- ICH GCP
- Rejestr badań klinicznych w USA
- Badanie kliniczne NCT00360971
Palifermin in Lessening Oral Mucositis in Patients Undergoing Radiation Therapy and Chemotherapy for Locally Advanced Head and Neck Cancer
A Randomized, Phase III, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Palifermin (NSC# 740548; IND # 6370) for the Reduction of Oral Mucositis in Patients With Locally Advanced Head and Neck Cancer Receiving Radiation Therapy With Concurrent Chemotherapy (Followed by Surgery for Selected Patients)
RATIONALE: Growth factors, such as palifermin, may lessen the severity of mucositis, or mouth sores, in patients receiving radiation therapy and chemotherapy for head and neck cancer. It is not yet known whether palifermin is more effective than a placebo in lessening mucositis in patients receiving radiation therapy and chemotherapy for head and neck cancer.
PURPOSE: This randomized phase III trial is studying palifermin to see how well it works compared to a placebo in lessening oral mucositis in patients undergoing radiation therapy and chemotherapy for locally advanced head and neck cancer.
Przegląd badań
Status
Szczegółowy opis
OBJECTIVES:
Primary
- Compare the efficacy of palifermin vs placebo, in terms of burden of acute mucositis (defined to be 105 days [15 weeks] or less from the start of treatment), in patients with squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx undergoing concurrent radiotherapy and chemotherapy.
Secondary
- Compare incidence and time to onset of Grades 3 or 4 oral mucositis in patients treated with these regimens.
- Compare overall and progression-free survival and time to second primary in patients treated with these regimens.
OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to disease stage (III vs IVA or IVB), tumor site (oral cavity or oropharynx vs hypopharynx or larynx), and radiotherapy technique used on study (intensity-modulated radiotherapy [IMRT] vs 3-dimensional conformal radiotherapy [3D-CRT]). Patients are randomized to 1 of 2 treatment arms.
Mucositis, pain, and symptom burden are assessed at baseline, during radiotherapy, and post radiotherapy. Xerostomia is assessed at baseline, during radiotherapy, and several times after completion of study therapy.
After completion of study therapy, patients are followed periodically for 10 years.
PROJECTED ACCRUAL: A total of 298 patients will be accrued for this study.
Typ studiów
Zapisy (Rzeczywisty)
Faza
- Faza 3
Kontakty i lokalizacje
Lokalizacje studiów
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Alberta
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Edmonton, Alberta, Kanada, T6G 1Z2
- Cross Cancer Institute at University of Alberta
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Arizona
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Scottsdale, Arizona, Stany Zjednoczone, 85259-5499
- Mayo Clinic Scottsdale
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California
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Auburn, California, Stany Zjednoczone, 95603
- Auburn Radiation Oncology
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Burbank, California, Stany Zjednoczone, 91505
- Providence Saint Joseph Medical Center - Burbank
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Cameron Park, California, Stany Zjednoczone, 95682
- Radiation Oncology Centers - Cameron Park
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Carmichael, California, Stany Zjednoczone, 95608
- Mercy Cancer Center at Mercy San Juan Medical Center
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Chico, California, Stany Zjednoczone, 95926
- Enloe Cancer Center at Enloe Medical Center
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Duarte, California, Stany Zjednoczone, 91010-3000
- City of Hope Comprehensive Cancer Center
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Los Angeles, California, Stany Zjednoczone, 90089-9181
- USC/Norris Comprehensive Cancer Center and Hospital
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Roseville, California, Stany Zjednoczone, 95661
- Radiation Oncology Center - Roseville
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Sacramento, California, Stany Zjednoczone, 95815
- Radiological Associates of Sacramento Medical Group, Incorporated
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Sacramento, California, Stany Zjednoczone, 95819
- Mercy General Hospital
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Torrance, California, Stany Zjednoczone, 90509
- Torrance Memorial Medical Center
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Vacaville, California, Stany Zjednoczone, 95687
- Solano Radiation Oncology Center
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Delaware
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Newark, Delaware, Stany Zjednoczone, 19713
- CCOP - Christiana Care Health Services
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Indiana
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Anderson, Indiana, Stany Zjednoczone, 46016
- Saint John's Cancer Center at Saint John's Medical Center
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Maryland
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Baltimore, Maryland, Stany Zjednoczone, 21229
- St. Agnes Hospital Cancer Center
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Michigan
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Detroit, Michigan, Stany Zjednoczone, 48201-1379
- Barbara Ann Karmanos Cancer Institute
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Iron Mountain, Michigan, Stany Zjednoczone, 49801
- Dickinson County Healthcare System
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Kalamazoo, Michigan, Stany Zjednoczone, 49007
- Bronson Methodist Hospital
