Locoregionally advanced oropharyngeal cancer MedDRA version: 19.0 Level: PT Classification code 10031096 Term: Oropharyngeal cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Cisplatin
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Cisplatin
Other descriptive name: CISPLATIN
Concentration unit: mg/m2 milligram(s)/square meter
Sponsors
Irish Clinical Oncology Research Group CLG, trading as Cancer Trials Ireland
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: > Step 1: Registration 1. Pathologically (histologically/cytologically) proven diagnosis of squamous cell carcinoma (including the histological variants papillary squamous cell carcinoma&basaloid squamous cell carcinoma) of the oropharynx (tonsil, base of tongue, soft palate, or oropharyngeal walls); cytologic diagnosis from a cervical lymph node is sufficient in the presence of clinical evidence of a primary tumor in the oropharynx. Clinical evidence should be documented, may consist of palpation, imaging, or endoscopic evaluation&should be sufficient to estimate the size of the primary (for T stage). 2. Clinically or radiographically evident measurable disease at the primary site or at nodal stations. 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&considered as non-therapeutic nodal excisions. 3. Immunohistochemical (IHC) staining for p16 must be performed on tissue&this tissue must be submitted for central review. Fine needle aspiration (FNA) biopsy specimens may be used as the sole diagnostic tissue if formalin-fixed paraffin-embedded cell block material is available for p16 IHC. FNA specimens prepared with adequate p16 testing in this manner are acceptable to submit for central review. If the p16 preparation is not adequate, additional specimens will be required to establish p16 status. 4. Clinical stage T1-T2, N1-N2b or T3, N0-N2b (AJCC, 7th ed.) including no distant metastases based on the following diagnostic workup: ? General history&physical examination within 56 days prior to registration; ? Fiberoptic exam with laryngopharyngoscopy (mirror and/or fiberoptic and/or direct procedure) within 70 days prior to registration; ? One of the following combinations of imaging is required within 56 days prior to registration: a) A CT scan of the neck (with contrast) & a chest CT scan (with or without contrast); b) or an MRI of the neck (with contrast) & a chest CT scan (with or without contrast); c) or a CT scan of neck (with contrast) & a PET/CT of neck and chest (with or without contrast); d) or an MRI of the neck (with contrast) & a PET/CT of neck and chest (with or without contrast). Note: A CT scan of neck and/or a PET/CT performed for the purposes of radiation planning may serve as both staging&planning tools. 5. Patients must provide their personal smoking history prior to registration. The lifetime cumulative history cannot exceed 10 pack-years. Please refer to the protocol for details of pack-years calculation. 6. Zubrod Performance Status of 0-1 within 56 days prior to registration; 7. Age = 18; 8. The trial is open to both genders; 9. Adequate hematologic function within 14 days prior to registration, defined as follows: ? Absolute neutrophil count (ANC) = 1,500 cells/mm3; ? Platelets = 100,000 cells/mm3; ? Hemoglobin = 8.0 g/dl; Note: The use of transfusion or other intervention to achieve Hgb = 8.0 g/dl is acceptable. 10. Adequate renal function within 14 days prior to registration, defined as follows: ? Serum creatinine < 1.5 mg/dl or creatinine clearance (CC) = 50 ml/min determined by 24-hour collection or estimated by Cockcroft-Gault formula as described in protocol section 3.2.10. 11. Adequate hepatic function within 14 days prior to registration defined as follows: ? Bilirubin < 2 mg/d
Exclusion criteria
Exclusion criteria: > Step 1: Registration 1. Cancers considered to be from an oral cavity site (oral tongue, floor mouth, alveolar ridge, buccal or lip), or the nasopharynx, hypopharynx, or larynx, even if p16 positive, or histologies of adenosquamous, verrucous, or spindle cell carcinomas; 2. Carcinoma of the neck of unknown primary site origin (even if p16 positive); 3. Radiographically matted nodes, defined as 3 abutting nodes with loss of the intervening fat plane; 4. Supraclavicular nodes, defined as nodes visualized on the same axial imaging slice as the clavicle; 5. Definitive clinical or radiologic evidence of metastatic disease or adenopathy below the clavicles; 6. Gross total excision of both primary and nodal disease with curative intent; this includes tonsillectomy, local excision of primary site, and nodal excision that removes all clinically and radiographically evident disease. In other words, to participate in this protocol, the patient must have clinically or radiographically evident gross disease for which disease response can be assessed. 