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Palifermin in Lessening Oral Mucositis in Patients Undergoing Radiation Therapy and Chemotherapy for Locally Advanced Head and Neck Cancer

2017년 11월 28일 업데이트: Radiation Therapy Oncology Group

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.

연구 개요

상태

종료됨

정황

개입 / 치료

상세 설명

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.

연구 유형

중재적

등록 (실제)

21

단계

  • 3단계

연락처 및 위치

이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.

연구 장소

  • 미국
    • Arizona
      • Scottsdale, Arizona, 미국, 85259-5499
        • Mayo Clinic Scottsdale
    • California
      • Auburn, California, 미국, 95603
        • Auburn Radiation Oncology
      • Burbank, California, 미국, 91505
        • Providence Saint Joseph Medical Center - Burbank
      • Cameron Park, California, 미국, 95682
        • Radiation Oncology Centers - Cameron Park
      • Carmichael, California, 미국, 95608
        • Mercy Cancer Center at Mercy San Juan Medical Center
      • Chico, California, 미국, 95926
        • Enloe Cancer Center at Enloe Medical Center
      • Duarte, California, 미국, 91010-3000
        • City of Hope Comprehensive Cancer Center
      • Los Angeles, California, 미국, 90089-9181
        • USC/Norris Comprehensive Cancer Center and Hospital
      • Roseville, California, 미국, 95661
        • Radiation Oncology Center - Roseville
      • Sacramento, California, 미국, 95815
        • Radiological Associates of Sacramento Medical Group, Incorporated
      • Sacramento, California, 미국, 95819
        • Mercy General Hospital
      • Torrance, California, 미국, 90509
        • Torrance Memorial Medical Center
      • Vacaville, California, 미국, 95687
        • Solano Radiation Oncology Center
    • Delaware
      • Newark, Delaware, 미국, 19713
        • CCOP - Christiana Care Health Services
    • Indiana
      • Anderson, Indiana, 미국, 46016
        • Saint John's Cancer Center at Saint John's Medical Center
    • Maryland
      • Baltimore, Maryland, 미국, 21229
        • St. Agnes Hospital Cancer Center
    • Michigan
      • Detroit, Michigan, 미국, 48201-1379
        • Barbara Ann Karmanos Cancer Institute
      • Iron Mountain, Michigan, 미국, 49801
        • Dickinson County Healthcare System
      • Kalamazoo, Michigan, 미국, 49007
        • Bronson Methodist Hospital
      • Kalamazoo, Michigan, 미국, 49001
        • Borgess Medical Center
      • Kalamazoo, Michigan, 미국, 49007-3731
        • West Michigan Cancer Center
      • Royal Oak, Michigan, 미국, 48073
        • William Beaumont Hospital - Royal Oak Campus
    • Minnesota
      • Rochester, Minnesota, 미국, 55905
        • Mayo Clinic Cancer Center
      • Saint Cloud, Minnesota, 미국, 56303
        • CentraCare Clinic - River Campus
    • Mississippi
      • Pascagoula, Mississippi, 미국, 39581
        • Regional Cancer Center at Singing River Hospital
    • Montana
      • Great Falls, Montana, 미국, 59405
        • Great Falls Clinic - Main Facility
    • New Jersey
      • Camden, New Jersey, 미국, 08103
        • Cancer Institute of New Jersey at Cooper University Hospital - Camden
      • Vineland, New Jersey, 미국, 08360
        • Franklin & Edith Scarpa Regional Cancer Center at South Jersey Healthcare
      • Voorhees, New Jersey, 미국, 08043
        • Cancer Institute of New Jersey at Cooper - Voorhees
    • North Carolina
      • Durham, North Carolina, 미국, 27710
        • Duke Comprehensive Cancer Center
      • Greenville, North Carolina, 미국, 27835-6028
        • Leo W. Jenkins Cancer Center at ECU Medical School
    • Ohio
      • Akron, Ohio, 미국, 44307
        • McDowell Cancer Center at Akron General Medical Center
      • Akron, Ohio, 미국, 44309-2090
        • Summa Center for Cancer Care at Akron City Hospital
      • Salem, Ohio, 미국, 44460
        • Cancer Research UK Medical Oncology Unit at Churchill Hospital & Weatherall Institute of Molecular Medicine - Oxford
      • Wooster, Ohio, 미국, 44691
        • Cancer Treatment Center
    • Oklahoma
      • Oklahoma City, Oklahoma, 미국, 73104
        • Oklahoma University Cancer Institute
    • Pennsylvania
      • Hermitage, Pennsylvania, 미국, 16148
        • Sharon Regional Cancer Care Center- Hermitage
      • Monroeville, Pennsylvania, 미국, 15146
        • Intercommunity Cancer Center
      • Natrona Heights, Pennsylvania, 미국, 15065
        • Alle-Kiski Medical Center
      • Pittsburgh, Pennsylvania, 미국, 15212
        • Allegheny Cancer Center at Allegheny General Hospital
      • Somerset, Pennsylvania, 미국, 15501
        • Somerset Oncology Center
      • State College, Pennsylvania, 미국, 16803
        • Mount Nittany Medical Center
    • Tennessee
      • Johnson City, Tennessee, 미국, 37604
        • Johnson City Medical Center Hospital
    • Texas
      • Houston, Texas, 미국, 77030-4009
        • M. D. Anderson Cancer Center at University of Texas
    • West Virginia
      • Wheeling, West Virginia, 미국, 26003
        • Schiffler Cancer Center at Wheeling Hospital
    • Wisconsin
      • Green Bay, Wisconsin, 미국, 54307-3508
        • St. Vincent Hospital Regional Cancer Center
      • Marinette, Wisconsin, 미국, 54143
        • Bay Area Cancer Care Center at Bay Area Medical Center
  • 캐나다
    • Alberta
      • Edmonton, Alberta, 캐나다, T6G 1Z2
        • Cross Cancer Institute at University of Alberta

