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

NCT00360971 | Terminated Phase 3 Results DMC

• 2 other identifiers: RTOG-0435CDR0000491088
• Study Type: interventional
• Target: 21
• Locations: 2 countries
• Sites: 48

Brief 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. 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.

Conditions

Head and Neck Cancer; Mucositis; Pain; Radiation Toxicity

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

Outcome Measures

Primary Outcomes (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.

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

Secondary Outcomes (5)

• Number of Patients With Grade 3 or 4 Mucositis as Measured by the World Heath Organization (WHO) Scale

  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

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

• Overall Survival

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

• Progression-free Survival

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

• Time to Second Primary Tumor

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

Study Arms (2)

Palifermin

EXPERIMENTAL

Concurrent radiation therapy, cisplatin, and palifermin followed by neck dissection for indicated patients.

Biological: palifermin; Drug: cisplatin; Procedure: neck dissection; Radiation: radiation therapy

Placebo

PLACEBO COMPARATOR

Concurrent radiation therapy, cisplatin, and placebo followed by neck dissection for indicated patients.

Drug: cisplatin; Other: placebo; Procedure: neck dissection; Radiation: radiation therapy

Interventions

palifermin BIOLOGICAL

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.

Palifermin

cisplatin DRUG

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

Palifermin; Placebo

placebo OTHER

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.

Placebo

neck dissection PROCEDURE

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.

Palifermin; Placebo

radiation therapy RADIATION

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.

Palifermin; Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• 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:
• History/physical examination, including documentation of tobacco/alcohol use and current medications (including opioids/dosing), within 8 weeks prior to registration;
• Chest x-ray (or Chest CT scan) within 6 weeks prior to registration;
• MRI or CT scan with contrast of tumor site within 6 weeks prior to registration;
• 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:
• Absolute neutrophil count (ANC) \> 1,800 cells/mm3 based upon CBC/differential obtained within 2 weeks prior to registration on study
• Platelets \> 100,000 cells/mm3 based upon CBC/differential obtained within 2 weeks prior to registration on study
• 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.)

You may not qualify if:

• 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:
• Symptomatic and/or uncontrolled cardiac disease, New York Heart Association Classification III or IV (see Appendix II);
• Transmural myocardial infarction within the last 6 months;
• Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration;
• Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration.
• Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects;
• Patients known to be sero-positive for hepatitis B virus (HBV) or hepatitis C virus (HCV);
• 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.
• A history of pancreatitis.

Sponsors & Collaborators

• Radiation Therapy Oncology Group: lead
• National Cancer Institute (NCI): collaborator

Study Sites (48)

