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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Amgen
Information provided by (Responsible Party):
Swedish Orphan Biovitrum
ClinicalTrials.gov Identifier:
NCT00094861
First received: October 27, 2004
Last updated: January 24, 2014
Last verified: January 2014
  Purpose

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).


Condition Intervention Phase
Dysphagia
Non-Small Cell Lung Cancer
Lung Cancer
Drug: Palifermin
Drug: Placebo
Radiation: Radiotherapy
Drug: Paclitaxel
Drug: Carboplatin
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Swedish Orphan Biovitrum:

Primary Outcome Measures:
  • Number of Participants With Grade 2 or Higher Dysphagia [ Time Frame: Start of treatment through Week 16 ] [ Designated as safety issue: Yes ]

    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).



Secondary Outcome Measures:
  • Duration of Grade 2 or Higher Dysphagia [ Time Frame: Start of treatment through Week 16 ] [ Designated as safety issue: No ]

    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.


  • Maximal Dysphagia Grade [ Time Frame: Start of treatment through Week 16 ] [ Designated as safety issue: No ]

    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).


  • Number of Participants With Severe (Grade 3 or Higher) Dysphagia [ Time Frame: Start of treatment through Week 16 ] [ Designated as safety issue: No ]

    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).


  • Number of Participants With Unplanned Breaks in Radiotherapy [ Time Frame: Week 1 to Week 6 ] [ Designated as safety issue: No ]
    The number of participants with unplanned breaks in radiotherapy of ≥ 5 days or who discontinued radiotherapy during Week 1 to Week 6.

  • Maximal Eastern Cooperative Oncology Group (ECOG) Performance Status Increase [ Time Frame: Baseline through Week 12 ] [ Designated as safety issue: No ]

    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.


  • Number of Participants Hospitalized [ Time Frame: Baseline to Week 16 ] [ Designated as safety issue: No ]
  • Maximal Body Weight Loss [ Time Frame: Baseline through Week 12 ] [ Designated as safety issue: No ]
    Maximal weight loss observed from Baseline through to Week 12.


Enrollment: 100
Study Start Date: January 2005
Estimated Study Completion Date: February 2015
Primary Completion Date: December 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo

Participants received a single intravenous (IV) dose of placebo administered 3 days before the initiation of concurrent chemo/radiotherapy, then once weekly during Weeks 1 through 6, typically for a total of 7 doses. Concurrent radio/chemotherapy was given as follows:

  • standard radiotherapy 2 Gy once daily x 30 to 33 fractions (6 to 7 weeks) for a total target dose of 60 to 66 Gy
  • paclitaxel 50 mg/m^2 intravenous (IV) infusion on Days 1, 8, 15, 22, 29, 36 (and day 43 for those receiving 66 Gy)
  • carboplatin dosed at an area under the curve (AUC) 2.0 IV on Days 1, 8, 15, 22, 29, 36 (and day 43 for those receiving 66 Gy).

Participants subsequently received two 21-day cycles of consolidation chemotherapy with paclitaxel 225 mg/m^2 and carboplatin dosed at AUC 6.0.

Drug: Placebo Radiation: Radiotherapy Drug: Paclitaxel Drug: Carboplatin
Experimental: Palifermin

Participants received a single IV dose of palifermin at 180 μg/kg administered 3 days before the initiation of concurrent chemo/radiotherapy, then once weekly during Weeks 1 through 6, typically for a total of 7 doses. Concurrent radio/chemotherapy (administered for 6 to 7 weeks) was given as follows:

  • standard radiotherapy 2 Gy once daily x 30 to 33 fractions (6 to 7 weeks) for a total target dose of 60 to 66 Gy
  • paclitaxel 50 mg/m^2 IV infusion on Days 1, 8, 15, 22, 29, 36 (and day 43 for those receiving 66 Gy)
  • carboplatin dosed at an area under the curve (AUC) 2.0 IV on Days 1, 8, 15, 22, 29, 36 (and day 43 for those receiving 66 Gy).

Participants subsequently received two 21-day cycles of consolidation chemotherapy with paclitaxel 225 mg/m^2 and carboplatin dosed at AUC 6.0.

Drug: Palifermin
Other Names:
  • Recombinant Human Keratinocyte Growth Factor
  • rHuKGF
  • Kepivance
Radiation: Radiotherapy Drug: Paclitaxel Drug: Carboplatin

Detailed 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).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00094861

Sponsors and Collaborators
Swedish Orphan Biovitrum
Amgen
Investigators
Study Director: MD Amgen
  More Information

No publications provided

Responsible Party: Swedish Orphan Biovitrum
ClinicalTrials.gov Identifier: NCT00094861     History of Changes
Other Study ID Numbers: 20030185
Study First Received: October 27, 2004
Results First Received: January 24, 2014
Last Updated: January 24, 2014
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Spain: Agencia Española de Medicamentos y Productos Sanitarios
United States: Food and Drug Administration

Keywords provided by Swedish Orphan Biovitrum:
dysphagia
palifermin, KGF
chemoradiotherapy
NSCLC, non-small cell lung cancer
lung cancer
supportive care
clinical trial
consolidation chemotherapy
radiotherapy

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Deglutition Disorders
Lung Neoplasms
Bronchial Neoplasms
Carcinoma, Bronchogenic
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Lung Diseases
Neoplasms
Neoplasms by Site
Otorhinolaryngologic Diseases
Pharyngeal Diseases
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Carboplatin
Mitogens
Paclitaxel
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on October 21, 2014