Palifermin in Lessening Oral Mucositis in Patients Undergoing Radiation Therapy and Chemotherapy for Locally Advanced Head and Neck Cancer
NCT ID: NCT00360971
Last Updated: 2017-12-26
Study Results
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View full resultsBasic Information
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TERMINATED
PHASE3
21 participants
INTERVENTIONAL
2006-07-31
2009-02-28
Brief Summary
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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.
Detailed Description
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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.
Conditions
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Keywords
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Study Design
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RANDOMIZED
PARALLEL
SUPPORTIVE_CARE
TRIPLE
Study Groups
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Palifermin
Concurrent radiation therapy, cisplatin, and palifermin followed by neck dissection for indicated patients.
palifermin
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.
cisplatin
Patients will receive cisplatin (100 mg/m2) administered intravenously on days 1, 22, and 43 of the treatment course.
neck dissection
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.
radiation therapy
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.
Placebo
Concurrent radiation therapy, cisplatin, and placebo followed by neck dissection for indicated patients.
cisplatin
Patients will receive cisplatin (100 mg/m2) administered intravenously on days 1, 22, and 43 of the treatment course.
placebo
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.
neck dissection
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.
radiation therapy
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.
Interventions
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palifermin
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.
cisplatin
Patients will receive cisplatin (100 mg/m2) administered intravenously on days 1, 22, and 43 of the treatment course.
placebo
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.
neck dissection
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.
radiation therapy
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.
Eligibility Criteria
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Inclusion Criteria
2. 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;
3. 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.
4. 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;
5. Zubrod Performance Status 0-1;
6. Age \> 18;
7. 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.)
8. Adequate hepatic function with bilirubin \< 1.5 mg/dl, AST or ALT \< 2 x ULN within 2 weeks prior to registration;
9. 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)
10. 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);
11. Serum pregnancy test for women of childbearing potential within 2 weeks prior to registration;
12. Women of childbearing potential and male participants must practice adequate contraception.
13. Patient agrees to refrain from using all products listed in Section 9.2, "Non-permitted Supportive Therapy";
14. Patient must sign study specific informed consent prior to study entry.
Exclusion Criteria
2. Stage IVC (AJCC, 6th edition) \[Any T, Any N, M1\] or distant metastases at protocol study entry; T1N1M0 patients are excluded.
3. Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years;
4. Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowable. See Sections 1 and 3.
5. Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields;
6. Initial surgical treatment, excluding diagnostic biopsy of the primary site or nodal sampling of neck disease; radical or modified neck dissection is not permitted.
7. 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.
8. Collagen vascular disease, such as scleroderma, as this disease is thought to predispose patients to increased risk for radiation-associated toxicities;
9. Previous treatment with palifermin or other keratinocyte growth factors, such as velafermin or repifermin;
10. 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®;
11. 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.
18 Years
ALL
No
Sponsors
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National Cancer Institute (NCI)
NIH
Radiation Therapy Oncology Group
NETWORK
Responsible Party
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Principal Investigators
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David I. Rosenthal, MD
Role: STUDY_CHAIR
M.D. Anderson Cancer Center
Locations
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Mayo Clinic Scottsdale
Scottsdale, Arizona, United States
Auburn Radiation Oncology
Auburn, California, United States
Providence Saint Joseph Medical Center - Burbank
Burbank, California, United States
Radiation Oncology Centers - Cameron Park
Cameron Park, California, United States
Mercy Cancer Center at Mercy San Juan Medical Center
Carmichael, California, United States
Enloe Cancer Center at Enloe Medical Center
Chico, California, United States
City of Hope Comprehensive Cancer Center
Duarte, California, United States
USC/Norris Comprehensive Cancer Center and Hospital
Los Angeles, California, United States
Radiation Oncology Center - Roseville
Roseville, California, United States
Radiological Associates of Sacramento Medical Group, Incorporated
Sacramento, California, United States
Mercy General Hospital
Sacramento, California, United States
Torrance Memorial Medical Center
Torrance, California, United States
Solano Radiation Oncology Center
Vacaville, California, United States
CCOP - Christiana Care Health Services
Newark, Delaware, United States
Saint John's Cancer Center at Saint John's Medical Center
Anderson, Indiana, United States
St. Agnes Hospital Cancer Center
Baltimore, Maryland, United States
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States
Dickinson County Healthcare System
Iron Mountain, Michigan, United States
Borgess Medical Center
Kalamazoo, Michigan, United States
West Michigan Cancer Center
Kalamazoo, Michigan, United States
Bronson Methodist Hospital
Kalamazoo, Michigan, United States
William Beaumont Hospital - Royal Oak Campus
Royal Oak, Michigan, United States
Mayo Clinic Cancer Center
Rochester, Minnesota, United States
CentraCare Clinic - River Campus
Saint Cloud, Minnesota, United States
Regional Cancer Center at Singing River Hospital
Pascagoula, Mississippi, United States
Great Falls Clinic - Main Facility
Great Falls, Montana, United States
Cancer Institute of New Jersey at Cooper University Hospital - Camden
Camden, New Jersey, United States
Franklin & Edith Scarpa Regional Cancer Center at South Jersey Healthcare
Vineland, New Jersey, United States
Cancer Institute of New Jersey at Cooper - Voorhees
Voorhees Township, New Jersey, United States
Duke Comprehensive Cancer Center
Durham, North Carolina, United States
Leo W. Jenkins Cancer Center at ECU Medical School
Greenville, North Carolina, United States
McDowell Cancer Center at Akron General Medical Center
Akron, Ohio, United States
Summa Center for Cancer Care at Akron City Hospital
Akron, Ohio, United States
Cancer Research UK Medical Oncology Unit at Churchill Hospital & Weatherall Institute of Molecular Medicine - Oxford
Salem, Ohio, United States
Cancer Treatment Center
Wooster, Ohio, United States
Oklahoma University Cancer Institute
Oklahoma City, Oklahoma, United States
Sharon Regional Cancer Care Center- Hermitage
Hermitage, Pennsylvania, United States
Intercommunity Cancer Center
Monroeville, Pennsylvania, United States
Alle-Kiski Medical Center
Natrona Heights, Pennsylvania, United States
Allegheny Cancer Center at Allegheny General Hospital
Pittsburgh, Pennsylvania, United States
Somerset Oncology Center
Somerset, Pennsylvania, United States
Mount Nittany Medical Center
State College, Pennsylvania, United States
Johnson City Medical Center Hospital
Johnson City, Tennessee, United States
M. D. Anderson Cancer Center at University of Texas
Houston, Texas, United States
Schiffler Cancer Center at Wheeling Hospital
Wheeling, West Virginia, United States
St. Vincent Hospital Regional Cancer Center
Green Bay, Wisconsin, United States
Bay Area Cancer Care Center at Bay Area Medical Center
Marinette, Wisconsin, United States
Cross Cancer Institute at University of Alberta
Edmonton, Alberta, Canada
Countries
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Other Identifiers
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CDR0000491088
Identifier Type: -
Identifier Source: secondary_id
RTOG-0435
Identifier Type: -
Identifier Source: org_study_id