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Comparing High-Dose Cisplatin Every Three Weeks to Low-Dose Cisplatin Weekly When Combined With Radiation for Patients With Advanced Head and Neck Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05050162
Recruitment Status : Recruiting
First Posted : September 20, 2021
Last Update Posted : November 25, 2022
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
NRG Oncology

Brief Summary:
This phase II/III trial compares the effect of the combination of high-dose cisplatin every three weeks and radiation therapy versus low-dose cisplatin weekly and radiation therapy for the treatment of patients with locoregionally advanced head and neck cancer. Chemotherapy drugs, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. This study is being done to find out if low-dose cisplatin given weekly together with radiation therapy is the same or better than high-dose cisplatin given every 3 weeks together with radiation therapy in treating patients with head and neck cancer.

Condition or disease Intervention/treatment Phase
Advanced Head and Neck Squamous Cell Carcinoma Advanced Hypopharyngeal Squamous Cell Carcinoma Advanced Laryngeal Squamous Cell Carcinoma Advanced Oropharyngeal Squamous Cell Carcinoma Squamous Cell Carcinoma of Unknown Primary Drug: Cisplatin Other: Quality-of-Life Assessment Other: Questionnaire Administration Radiation: Radiation Therapy Phase 2 Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 464 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Randomized Phase II/III Trial of Radiation With High-Dose Cisplatin (100 mg/m2) Every Three Weeks Versus Radiation With Low-Dose Weekly Cisplatin (40 mg/m2) for Patients With Locoregionally Advanced Squamous Cell Carcinoma of the Head and Neck (SCCHN)
Actual Study Start Date : October 27, 2021
Estimated Primary Completion Date : February 9, 2031
Estimated Study Completion Date : February 9, 2036

Resource links provided by the National Library of Medicine

Drug Information available for: Cisplatin

Arm Intervention/treatment
Experimental: ARM I (high-dose cisplatin, radiation therapy)
NON-OPC/p16-NEGATIVE OPC: Patients undergo radiation therapy over 5 fractions a week for a total of 33-35 fractions in the absence of disease progression or unacceptable toxicity. Patients also receive high-dose cisplatin IV Q3W (on days 1, 22, and 43) during radiation therapy in the absence of disease progression or unacceptable toxicity.
Drug: Cisplatin
Given high-dose cisplatin IV
Other Names:
  • Abiplatin
  • Blastolem
  • Briplatin
  • CDDP
  • Cis-diammine-dichloroplatinum
  • Cis-diamminedichloridoplatinum
  • Cis-diamminedichloro Platinum (II)
  • Cis-diamminedichloroplatinum
  • Cis-dichloroammine Platinum (II)
  • Cis-platinous Diamine Dichloride
  • Cis-platinum
  • Cis-platinum II
  • Cis-platinum II Diamine Dichloride
  • Cismaplat
  • Cisplatina
  • Cisplatinum
  • Cisplatyl
  • Citoplatino
  • Citosin
  • Cysplatyna
  • DDP
  • Lederplatin
  • Metaplatin
  • Neoplatin
  • Peyrone's Chloride
  • Peyrone's Salt
  • Placis
  • Plastistil
  • Platamine
  • Platiblastin
  • Platiblastin-S
  • Platinex
  • Platinol
  • Platinol- AQ
  • Platinol-AQ
  • Platinol-AQ VHA Plus
  • Platinoxan
  • Platinum
  • Platinum Diamminodichloride
  • Platiran
  • Platistin
  • Platosin

Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

Other: Questionnaire Administration
Ancillary studies

Radiation: Radiation Therapy
Undergo radiation therapy
Other Names:
  • Cancer Radiotherapy
  • ENERGY_TYPE
  • Irradiate
  • Irradiated
  • Irradiation
  • Radiation
  • Radiation Therapy, NOS
  • Radiotherapeutics
  • Radiotherapy
  • RT
  • Therapy, Radiation