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Kalamazoo, Michigan, Stany Zjednoczone, 49001
- Borgess Medical Center
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Kalamazoo, Michigan, Stany Zjednoczone, 49007-3731
- West Michigan Cancer Center
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Royal Oak, Michigan, Stany Zjednoczone, 48073
- William Beaumont Hospital - Royal Oak Campus
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Minnesota
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Rochester, Minnesota, Stany Zjednoczone, 55905
- Mayo Clinic Cancer Center
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Saint Cloud, Minnesota, Stany Zjednoczone, 56303
- CentraCare Clinic - River Campus
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Mississippi
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Pascagoula, Mississippi, Stany Zjednoczone, 39581
- Regional Cancer Center at Singing River Hospital
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Montana
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Great Falls, Montana, Stany Zjednoczone, 59405
- Great Falls Clinic - Main Facility
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New Jersey
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Camden, New Jersey, Stany Zjednoczone, 08103
- Cancer Institute of New Jersey at Cooper University Hospital - Camden
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Vineland, New Jersey, Stany Zjednoczone, 08360
- Franklin & Edith Scarpa Regional Cancer Center at South Jersey Healthcare
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Voorhees, New Jersey, Stany Zjednoczone, 08043
- Cancer Institute of New Jersey at Cooper - Voorhees
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North Carolina
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Durham, North Carolina, Stany Zjednoczone, 27710
- Duke Comprehensive Cancer Center
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Greenville, North Carolina, Stany Zjednoczone, 27835-6028
- Leo W. Jenkins Cancer Center at ECU Medical School
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Ohio
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Akron, Ohio, Stany Zjednoczone, 44307
- McDowell Cancer Center at Akron General Medical Center
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Akron, Ohio, Stany Zjednoczone, 44309-2090
- Summa Center for Cancer Care at Akron City Hospital
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Salem, Ohio, Stany Zjednoczone, 44460
- Cancer Research UK Medical Oncology Unit at Churchill Hospital & Weatherall Institute of Molecular Medicine - Oxford
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Wooster, Ohio, Stany Zjednoczone, 44691
- Cancer Treatment Center
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Oklahoma
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Oklahoma City, Oklahoma, Stany Zjednoczone, 73104
- Oklahoma University Cancer Institute
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Pennsylvania
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Hermitage, Pennsylvania, Stany Zjednoczone, 16148
- Sharon Regional Cancer Care Center- Hermitage
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Monroeville, Pennsylvania, Stany Zjednoczone, 15146
- Intercommunity Cancer Center
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Natrona Heights, Pennsylvania, Stany Zjednoczone, 15065
- Alle-Kiski Medical Center
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Pittsburgh, Pennsylvania, Stany Zjednoczone, 15212
- Allegheny Cancer Center at Allegheny General Hospital
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Somerset, Pennsylvania, Stany Zjednoczone, 15501
- Somerset Oncology Center
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State College, Pennsylvania, Stany Zjednoczone, 16803
- Mount Nittany Medical Center
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Tennessee
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Johnson City, Tennessee, Stany Zjednoczone, 37604
- Johnson City Medical Center Hospital
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Texas
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Houston, Texas, Stany Zjednoczone, 77030-4009
- M. D. Anderson Cancer Center at University of Texas
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West Virginia
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Wheeling, West Virginia, Stany Zjednoczone, 26003
- Schiffler Cancer Center at Wheeling Hospital
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Wisconsin
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Green Bay, Wisconsin, Stany Zjednoczone, 54307-3508
- St. Vincent Hospital Regional Cancer Center
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Marinette, Wisconsin, Stany Zjednoczone, 54143
- Bay Area Cancer Care Center at Bay Area Medical Center
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Kryteria uczestnictwa
Kryteria kwalifikacji
Wiek uprawniający do nauki
Akceptuje zdrowych ochotników
Płeć kwalifikująca się do nauki
Opis
Inclusion Criteria:
- Pathologically (histologically or cytologically) proven (from primary lesion and/or lymph nodes) diagnosis of squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx;
Patients must have at least 2 mucosal sites of the oral cavity/oropharynx mucosa assessable by visual transoral inspection that will receive at least 66 Gy;
-2.1 Patients with tumors of the larynx or hypolarynx are eligible only if it is anticipated that the 2 index sites in the oral cavity/oropharynx mucosa will receive at least 66 Gy;
- Patients must be able to be evaluated for the primary endpoint; therefore, patients must be able to eat at least soft solids and not require a feeding tube for nutrition or hydration at study entry.