Mayo Clinic Scottsdale

Scottsdale, Arizona, 85259-5499, United States

Location

Auburn Radiation Oncology

Auburn, California, 95603, United States

Location

Providence Saint Joseph Medical Center - Burbank

Burbank, California, 91505, United States

Location

Radiation Oncology Centers - Cameron Park

Cameron Park, California, 95682, United States

Location

Mercy Cancer Center at Mercy San Juan Medical Center

Carmichael, California, 95608, United States

Location

Enloe Cancer Center at Enloe Medical Center

Chico, California, 95926, United States

Location

City of Hope Comprehensive Cancer Center

Duarte, California, 91010-3000, United States

Location

USC/Norris Comprehensive Cancer Center and Hospital

Los Angeles, California, 90089-9181, United States

Location

Radiation Oncology Center - Roseville

Roseville, California, 95661, United States

Location

Radiological Associates of Sacramento Medical Group, Incorporated

Sacramento, California, 95815, United States

Location

Mercy General Hospital

Sacramento, California, 95819, United States

Location

Torrance Memorial Medical Center

Torrance, California, 90509, United States

Location

Solano Radiation Oncology Center

Vacaville, California, 95687, United States

Location

CCOP - Christiana Care Health Services

Newark, Delaware, 19713, United States

Location

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

Anderson, Indiana, 46016, United States

Location

St. Agnes Hospital Cancer Center

Baltimore, Maryland, 21229, United States

Location

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201-1379, United States

Location

Dickinson County Healthcare System

Iron Mountain, Michigan, 49801, United States

Location

Borgess Medical Center

Kalamazoo, Michigan, 49001, United States

Location

West Michigan Cancer Center

Kalamazoo, Michigan, 49007-3731, United States

Location

Bronson Methodist Hospital

Kalamazoo, Michigan, 49007, United States

Location

William Beaumont Hospital - Royal Oak Campus

Royal Oak, Michigan, 48073, United States

Location

Mayo Clinic Cancer Center

Rochester, Minnesota, 55905, United States

Location

CentraCare Clinic - River Campus

Saint Cloud, Minnesota, 56303, United States

Location

Regional Cancer Center at Singing River Hospital

Pascagoula, Mississippi, 39581, United States

Location

Great Falls Clinic - Main Facility

Great Falls, Montana, 59405, United States

Location

Cancer Institute of New Jersey at Cooper University Hospital - Camden

Camden, New Jersey, 08103, United States

Location

Franklin & Edith Scarpa Regional Cancer Center at South Jersey Healthcare

Vineland, New Jersey, 08360, United States

Location

Cancer Institute of New Jersey at Cooper - Voorhees

Voorhees Township, New Jersey, 08043, United States

Location

Duke Comprehensive Cancer Center

Durham, North Carolina, 27710, United States

Location

Leo W. Jenkins Cancer Center at ECU Medical School

Greenville, North Carolina, 27835-6028, United States

Location

McDowell Cancer Center at Akron General Medical Center

Akron, Ohio, 44307, United States

Location

Summa Center for Cancer Care at Akron City Hospital

Akron, Ohio, 44309-2090, United States

Location

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

Salem, Ohio, 44460, United States

Location

Cancer Treatment Center

Wooster, Ohio, 44691, United States

Location

Oklahoma University Cancer Institute

Oklahoma City, Oklahoma, 73104, United States

Location

Sharon Regional Cancer Care Center- Hermitage

Hermitage, Pennsylvania, 16148, United States

Location

Intercommunity Cancer Center

Monroeville, Pennsylvania, 15146, United States

Location

Alle-Kiski Medical Center

Natrona Heights, Pennsylvania, 15065, United States

Location

Allegheny Cancer Center at Allegheny General Hospital

Pittsburgh, Pennsylvania, 15212, United States

Location

Somerset Oncology Center

Somerset, Pennsylvania, 15501, United States

Location

Mount Nittany Medical Center

State College, Pennsylvania, 16803, United States

Location

Johnson City Medical Center Hospital

Johnson City, Tennessee, 37604, United States

Location

M. D. Anderson Cancer Center at University of Texas

Houston, Texas, 77030-4009, United States

Location

Schiffler Cancer Center at Wheeling Hospital

Wheeling, West Virginia, 26003, United States

Location

St. Vincent Hospital Regional Cancer Center

Green Bay, Wisconsin, 54307-3508, United States

Location

Bay Area Cancer Care Center at Bay Area Medical Center

Marinette, Wisconsin, 54143, United States

Location

Cross Cancer Institute at University of Alberta

Edmonton, Alberta, T6G 1Z2, Canada

Location

MeSH Terms

Conditions

Head and Neck Neoplasms; Mucositis; Pain; Radiation Injuries; Squamous Cell Carcinoma of Head and Neck

Interventions

Fibroblast Growth Factor 7; Cisplatin; Neck Dissection; Radiotherapy

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Mouth Diseases; Stomatognathic Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Wounds and Injuries; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Fibroblast Growth Factors; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Lymph Node Excision; Surgical Procedures, Operative; Otorhinolaryngologic Surgical Procedures; Therapeutics

Limitations and Caveats

This study terminated early with 21 subjects accrued out of 298 planned, therefore no statistical testing was performed. The termination was decided due to positive preliminary results from other palifermin studies.

Results Point of Contact

• Title: Wendy Seiferheld
• Organization: NRG Oncology

seiferheldw@nrgoncology.org

Study Officials

• David I. Rosenthal, MD

  M.D. Anderson Cancer Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 3, 2006
• First Posted: August 7, 2006
• Study Start: July 1, 2006
• Primary Completion: May 1, 2008
• Study Completion: February 1, 2009
• Last Updated: December 26, 2017
• Results First Posted: May 15, 2014

Record last verified: 2017-11

Locations

CA (1); US (47)