Experimental: Arm II (low-dose cisplatin, radiation therapy)
NON-OPC/p16-NEGATIVE OPC: Patients undergo radiation therapy over 5 fractions a week for a total of 33-35 fractions in the absence of disease progression or unacceptable toxicity. Patients also receive low-dose cisplatin IV QW during radiation therapy in the absence of disease progression or unacceptable toxicity.
Drug: Cisplatin
Given low-dose cisplatin IV
Other Names:
  • Abiplatin
  • Blastolem
  • Briplatin
  • CDDP
  • Cis-diammine-dichloroplatinum
  • Cis-diamminedichloridoplatinum
  • Cis-diamminedichloro Platinum (II)
  • Cis-diamminedichloroplatinum
  • Cis-dichloroammine Platinum (II)
  • Cis-platinous Diamine Dichloride
  • Cis-platinum
  • Cis-platinum II
  • Cis-platinum II Diamine Dichloride
  • Cismaplat
  • Cisplatina
  • Cisplatinum
  • Cisplatyl
  • Citoplatino
  • Citosin
  • Cysplatyna
  • DDP
  • Lederplatin
  • Metaplatin
  • Neoplatin
  • Peyrone's Chloride
  • Peyrone's Salt
  • Placis
  • Plastistil
  • Platamine
  • Platiblastin
  • Platiblastin-S
  • Platinex
  • Platinol
  • Platinol- AQ
  • Platinol-AQ
  • Platinol-AQ VHA Plus
  • Platinoxan
  • Platinum
  • Platinum Diamminodichloride
  • Platiran
  • Platistin
  • Platosin

Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

Other: Questionnaire Administration
Ancillary studies

Radiation: Radiation Therapy
Undergo radiation therapy
Other Names:
  • Cancer Radiotherapy
  • ENERGY_TYPE
  • Irradiate
  • Irradiated
  • Irradiation
  • Radiation
  • Radiation Therapy, NOS
  • Radiotherapeutics
  • Radiotherapy
  • RT
  • Therapy, Radiation

Experimental: Arm III (high-dose cisplatin, radiation therapy)
p16-POSITIVE OPC/CUP: Patients undergo radiation therapy over 5 fractions a week for a total of 33-35 fractions in the absence of disease progression or unacceptable toxicity. Patients also receive high-dose cisplatin IV Q3W (on days 1, 22, and 43) during radiation therapy in the absence of disease progression or unacceptable toxicity.
Drug: Cisplatin
Given high-dose cisplatin IV
Other Names:
  • Abiplatin
  • Blastolem
  • Briplatin
  • CDDP
  • Cis-diammine-dichloroplatinum
  • Cis-diamminedichloridoplatinum
  • Cis-diamminedichloro Platinum (II)
  • Cis-diamminedichloroplatinum
  • Cis-dichloroammine Platinum (II)
  • Cis-platinous Diamine Dichloride
  • Cis-platinum
  • Cis-platinum II
  • Cis-platinum II Diamine Dichloride
  • Cismaplat
  • Cisplatina
  • Cisplatinum
  • Cisplatyl
  • Citoplatino
  • Citosin
  • Cysplatyna
  • DDP
  • Lederplatin
  • Metaplatin
  • Neoplatin
  • Peyrone's Chloride
  • Peyrone's Salt
  • Placis
  • Plastistil
  • Platamine
  • Platiblastin
  • Platiblastin-S
  • Platinex
  • Platinol
  • Platinol- AQ
  • Platinol-AQ
  • Platinol-AQ VHA Plus
  • Platinoxan
  • Platinum
  • Platinum Diamminodichloride
  • Platiran
  • Platistin
  • Platosin

Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

Other: Questionnaire Administration
Ancillary studies

Radiation: Radiation Therapy
Undergo radiation therapy
Other Names:
  • Cancer Radiotherapy
  • ENERGY_TYPE
  • Irradiate
  • Irradiated
  • Irradiation
  • Radiation
  • Radiation Therapy, NOS
  • Radiotherapeutics
  • Radiotherapy
  • RT
  • Therapy, Radiation