Selected Stage III (excluding T1N1MO) or IVA-B (AJCC, 6th edition) at study entry, including no distant metastases, based upon the following minimum diagnostic workup:
- 4.1 History/physical examination, including documentation of tobacco/alcohol use and current medications (including opioids/dosing), within 8 weeks prior to registration;
- 4.2 Chest x-ray (or Chest CT scan) within 6 weeks prior to registration;
- 4.3 MRI or CT scan with contrast of tumor site within 6 weeks prior to registration;
- 4.4 Assessment of mucositis and xerostomia within 2 weeks prior to registration;
- Zubrod Performance Status 0-1;
- Age > 18;
Adequate bone marrow function, defined as follows:
- 7.1 Absolute neutrophil count (ANC) > 1,800 cells/mm3 based upon CBC/differential obtained within 2 weeks prior to registration on study
- 7.2 Platelets > 100,000 cells/mm3 based upon CBC/differential obtained within 2 weeks prior to registration on study
- 7.3 Hemoglobin > 8.0 g/dl based upon CBC/differential obtained within 2 weeks prior to registration on study (Note: The use of transfusion or other intervention to achieve Hgb > 8.0 g/dl is acceptable.)
- Adequate hepatic function with bilirubin < 1.5 mg/dl, AST or ALT < 2 x ULN within 2 weeks prior to registration;
Adequate renal function with serum creatinine < 1.5 mg/dl and creatinine clearance (CC) ≥ 50 ml/min within 2 weeks prior to registration determined by 24-hour collection or estimated by Cockcroft-Gault formula:
CCr male = [(140 - age) x (wt in kg)]/[(Serum Cr mg/dl) x (72)] CCr female = 0.85 x (CrCl male)
- Normal serum calcium or normal corrected serum calcium within 2 weeks prior to registration; formula for corrected calcium if albumin valued is below normal range: Corrected calcium (mg/dl) = (4 - [patient's albumin (g/dl)] x 0.8) + patient's measured calcium (mg/dl);
- Serum pregnancy test for women of childbearing potential within 2 weeks prior to registration;
- Women of childbearing potential and male participants must practice adequate contraception.
- Patient agrees to refrain from using all products listed in Section 9.2, "Non-permitted Supportive Therapy";
- Patient must sign study specific informed consent prior to study entry.
Exclusion Criteria:
- Patients with a history of prior head and neck squamous cancer are ineligible;
- Stage IVC (AJCC, 6th edition) [Any T, Any N, M1] or distant metastases at protocol study entry; T1N1M0 patients are excluded.
- Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years;
- Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowable. See Sections 1 and 3.
- Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields;
- Initial surgical treatment, excluding diagnostic biopsy of the primary site or nodal sampling of neck disease; radical or modified neck dissection is not permitted.
Severe, active co-morbidity, defined as follows:
- 7.1 Symptomatic and/or uncontrolled cardiac disease, New York Heart Association Classification III or IV (see Appendix II);
- 7.2 Transmural myocardial infarction within the last 6 months;
- 7.3 Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration;
- 7.4 Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration.
- 7.5 Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects;
- 7.6 Patients known to be sero-positive for hepatitis B virus (HBV) or hepatitis C virus (HCV);
- 7.7 Patients known to be sero-positive for human immunodeficiency virus (HIV) or patients with Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition; note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with HIV or AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive.
