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Head and Neck CancerPhase 3NCT00360971

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

A Phase 3 study testing palifermin, cisplatin and neck dissection in people with Head and Neck Cancer and Mucositis, run by Radiation Therapy Oncology Group at 48 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Head and Neck Cancer, Mucositis, Pain
What is being tested?
palifermin, cisplatin and neck dissection
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
21 participants
Where
48 sitesin 2 countries
Study dates
Jul 2006to Feb 2009
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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;
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  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

48 sites in 2 countries.

48 sites in 2 countries

United States47 sites
  • McDowell Cancer Center at Akron General Medical Center

    Akron, Ohio, 44307

  • Summa Center for Cancer Care at Akron City Hospital

    Akron, Ohio, 44309-2090

  • Saint John's Cancer Center at Saint John's Medical Center

    Anderson, Indiana, 46016

  • Auburn Radiation Oncology

    Auburn, California, 95603

  • St. Agnes Hospital Cancer Center

    Baltimore, Maryland, 21229

  • Providence Saint Joseph Medical Center - Burbank

    Burbank, California, 91505

  • Cancer Institute of New Jersey at Cooper University Hospital - Camden

    Camden, New Jersey, 08103

  • Radiation Oncology Centers - Cameron Park

    Cameron Park, California, 95682

  • Mercy Cancer Center at Mercy San Juan Medical Center

    Carmichael, California, 95608

  • Enloe Cancer Center at Enloe Medical Center

    Chico, California, 95926

  • Barbara Ann Karmanos Cancer Institute

    Detroit, Michigan, 48201-1379

  • City of Hope Comprehensive Cancer Center

    Duarte, California, 91010-3000

  • Duke Comprehensive Cancer Center

    Durham, North Carolina, 27710

  • Great Falls Clinic - Main Facility

    Great Falls, Montana, 59405

  • St. Vincent Hospital Regional Cancer Center

    Green Bay, Wisconsin, 54307-3508

  • Leo W. Jenkins Cancer Center at ECU Medical School

    Greenville, North Carolina, 27835-6028

  • Sharon Regional Cancer Care Center- Hermitage

    Hermitage, Pennsylvania, 16148

  • M. D. Anderson Cancer Center at University of Texas

    Houston, Texas, 77030-4009

  • Dickinson County Healthcare System

    Iron Mountain, Michigan, 49801

  • Johnson City Medical Center Hospital

    Johnson City, Tennessee, 37604

  • Borgess Medical Center

    Kalamazoo, Michigan, 49001

  • West Michigan Cancer Center

    Kalamazoo, Michigan, 49007-3731

  • Bronson Methodist Hospital

    Kalamazoo, Michigan, 49007

  • USC/Norris Comprehensive Cancer Center and Hospital

    Los Angeles, California, 90089-9181

  • Bay Area Cancer Care Center at Bay Area Medical Center

    Marinette, Wisconsin, 54143

  • Intercommunity Cancer Center

    Monroeville, Pennsylvania, 15146

  • Alle-Kiski Medical Center

    Natrona Heights, Pennsylvania, 15065

  • CCOP - Christiana Care Health Services

    Newark, Delaware, 19713

  • Oklahoma University Cancer Institute

    Oklahoma City, Oklahoma, 73104

  • Regional Cancer Center at Singing River Hospital

    Pascagoula, Mississippi, 39581

  • Allegheny Cancer Center at Allegheny General Hospital

    Pittsburgh, Pennsylvania, 15212

  • Mayo Clinic Cancer Center

    Rochester, Minnesota, 55905

  • Radiation Oncology Center - Roseville

    Roseville, California, 95661

  • William Beaumont Hospital - Royal Oak Campus

    Royal Oak, Michigan, 48073

  • Radiological Associates of Sacramento Medical Group, Incorporated

    Sacramento, California, 95815

  • Mercy General Hospital

    Sacramento, California, 95819

  • CentraCare Clinic - River Campus

    Saint Cloud, Minnesota, 56303

  • Cancer Research UK Medical Oncology Unit at Churchill Hospital & Weatherall Institute of Molecular Medicine - Oxford

