Study to Evaluate Palifermin in the Reduction of Dysphagia in Patients With Locally Advanced Non-Small Cell Lung Cancer (NSCLC)

Lung Cancer Clinical Trial

Official title:

A Phase 2 Study to Evaluate the Efficacy and Safety of Palifermin (Recombinant Human Keratinocyte Growth Factor) in the Reduction of Dysphagia in Patients Receiving Concurrent Chemoradiotherapy Followed by Consolidation Chemotherapy for Locally Advanced Non-Small Cell Lung Cancer (NSCLC)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00094861
• Other study ID #: 20030185
• Status: Completed
• Phase: Phase 2
• First received: October 27, 2004
• Last updated: December 11, 2014
• Start date: January 2005
• Est. completion date: January 2014

Study information

• Verified date: December 2014
• Source: Swedish Orphan Biovitrum
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: Federal Institute for Drugs and Medical DevicesPoland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsSpain: Agencia Española de Medicamentos y Productos SanitariosUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine if palifermin will reduce the incidence of dysphagia in patients receiving concurrent chemoradiotherapy followed by consolidation chemotherapy for treatment of unresectable stage III Non-Small Cell Lung Cancer (NSCLC).

Description:

During the acute dysphagia evaluation phase (the period lasting from the administration of the first dose of investigational product through Week 12 (or up to Week 16 if dysphagia is not resolved to CTCAE v3.0 grade ≤ 1 by Week 12) participants underwent acute dysphagia assessments twice weekly. All participants were followed for disease progression, second primary tumors, other malignancies, and overall survival until death or loss to follow-up during the long term follow-up (still ongoing).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: January 2014
• Est. primary completion date: December 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients with a histologically or cytologically proven diagnosis of NSCLC

• Unresectable (locally advanced) stage IIIa or IIIb disease

• Initial radiotherapy field of treatment to encompass greater than or equal to 30% of the esophagus

• Life expectancy greater than or equal to 6 months

• Estimated weight loss less than or equal to 10% in the 3 months before study randomization

• Measurable disease

• 18 years of age or older

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2

• Hemoglobin (hgb) greater than or equal to 10 g/dL without transfusional support or growth factor use in the 4 weeks before study randomization

• Absolute neutrophil count (ANC) greater than or equal to 1.5 x 10^9/L without growth factor use in the 2 weeks before study randomization

• Platelet count greater than or equal to 100 x 10^9/L

• Serum bilirubin less than or equal to 1.5 x institutional upper limit of normal (ULN)

• Serum creatinine less than or equal to 2.0 mg/dL (Note: Patients with a serum creatinine greater than or equal to 1.4 and less than or equal to 2.0 mg/dL must demonstrate a 24-hour urinary creatinine clearance greater than or equal to 50 mL/min)

• Females of childbearing potential: negative serum or urine pregnancy test

• Patient must give written informed consent before participating in any study-specific procedure, randomization, or receiving investigational product.

• Patients with reproductive capability must agree to practice adequate contraception methods.

Exclusion Criteria:

• Metastatic disease (M1)/stage 4 NSCLC

• Pleural or pericardial effusion greater than 100 ml in volume as documented by appropriate imaging (positron emission tomography [PET], computed tomography [CT] scan or ultrasound). If an effusion greater than 100 ml is documented by cytology to be free from malignancy and the investigator feels the patient is capable of receiving chemo/radiotherapy for their primary disease/ NSCLC, the investigator should discuss the patient with the study physician at Amgen. Effusions smaller than 100 ml would be acceptable, unless the investigator suspects that the effusion is malignant, in which case the effusions should be evaluated by cytology. Sponsor approval must be obtained before patient is randomized.

• Plan to remove the tumor surgically before completing the protocol chemo/radiotherapy course

• Shielding of any part of the esophagus during radiotherapy (including posterior spinal cord shielding)

• Prior chemotherapy, radiotherapy, or surgery for NSCLC

• Prior invasive malignancy during the past 3 years other than non-melanomatous skin cancer. Note: Patients with prior surgically-cured malignancies [eg, stage I breast cancer or prostate cancer, in-situ carcinoma of the cervix, etc] are not excluded; however, sponsor approval must be obtained before patient is randomized.

