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)
Overview
- Phase
- Phase 2
- Intervention
- Questionnaire Administration
- Conditions
- Not specified
- Sponsor
- NRG Oncology
- Enrollment
- 1714
- Locations
- 702
- Primary Endpoint
- Incidence of acute toxicity (Phase II)
- Status
- Suspended
- Last Updated
- 29 days ago
Overview
Brief Summary
This phase II/III trial compares whether cisplatin given weekly with radiation therapy is better tolerated than cisplatin given every three weeks with radiation therapy for the treatment of head and neck cancer that has spread to other places in the body (advanced). The second part of this study will also help to find out if the cisplatin given weekly approach will extend patients' life by at least the same amount of time as the cisplatin given every three weeks approach. Cisplatin is in a class of medications known as platinum-containing compounds that work by killing, stopping or slowing the growth of cancer cells. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Radiation with low-dose cisplatin given weekly may be effective in shrinking or stabilizing head and neck cancer or preventing its recurrence.
Detailed Description
PRIMARY OBJECTIVES: I. To determine whether radiation with cisplatin weekly is superior in terms of acute toxicity, as measured by the T-scores (TAME method), to radiation with 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 cisplatin weekly is non-inferior to radiation with cisplatin every 3 weeks in terms of overall survival (OS) for patients with locoregionally advanced SCCHN. (Phase III) III. To determine whether radiation with cisplatin weekly is superior in terms of acute toxicity, as measured by the T-scores (TAME method), to radiation with 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. VIII. To assess long-term PFS, OS, and toxicity between arms. IX. To assess 3-year restricted-mean survival time for OS and PFS between arms (if long-term update is warranted). 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 arms. ARM I (NON-OROPHARYNGEAL CANCER \[OPC\]/p16-NEGATIVE OPC group and p16-NEGATIVE OPC/CANCER OF UNKNOWN PRIMARY \[CUP\] group): 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 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 (NON-OROPHARYNGEAL CANCER \[OPC\]/p16-NEGATIVE OPC group and p16-NEGATIVE OPC/CANCER OF UNKNOWN PRIMARY \[CUP\] group): 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 cisplatin IV once a week (QW) for 7 weeks during radiation therapy in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) scan, or magnetic resonance imaging (MRI) or position emission tomography (PET) scan throughout the study.
Investigators
Eligibility 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:
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
Arms & Interventions
ARM I (radiation therapy, every 3 week cisplatin)
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 cisplatin IV once Q3W (on days 1, 22, and 43) during radiation therapy in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, or MRI or PET scan throughout the study.
Intervention: Questionnaire Administration
ARM I (radiation therapy, every 3 week cisplatin)
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 cisplatin IV once Q3W (on days 1, 22, and 43) during radiation therapy in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, or MRI or PET scan throughout the study.
Intervention: Radiation Therapy
ARM I (radiation therapy, every 3 week cisplatin)
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 cisplatin IV once Q3W (on days 1, 22, and 43) during radiation therapy in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, or MRI or PET scan throughout the study.
Intervention: Cisplatin
ARM I (radiation therapy, every 3 week cisplatin)
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 cisplatin IV once Q3W (on days 1, 22, and 43) during radiation therapy in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, or MRI or PET scan throughout the study.
Intervention: Computed Tomography
ARM I (radiation therapy, every 3 week cisplatin)
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 cisplatin IV once Q3W (on days 1, 22, and 43) during radiation therapy in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, or MRI or PET scan throughout the study.
Intervention: Magnetic Resonance Imaging
ARM I (radiation therapy, every 3 week cisplatin)
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 cisplatin IV once Q3W (on days 1, 22, and 43) during radiation therapy in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, or MRI or PET scan throughout the study.
Intervention: Positron Emission Tomography
ARM I (radiation therapy, every 3 week cisplatin)
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 cisplatin IV once Q3W (on days 1, 22, and 43) during radiation therapy in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, or MRI or PET scan throughout the study.
Intervention: Quality-of-Life Assessment
Arm II (radiation therapy, weekly cisplatin)
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 weekly cisplatin IV QW for 7 weeks during radiation therapy in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, or MRI or PET scan throughout the study.
Intervention: Computed Tomography
Arm II (radiation therapy, weekly cisplatin)
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 weekly cisplatin IV QW for 7 weeks during radiation therapy in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, or MRI or PET scan throughout the study.
Intervention: Magnetic Resonance Imaging
Arm II (radiation therapy, weekly cisplatin)
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 weekly cisplatin IV QW for 7 weeks during radiation therapy in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, or MRI or PET scan throughout the study.
Intervention: Positron Emission Tomography
Arm II (radiation therapy, weekly cisplatin)
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 weekly cisplatin IV QW for 7 weeks during radiation therapy in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, or MRI or PET scan throughout the study.
Intervention: Quality-of-Life Assessment
Arm II (radiation therapy, weekly cisplatin)
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 weekly cisplatin IV QW for 7 weeks during radiation therapy in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, or MRI or PET scan throughout the study.
Intervention: Questionnaire Administration
Arm II (radiation therapy, weekly cisplatin)
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 weekly cisplatin IV QW for 7 weeks during radiation therapy in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, or MRI or PET scan throughout the study.
Intervention: Radiation Therapy
Arm II (radiation therapy, weekly cisplatin)
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 weekly cisplatin IV QW for 7 weeks during radiation therapy in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, or MRI or PET scan throughout the study.
Intervention: Cisplatin
Outcomes
Primary Outcomes
Incidence of acute toxicity (Phase II)
Time Frame: Up to 180 days post-treatment
Measured by the T-scores.
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.
Incidence of acute toxicity (Phase III)
Time Frame: Up to 180 days post-treatment
Measured by the T-scores.
Secondary Outcomes
- Locoregional failure rates(Up to 9 years)
- Distant metastasis(Up to 9 years)
- Progression-free survival (PFS)(From randomization to locoregional failure, distant metastasis, or death due to any cause, whichever occurs first, assessed up to 9 years)
- Restricted mean survival time (RMST) for OS(At 3 years)
- RMST for PFS(At 3 years)
- Incidence of acute toxicity(Up to 180 days post-treatment)
- Quality of life(At 6 months post-radiation therapy)
- Hearing loss(At 6 months post-radiation therapy)
- Hearing loss (cochleotoxicity)(At 6 months post-radiation therapy)
- Incidence of late toxicity(Up to 9 years)