entry into protocol
    * 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 eligible for this trial
    * Negative urine or serum pregnancy test (in persons of childbearing potential) within 14 days prior to registration. Childbearing potential is defined as any person who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes
    * Willing to use highly effective contraceptives for participants of childbearing potential (participants who may become pregnant or who may impregnate a partner) during therapy and for 14 months (females); for 11 months (males) following last dose of cisplatin; this inclusion is necessary because the treatment in this study may be significantly teratogenic.
    * The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information

Exclusion Criteria:

* Patients with oral cavity cancer, nasopharynx cancer, or p16-negative cancer of unknown primary (CUP)
* Recurrence of the study cancer
* Definitive clinical or radiologic evidence of distant metastatic disease
* Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowable, however, any prior exposure to cisplatin is excluded
* Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
* Severe, active co-morbidity defined as follows:

  * Unstable angina requiring hospitalization in the last 6 months
  * Myocardial infarction within the last 6 months
  * New York Heart Association Functional Classification III/IV (Note: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification.)
  * Persistent grade 3-4 (CTCAE version 5.0) electrolyte abnormalities that cannot be reversed despite replacement as indicated by repeat testing
  * Patient must not have an active infection requiring IV antibiotics prior to registration;
  * Other chronic renal disease like nephrotic syndrome, that could be worsened by cisplatin therapy
  * History of allogenic organ transplantation
  * Any symptomatic peripheral sensory neuropathy grade \>= 2 (CTCAE version 5.0);
* Pregnancy and individuals unwilling to discontinue nursing
* History of hypersensitivity to cisplatin or platinum-containing compounds

Where this trial is running

Mobile, Alabama and 362 other locations

+313 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Advanced Head and Neck Squamous Cell CarcinomaAdvanced Hypopharyngeal Squamous Cell CarcinomaAdvanced Laryngeal Squamous Cell CarcinomaAdvanced Oropharyngeal Squamous Cell CarcinomaClinical Stage III HPV-Mediated Oropharyngeal Carcinoma AJCC v8Clinical Stage IV HPV-Mediated Oropharyngeal Carcinoma AJCC v8Stage III Head and Neck Cutaneous Squamous Cell Carcinoma AJCC v8Stage III Oropharyngeal Carcinoma AJCC v8
Last reviewed 2026-06-09 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.