- 7.8 A history of pancreatitis.
- Collagen vascular disease, such as scleroderma, as this disease is thought to predispose patients to increased risk for radiation-associated toxicities;
- Previous treatment with palifermin or other keratinocyte growth factors, such as velafermin or repifermin;
- Prior allergic reaction or known sensitivity to any of the agents administered during dosing, including E. coli-derived products, such as Nutropin®, Neupogen®, Humulin®, Roferon®; Neumega®, Neulasta®), IntronA®, Betaseron®;
- Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic.
Plan studiów
Jak projektuje się badanie?
Szczegóły projektu
- Główny cel: Leczenie podtrzymujące
- Przydział: Randomizowane
- Model interwencyjny: Przydział równoległy
- Maskowanie: Potroić
Broń i interwencje
Grupa uczestników / Arm |
Interwencja / Leczenie |
---|---|
Eksperymentalny: Palifermin
Concurrent radiation therapy, cisplatin, and palifermin followed by neck dissection for indicated patients.
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Four doses of palifermin, 180ųg/kg, administered as an i.v.
bolus injection over 30-60 seconds.
Starting on day -3 (Friday) prior to radiation therapy / chemotherapy and then once weekly, on days 5, 12, and 19.
Patients will receive cisplatin (100 mg/m2) administered intravenously on days 1, 22, and 43 of the treatment course.
A neck dissection is required for patients with persistent nodal disease, any stage, if a palpable abnormality or worrisome radiographic abnormality persists in the neck 8-9 weeks after completion of therapy.
A neck dissection is optional for patients with multiple positive lymph nodes or with lymph nodes exceeding 3 cm in diameter at pre-treatment (N2a, N2b, N3) who achieve a complete clinical and radiographic response in the neck.
All patients will be assessed at approximately 8 weeks post-treatment with CT scan or MRI by the same technique used at baseline.
A radiation dose of 70 Gy with at least 66 Gy to at least 2 mucosal sites of the oral cavity/oropharynx mucosa.
Radiation therapy can be given with 3D conformal (3D-CRT) or with intensity modulated RT (IMRT) techniques; however, the chosen modality must be used for the entire course of treatment.
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Komparator placebo: Placebo
Concurrent radiation therapy, cisplatin, and placebo followed by neck dissection for indicated patients.
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Patients will receive cisplatin (100 mg/m2) administered intravenously on days 1, 22, and 43 of the treatment course.
A neck dissection is required for patients with persistent nodal disease, any stage, if a palpable abnormality or worrisome radiographic abnormality persists in the neck 8-9 weeks after completion of therapy.
A neck dissection is optional for patients with multiple positive lymph nodes or with lymph nodes exceeding 3 cm in diameter at pre-treatment (N2a, N2b, N3) who achieve a complete clinical and radiographic response in the neck.
All patients will be assessed at approximately 8 weeks post-treatment with CT scan or MRI by the same technique used at baseline.
A radiation dose of 70 Gy with at least 66 Gy to at least 2 mucosal sites of the oral cavity/oropharynx mucosa.
Radiation therapy can be given with 3D conformal (3D-CRT) or with intensity modulated RT (IMRT) techniques; however, the chosen modality must be used for the entire course of treatment.
Four doses of placebo, 180ųg/kg, administered as an i.v.
bolus injection over 30-60 seconds.
Starting on day -3 (Friday) prior to radiation therapy / chemotherapy and then once weekly, on days 5, 12, and 19.
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Co mierzy badanie?
Podstawowe miary wyniku
Miara wyniku |
Opis środka |
Ramy czasowe |
---|---|---|
Duration of Oral Mucositis as Measured in Terms of Days
Ramy czasowe: Twice-weekly from start of treatment up to 15 weeks after the start of treatment.