7. Patients with simultaneous primary cancers or separate bilateral primary tumor sites are excluded with the exception of patients with bilateral tonsil cancers; 8. Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 1095 days (3 years) (for example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible); 9. Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowable; 10. Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields; 11. Severe, active co-morbidity defined as follows: ? Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months; ? Transmural myocardial infarction within the last 6 months; ? Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration; ? Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days of registration; ? Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol other than those requested in protocol section 3.2.10. ? Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition with immune compromise greater than that noted in protocol section 3.1.13; note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive. Protocol-specific requirements may also exclude immuno-compromised patients. 12. Pregnancy; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic. 13. Prior allergic reaction to cisplatin.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary Objective: ? To select the arm(s) achieving a 2-year progression-free survival rate of = 85% without unacceptable swallowing toxicity at 1 year.;Secondary Objective: Secondary Objectives: ? To determine patterns of failure (locoregional relapse versus distant) and survival (overall and progression-free) at 6 months and 2 years; ? To determine acute toxicity profiles at the end of radiation therapy and at 1 and 6 months; ? To determine late toxicity profiles at 1 and 2 years; ? To determine patient-reported swallowing outcomes at 6 months and 1 and 2 years; ? To determine the predictive value of 12-14 week, post-treatment FDG-PET/CT for locoregional control and PFS at 2 years; ? To determine the predictive value of blood and tissue biomarkers for disease outcomes at 2 years; ? To determine swallowing recovery per videofluoroscopy imaging at 2 years.;Primary end point(s): Progression-free survival (PFS) at 2 years.;Timepoint(s) of evaluation of this end point: Progression free survival (PFS) is defined as from time of randomization to local-regional failure, distant metastasis or deaths due to any causes. PFS rates will be estimated for all treatment arms using the Kaplan-Meier method (1958).One sample binomial test will be used to test the 2-year PFS for each arm. Multivariate analysis will be performed using the Cox proportional hazards model. The interim analysis time will be 1.56 years from the start of study (6 months for site IRB approval,0.56 years for accrual,6-month follow up). Interim reports (containing information about accrual rate,pretreatment characteristics of patients accrued&the frequency&severity of adverse events) will be prepared biannually until the final analysis has been accepted for presentation or publication. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): ? Local-regional failure at 6 months and 2 years; ? Distant metastasis at 6 months and 2 years; ? Overall survival at 6 months and 2 years; ? Acute toxicities (= grade 3, CTCAE, v. 4) at the end of radiation therapy and at 1 and 6 months; ? Late toxicities at (= grade 3, CTCAE, v. 4) 1 and 2 years; ? Patient-reported swallowing outcomes at 6 months and 1 and 2 years; ? Post-treatment FDG-PET/CT; ? Translational research.;Timepoint(s) of evaluation of this end point: For the secondary endpoints listed in protocol section 13.2.2, OS rates will be estimated using the Kaplan-Meier method (1958) and the failure rates for the experimental treatment will be compared against the control using a log rank test. The cumulative incidence method will be used to estimate locoregional and distant failure rates and the failure rates for the experimental treatment will be compared against the control using a failure specific log rank test. Failure for local-regional failure and distant metastasis endpoints is defined in protocol section 13.6.1. | — |
Countries
Ireland, United States
Contacts
Public ContactClinical Program Leader
Irish Clinical Oncology Research Group CLG, trading as Cancer Trials Ireland
Outcome results
None listed