참여기준

연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.

자격 기준

공부할 수 있는 나이

18년 이상 (성인, 고령자)

건강한 자원 봉사자를 받아들입니다

아니

연구 대상 성별

모두

설명

Inclusion Criteria:

  1. 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;

  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:

  1. Patients with a history of prior head and neck squamous cancer are ineligible;
  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.

공부 계획

이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.

연구는 어떻게 설계됩니까?

디자인 세부사항

  • 주 목적: 지지 요법
  • 할당: 무작위
  • 중재 모델: 병렬 할당
  • 마스킹: 삼루타

무기와 개입

참가자 그룹 / 팔
개입 / 치료
실험적: Palifermin
Concurrent radiation therapy, cisplatin, and palifermin followed by neck dissection for indicated patients.
생물학적: 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.
의약품: cisplatin
Patients will receive cisplatin (100 mg/m2) administered intravenously on days 1, 22, and 43 of the treatment course.
절차: 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.
방사능: 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.
위약 비교기: Placebo
Concurrent radiation therapy, cisplatin, and placebo followed by neck dissection for indicated patients.
의약품: cisplatin
Patients will receive cisplatin (100 mg/m2) administered intravenously on days 1, 22, and 43 of the treatment course.
절차: 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.
방사능: 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.
다른: 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.

연구는 무엇을 측정합니까?

주요 결과 측정

결과 측정
측정값 설명
기간
Duration of Oral Mucositis as Measured in Terms of Days
기간: Twice-weekly from start of treatment up to 15 weeks after the start of treatment.

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.

2차 결과 측정

결과 측정
측정값 설명
기간
Number of Patients With Grade 3 or 4 Mucositis as Measured by the World Heath Organization (WHO) Scale
기간: 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.
Twice-weekly from start of treatment up to 15 weeks after the start of treatment.
Time to Onset of Grade 3 or 4 Oral Mucositis as Measured by the World Heath Organization (WHO) Scale
기간: 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.
Twice-weekly from start of treatment up to 15 weeks after the start of treatment.
Overall Survival
기간: From randomization to maximum follow-up at time of analysis of 21 months
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.
From randomization to maximum follow-up at time of analysis of 21 months
Progression-free Survival
기간: From randomization to maximum follow-up at time of analysis of 21 months
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.
From randomization to maximum follow-up at time of analysis of 21 months
Time to Second Primary Tumor
기간: From randomization to maximum follow-up at time of analysis of 21 months
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

공동 작업자 및 조사자

여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.

스폰서

Radiation Therapy Oncology Group

협력자

National Cancer Institute (NCI)

수사관

  • 연구 의자: David I. Rosenthal, MD, M.D. Anderson Cancer Center

연구 기록 날짜

이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.

연구 주요 날짜

연구 시작

2006년 7월 1일

기본 완료 (실제)

2008년 5월 1일

연구 완료 (실제)

2009년 2월 1일

연구 등록 날짜

최초 제출

2006년 8월 3일

QC 기준을 충족하는 최초 제출

2006년 8월 3일

처음 게시됨 (추정)

2006년 8월 7일

연구 기록 업데이트

마지막 업데이트 게시됨 (실제)

2017년 12월 26일

QC 기준을 충족하는 마지막 업데이트 제출

2017년 11월 28일

마지막으로 확인됨

2017년 11월 1일

추가 정보

이 연구와 관련된 용어

키워드

추가 관련 MeSH 약관

기타 연구 ID 번호

  • RTOG-0435
  • CDR0000491088

약물 및 장치 정보, 연구 문서

미국 FDA 규제 의약품 연구

아니

미국 FDA 규제 기기 제품 연구

아니

미국에서 제조되어 미국에서 수출되는 제품

아니

이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .

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