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Duration in days of World Heath Organization (WHO) Grades 3 and 4 oral mucositis during the acute period (defined to be 105 days [15 weeks] or less from the start of treatment); duration is calculated from the onset of a Grade 3 or 4 oral mucositis to the day when an oral mucositis of ≤ Grade 2 is reported after the last oral mucositis of Grade 3 or 4. Patients with grade 0-2 mucositis have a duration of 0. This study required 298 patients to detect via two-sided t-test a reduction of mean duration of at least 9 days from 29 days (standard deviation = 23 days) on the placebo arm with 90% power and alpha = 0.05. Statistical testing was not done due to the small sample size. |
Twice-weekly from start of treatment up to 15 weeks after the start of treatment.
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Miary wyników drugorzędnych
Miara wyniku |
Opis środka |
Ramy czasowe |
---|---|---|
Number of Patients With Grade 3 or 4 Mucositis as Measured by the World Heath Organization (WHO) Scale
Ramy czasowe: Twice-weekly from start of treatment up to 15 weeks after the start of treatment.
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Adverse events are graded using CTCAE v3.0.
Grade refers to the severity of the AE.
The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE.
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Twice-weekly from start of treatment up to 15 weeks after the start of treatment.
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Time to Onset of Grade 3 or 4 Oral Mucositis as Measured by the World Heath Organization (WHO) Scale
Ramy czasowe: Twice-weekly from start of treatment up to 15 weeks after the start of treatment.
|
Adverse events are graded using CTCAE v3.0.
Grade refers to the severity of the AE.
The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE.
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Twice-weekly from start of treatment up to 15 weeks after the start of treatment.
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Overall Survival
Ramy czasowe: From randomization to maximum follow-up at time of analysis of 21 months
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An event is death from any cause.
Overall survival was not calculated due to the limited number of events.
Number of patients with an event is reported.
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From randomization to maximum follow-up at time of analysis of 21 months
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Progression-free Survival
Ramy czasowe: From randomization to maximum follow-up at time of analysis of 21 months
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An event is defined as the first occurrence of local, regional, distant disease.
Progression-free survival is calculated at the time from registration to the death of progression, death in the absence of progression, or last follow-up.
Progression-free survival was not calculated due to the limited number of events.
Number of patients with an event is reported.
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From randomization to maximum follow-up at time of analysis of 21 months
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Time to Second Primary Tumor
Ramy czasowe: From randomization to maximum follow-up at time of analysis of 21 months
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An event is occurrence of a second primary other than basal cell.
Time to second primary tumor was not calculated because there were no events.
Number of patients with an event is reported.
|
From randomization to maximum follow-up at time of analysis of 21 months
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Współpracownicy i badacze
Sponsor
Współpracownicy
Śledczy
- Krzesło do nauki: David I. Rosenthal, MD, M.D. Anderson Cancer Center
Daty zapisu na studia
Główne daty studiów
Rozpoczęcie studiów
Zakończenie podstawowe (Rzeczywisty)
Ukończenie studiów (Rzeczywisty)
Daty rejestracji na studia
Pierwszy przesłany
Pierwszy przesłany, który spełnia kryteria kontroli jakości
Pierwszy wysłany (Oszacować)
Aktualizacje rekordów badań
Ostatnia wysłana aktualizacja (Rzeczywisty)
Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości
Ostatnia weryfikacja
Więcej informacji
Terminy związane z tym badaniem
Słowa kluczowe
- Rak płaskonabłonkowy wargi i jamy ustnej w III stopniu zaawansowania
- Rak płaskonabłonkowy wargi i jamy ustnej IV stopnia
- rak płaskonabłonkowy jamy ustnej i gardła w III stopniu zaawansowania
- Rak płaskonabłonkowy jamy ustnej i gardła w IV stopniu zaawansowania
- rak płaskonabłonkowy gardła III stopnia
- rak płaskonabłonkowy gardła IV stopnia
- rak płaskonabłonkowy krtani w III stopniu zaawansowania
- Rak płaskonabłonkowy krtani w IV stopniu zaawansowania
- ból
- toksyczność promieniowania
- zapalenie błony śluzowej
Dodatkowe istotne warunki MeSH
Inne numery identyfikacyjne badania
- RTOG-0435
- CDR0000491088
Informacje o lekach i urządzeniach, dokumenty badawcze
Bada produkt leczniczy regulowany przez amerykańską FDA
Bada produkt urządzenia regulowany przez amerykańską FDA
produkt wyprodukowany i wyeksportowany z USA
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