• Presence or history of dysphagia or conditions predisposing to dysphagia (eg, uncontrolled gastroesophageal reflux disease [GERD], dyspepsia, etc)

• History of pancreatitis

• Four weeks or less since completion of treatment using an investigational product/device in another clinical study or presence of any unresolved toxicity from previous treatment

• Previous treatment on this study or with a fibroblast growth factor

• Known to be sero-positive for human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV)

• Pregnant or breastfeeding women

• Known sensitivity to E. coli derived products

• Compromised ability of the patient to give written informed consent and/or to comply with study procedures

• Refusal to sign an informed consent form to participate in this study, and sign the hospital information release form, if applicable

• Unwilling or unable to complete the patient reported outcome (PRO) questionnaires

• Psychological, social, familial, or geographical reasons that would prevent regular follow-up

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Deglutition Disorders
• Dysphagia
• Lung Cancer
• Lung Neoplasms
• Non-Small Cell Lung Cancer

Intervention

Drug:
• Palifermin

• Placebo

Radiation:
• Radiotherapy

Drug:
• Paclitaxel

• Carboplatin

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Swedish Orphan Biovitrum	Amgen

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Grade 2 or Higher Dysphagia	Participants underwent acute dysphagia assessments twice weekly during Weeks 1 through 7, and twice weekly thereafter (Weeks 8 through 12) and once weekly after Week 12 until dysphagia resolved to grade = 1 but not beyond Week 16. Dysphagia (difficulty swallowing) was graded using the Common Terminology Criteria for Adverse Events, Version 3.0 (CTCAE v3.0) dysphagia scale according to the following: Grade 1: Symptomatic, able to eat regular diet; Grade 2: Symptomatic and altered eating/swallowing (e.g., altered dietary habits, oral supplements), IV fluids indicated <24 hours; Grade 3: Symptomatic and severely altered eating/swallowing (e.g., inadequate oral caloric or fluid intake), IV fluids, tube feedings, or total parenteral nutrition (TPN) indicated =24 hours; Grade 4: Life-threatening consequences (e.g., obstruction, perforation).	Start of treatment through Week 16	Yes
Secondary	Duration of Grade 2 or Higher Dysphagia	Duration of grade 2 or higher dysphagia was calculated in days from the onset (first occurrence of grade = 2) to the resolution (grade = 1 after the last grade = 2) of dysphagia.; Participants with no assessments were assumed as having grade = 2 dysphagia and with a duration of the mean duration of all participants.	Start of treatment through Week 16	No
Secondary	Maximal Dysphagia Grade	The mean maximal grade of dysphagia for each participant during the study. Dysphagia (difficulty swallowing) was graded using the Common Terminology Criteria for Adverse Events, Version 3.0 (CTCAE v3.0) dysphagia scale according to the following: Grade 1: Symptomatic, able to eat regular diet; Grade 2: Symptomatic and altered eating/swallowing (e.g., altered dietary habits, oral supplements), IV fluids indicated <24 hours; Grade 3: Symptomatic and severely altered eating/swallowing (e.g., inadequate oral caloric or fluid intake), IV fluids, tube feedings, or total parenteral nutrition (TPN) indicated =24 hours; Grade 4: Life-threatening consequences (e.g., obstruction, perforation).	Start of treatment through Week 16	No
Secondary	Number of Participants With Severe (Grade 3 or Higher) Dysphagia	Participants underwent acute dysphagia assessments twice weekly during Weeks 1 through 7, and twice weekly thereafter (Weeks 8 through 12) and once weekly after Week 12 until dysphagia resolved to grade = 1 but not beyond Week 16. Dysphagia (difficulty swallowing) was graded using the Common Terminology Criteria for Adverse Events, Version 3.0 (CTCAE v3.0) dysphagia scale according to the following: Grade 1: Symptomatic, able to eat regular diet; Grade 2: Symptomatic and altered eating/swallowing (e.g., altered dietary habits, oral supplements), IV fluids indicated <24 hours; Grade 3: Symptomatic and severely altered eating/swallowing (e.g., inadequate oral caloric or fluid intake), IV fluids, tube feedings, or total parenteral nutrition (TPN) indicated =24 hours; Grade 4: Life-threatening consequences (e.g., obstruction, perforation).	Start of treatment through Week 16	No
Secondary	Number of Participants With Unplanned Breaks in Radiotherapy	The number of participants with unplanned breaks in radiotherapy of = 5 days or who discontinued radiotherapy during Week 1 to Week 6.	Week 1 to Week 6	No
Secondary	Maximal Eastern Cooperative Oncology Group (ECOG) Performance Status Increase	Maximal increase from Baseline in Eastern Cooperative Oncology Group (ECOG) performance status. ECOG is a scale to assess how a patient's disease is progressing, how the disease affects the daily living abilities of the patient, and determine appropriate treatment and prognosis.; Grade 0: Fully active, able to carry on all pre-disease performance without restriction; Grade 1: Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature; Grade 2: Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours; Grade 3: Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours; Grade 4: Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair; Grade 5: Dead.	Baseline through Week 12	No
Secondary	Number of Participants Hospitalized		Baseline to Week 16	No
Secondary	Maximal Body Weight Loss	Maximal weight loss observed from Baseline through to Week 12.	Baseline through Week 12	No