Experimental: Arm IV (low-dose cisplatin, radiation therapy)
p16-POSITIVE OPC/CUP: Patients undergo radiation therapy over 5 fractions a week for a total of 33-35 fractions in the absence of disease progression or unacceptable toxicity. Patients also receive low-dose cisplatin IV QW during radiation therapy in the absence of disease progression or unacceptable toxicity.
Drug: Cisplatin
Given low-dose cisplatin IV
Other Names:
  • Abiplatin
  • Blastolem
  • Briplatin
  • CDDP
  • Cis-diammine-dichloroplatinum
  • Cis-diamminedichloridoplatinum
  • Cis-diamminedichloro Platinum (II)
  • Cis-diamminedichloroplatinum
  • Cis-dichloroammine Platinum (II)
  • Cis-platinous Diamine Dichloride
  • Cis-platinum
  • Cis-platinum II
  • Cis-platinum II Diamine Dichloride
  • Cismaplat
  • Cisplatina
  • Cisplatinum
  • Cisplatyl
  • Citoplatino
  • Citosin
  • Cysplatyna
  • DDP
  • Lederplatin
  • Metaplatin
  • Neoplatin
  • Peyrone's Chloride
  • Peyrone's Salt
  • Placis
  • Plastistil
  • Platamine
  • Platiblastin
  • Platiblastin-S
  • Platinex
  • Platinol
  • Platinol- AQ
  • Platinol-AQ
  • Platinol-AQ VHA Plus
  • Platinoxan
  • Platinum
  • Platinum Diamminodichloride
  • Platiran
  • Platistin
  • Platosin

Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

Other: Questionnaire Administration
Ancillary studies

Radiation: Radiation Therapy
Undergo radiation therapy
Other Names:
  • Cancer Radiotherapy
  • ENERGY_TYPE
  • Irradiate
  • Irradiated
  • Irradiation
  • Radiation
  • Radiation Therapy, NOS
  • Radiotherapeutics
  • Radiotherapy
  • RT
  • Therapy, Radiation




Primary Outcome Measures :
  1. Incidence of acute toxicity (Phase II) [ Time Frame: Up to 180 days post-treatment ]
    Measured by the T-scores.

  2. Overall Survival (OS) (Phase III) [ Time Frame: From randomization to death of any cause, assessed up to 9 years ]
    OS rates will be estimated using the Kaplan-Meier method.

  3. Incidence of acute toxicity (Phase III) [ Time Frame: Up to 180 days post-treatment ]
    Measured by the T-scores.


Secondary Outcome Measures :
  1. Locoregional Failure Rates [ Time Frame: Up to 9 years ]
  2. Progression-free survival (PFS) [ Time Frame: From randomization to locoregional failure, distant metastasis or death due to any cause, whichever occurs first, assessed up to 9 years ]
    PFS rates will be estimated using the Kaplan-Meier method and between-arm differences compared using the log-rank test with a two-sided alpha of 0.05 (Kaplan 1958).

  3. Incidence of acute toxicity [ Time Frame: Up to 180 days post-treatment ]
    Measured by Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0.

  4. Incidence of late toxicity [ Time Frame: Up to 9 years ]
    Measured by CTCAE v5.0.

  5. Hearing loss [ Time Frame: At 6 months post-radiation therapy ]
    Measured by Hearing Handicap Inventory for Adults-Screening.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 should 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.): T1-2 N2-3 or T3-4 N0-3
    • Tumor Site: CUP; Smoking Status: Any; Clinical Staging (AJCC, 8th ed.): T0 N2-3

      • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05050162


Locations
Show Show 223 study locations
Sponsors and Collaborators
NRG Oncology
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Paul M Harari NRG Oncology
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Responsible Party: NRG Oncology
ClinicalTrials.gov Identifier: NCT05050162    
Other Study ID Numbers: NRG-HN009
NCI-2021-08925 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
NRG-HN009 ( Other Identifier: NRG Oncology )
NRG-HN009 ( Other Identifier: CTEP )
U10CA180868 ( U.S. NIH Grant/Contract )
First Posted: September 20, 2021    Key Record Dates
Last Update Posted: November 25, 2022
Last Verified: November 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Squamous Cell
Squamous Cell Carcinoma of Head and Neck
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Head and Neck Neoplasms
Neoplasms by Site
Cisplatin
1,2-diaminocyclohexaneplatinum II citrate
Antineoplastic Agents