    Salem, Ohio, 44460

  • Mayo Clinic Scottsdale

    Scottsdale, Arizona, 85259-5499

  • Somerset Oncology Center

    Somerset, Pennsylvania, 15501

  • Mount Nittany Medical Center

    State College, Pennsylvania, 16803

  • Torrance Memorial Medical Center

    Torrance, California, 90509

  • Solano Radiation Oncology Center

    Vacaville, California, 95687

  • Franklin & Edith Scarpa Regional Cancer Center at South Jersey Healthcare

    Vineland, New Jersey, 08360

  • Cancer Institute of New Jersey at Cooper - Voorhees

    Voorhees Township, New Jersey, 08043

  • Schiffler Cancer Center at Wheeling Hospital

    Wheeling, West Virginia, 26003

  • Cancer Treatment Center

    Wooster, Ohio, 44691

Other trials in United States

Canada1 site
  • Cross Cancer Institute at University of Alberta

    Edmonton, Alberta, T6G 1Z2

Other trials in Canada

About this study

Official title: 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.

Read the detailed description

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.

Being tested
palifermin, cisplatin, placebo, neck dissection, radiation therapy
Keywords
mucositis, pain, radiation toxicity, stage III squamous cell carcinoma of the hypopharynx, stage IV squamous cell carcinoma of the hypopharynx, stage III squamous cell carcinoma of the larynx, stage IV squamous cell carcinoma of the larynx, stage III squamous cell carcinoma of the lip and oral cavity, stage IV squamous cell carcinoma of the lip and oral cavity, stage III squamous cell carcinoma of the oropharynx, stage IV squamous cell carcinoma of the oropharynx
Medical subject headings
Head and Neck Neoplasms, Mucositis, Pain, Radiation Injuries, Squamous Cell Carcinoma of Head and Neck

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • paliferminBiological

    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.

  • cisplatinDrug

    Patients will receive cisplatin (100 mg/m2) administered intravenously on days 1, 22, and 43 of the treatment course.

  • placeboOther

    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 dissectionProcedure or surgery

    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 therapyRadiation

    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.

Study groups in NCT00360971
Study groupRoleWhat they receive
PaliferminExperimentalConcurrent radiation therapy, cisplatin, and palifermin followed by neck dissection for indicated patients.
Receives: Biological: palifermin; Drug: cisplatin; Procedure: neck dissection; Radiation: radiation therapy
PlaceboPlacebo comparatorConcurrent radiation therapy, cisplatin, and placebo followed by neck dissection for indicated patients.
Receives: Drug: cisplatin; Other: placebo; Procedure: neck dissection; Radiation: radiation therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Duration of Oral Mucositis as Measured in Terms of Days

    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.

    Measured: Twice-weekly from start of treatment up to 15 weeks after the start of treatment.

Secondary outcomes (5)
  1. Number of Patients With Grade 3 or 4 Mucositis as Measured by the World Heath Organization (WHO) Scale

    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.

    Measured: Twice-weekly from start of treatment up to 15 weeks after the start of treatment.

  2. Time to Onset of Grade 3 or 4 Oral Mucositis as Measured by the World Heath Organization (WHO) Scale

    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.

    Measured: Twice-weekly from start of treatment up to 15 weeks after the start of treatment.

  3. Overall Survival

    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.

    Measured: From randomization to maximum follow-up at time of analysis of 21 months

  4. Progression-free Survival

    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.

    Measured: From randomization to maximum follow-up at time of analysis of 21 months

  5. Time to Second Primary Tumor

    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.

    Measured: From randomization to maximum follow-up at time of analysis of 21 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Aug 2006 (estimated)
  2. Study startJul 2006
  3. Primary completionMay 2008
  4. Study completionFeb 2009

Why it stopped: Due to positive preliminary results from other palifermin studies.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Supportive care
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
21 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00360971
Sponsor's protocol ID
RTOG-0435
Other IDs
CDR0000491088
Status last verified
Nov 2017
First submitted
3 Aug 2006
Last updated
26 Dec 2017
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing palifermin, cisplatin and neck dissection in people with Head and Neck Cancer and Mucositis, run by Radiation Therapy Oncology Group at 48 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 26 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 48 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 May 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Duration of Oral Mucositis as Measured in Terms of Days (time frame: Twice-weekly from start of treatment up to 15 weeks after the start of treatment.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Dec 2017.

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