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

2017年11月28日 更新者：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.

調査の概要

状態

終了しました

条件

介入・治療

詳細な説明

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.

研究の種類

介入

入学 (実際)

21

段階

  • フェーズ 3

連絡先と場所

このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。

研究場所

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

参加基準

研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。

適格基準

就学可能な年齢

18年歳以上 (大人、高齢者)

健康ボランティアの受け入れ

いいえ

受講資格のある性別

全て

説明

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.

研究計画

このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。

研究はどのように設計されていますか？

デザインの詳細

  • 主な目的：支持療法
  • 割り当て：ランダム化
  • 介入モデル：並列代入
  • マスキング：トリプル

武器と介入

参加者グループ / アーム
介入・治療
実験的：Palifermin
Concurrent radiation therapy, cisplatin, and palifermin followed by neck dissection for indicated patients.
生物学的：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.
薬：cisplatin
Patients will receive cisplatin (100 mg/m2) administered intravenously on days 1, 22, and 43 of the treatment course.
手順：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.
放射線：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.
プラセボコンパレーター：Placebo
Concurrent radiation therapy, cisplatin, and placebo followed by neck dissection for indicated patients.
薬：cisplatin
Patients will receive cisplatin (100 mg/m2) administered intravenously on days 1, 22, and 43 of the treatment course.
手順：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.
放射線：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.
他の：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.

この研究は何を測定していますか？

主要な結果の測定

結果測定
メジャーの説明
時間枠
Duration of Oral Mucositis as Measured in Terms of Days
時間枠：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.

二次結果の測定

結果測定
メジャーの説明
時間枠
Number of Patients With Grade 3 or 4 Mucositis as Measured by the World Heath Organization (WHO) Scale
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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

協力者と研究者

ここでは、この調査に関係する人々や組織を見つけることができます。

スポンサー

Radiation Therapy Oncology Group

協力者

National Cancer Institute (NCI)

捜査官

  • スタディチェア：David I. Rosenthal, MD、M.D. Anderson Cancer Center

研究記録日

これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。

主要日程の研究

研究開始

2006年7月1日

一次修了 (実際)

2008年5月1日

研究の完了 (実際)

2009年2月1日

試験登録日

最初に提出

2006年8月3日

QC基準を満たした最初の提出物

2006年8月3日

最初の投稿 (見積もり)

2006年8月7日

学習記録の更新

投稿された最後の更新 (実際)

2017年12月26日

QC基準を満たした最後の更新が送信されました

2017年11月28日

最終確認日

2017年11月1日

詳しくは

本研究に関する用語

キーワード

追加の関連 MeSH 用語

その他の研究ID番号

  • RTOG-0435
  • CDR0000491088

医薬品およびデバイス情報、研究文書

米国FDA規制医薬品の研究

いいえ

米国FDA規制機器製品の研究

いいえ

米国で製造され、米国から輸出された製品。

いいえ

この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。

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