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

  • STATUS
    Recruiting
  • End date
    Feb 9, 2036
  • participants needed
    464
  • sponsor
    NRG Oncology
Updated on 12 May 2022

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.

Description

PRIMARY OBJECTIVES:

I. To determine whether radiation with low-dose cisplatin weekly is superior in terms of acute toxicity, as measured by the T-scores (TAME method), to radiation with high-dose cisplatin every 3 weeks for patients with locoregionally advanced squamous cell carcinoma of the head and neck (SCCHN). (Phase II) II. To determine whether radiation with low-dose cisplatin weekly is non-inferior to radiation with high-dose cisplatin every 3 weeks in terms of overall survival (OS) for patients with locoregionally advanced SCCHN. (Phase III) III. To determine whether radiation with low-dose cisplatin weekly is superior in terms of acute toxicity, as measured by the T-scores (TAME method), to radiation with high-dose cisplatin every 3 weeks for patients with locoregionally advanced SCCHN. (Phase III)

SECONDARY OBJECTIVES:

I. To assess and compare progression-free survival (PFS) between arms. II. To assess and compare locoregional failure and distant metastasis between arms .

III. To assess acute and late toxicity (Common Terminology Criteria for Adverse Events [CTCAE] version 5.0).

IV. To assess patient-reported outcomes quality of life (PRO/QOL), as measured by the Functional Assessment of Cancer Therapy-Head and Neck (FACT-H&N) (primary PRO), between arms.

V. To assess hearing loss, as measured by audiograms and the modified TUNE grading scale between arms.

VI. To assess hearing loss, as measured by speech audiometry Consonant-Nucleus-Consonant word scores and tympanometry (subject to the modified TUNE grading scale testing results; otherwise, it will be an exploratory objective).

VII. To assess hearing-related QOL as measured by the Hearing Handicap Inventory-Screening (HHIA-S) (secondary PRO), between arms.

EXPLORATORY OBJECTIVE:

I. To collect blood and tissue specimens for future translational science studies. For instance, to examine how germline and somatic genetic variants, such as TP53, CDKN2A, PIK3CA, PTEN, NFE2L2, and KEAP1, may influence cisplatin-related efficacy and toxicity, and to assess the effect of regular nonsteroidal anti-inflammatory drugs (NSAIDs) use and genomic activation of PIK3CA (mutation or amplification) or loss of PTEN, the negative regulator of PI3K, on disease-free survival or overall survival.

OUTLINE: Patients are assigned to 1 of 2 groups.

GROUP I (NON-OROPHARYNGEAL CANCER [OPC]/p16-NEGATIVE OPC): Patients are randomized to 1 of 2 arms.

ARM I: 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 intravenously (IV) once every 3 weeks (Q3W) (on days 1, 22, and 43) during radiation therapy in the absence of disease progression or unacceptable toxicity.

ARM II: 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 once a week (QW) during radiation therapy in the absence of disease progression or unacceptable toxicity.

GROUP II (p16-POSITIVE OPC/CANCER OF UNKNOWN PRIMARY [CUP]): Patients are randomized to 1 of 2 arms.

ARM III: 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.

ARM IV: 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.

After completion of study treatment, patients are followed up at 1 month, every 3 months during year 1-2, every 6 months during year 3-5, then annually thereafter.

Details
Condition 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
Treatment radiation therapy, questionnaire administration, cisplatin, quality-of-life assessment
Clinical Study IdentifierNCT05050162
SponsorNRG Oncology
Last Modified on12 May 2022

Eligibility

Yes No Not Sure

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
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
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