A Study of Palifermin for the Reduction of Oral Mucositis in Patients With Locally Advanced Head and Neck Cancer Receiving Postoperative Radiotherapy and Concurrent Chemotherapy

NCT00626639 | Completed Phase 1 Results DMC

• 1 other identifier: 20040124
• Study Type: interventional
• Target: 5
• Locations: 0 countries
• Sites: N/A

Brief Summary

Oral Mucositis associated with adjuvant radiation and concurrent chemotherapy in postoperative Head and Neck setting

Conditions

Mucositis; Head and Neck Cancer

Keywords

palifermin; Clinical Trial; Oncology; Head & Neck

Outcome Measures

Primary Outcomes (3)

• Number of Participants With Adverse Events (AEs)

  An adverse event is an undesirable medical occurrence (sign, symptom, or diagnosis) or worsening of a pre-existing medical condition occurring after start of study drug up to the end of acute oral mucositis (OM) evaluation phase, whether or not considered to be study drug related. If severe OM was not resolved by Week 12, AEs were documented until resolution of severe OM or Week 15, whichever occurred first. A serious AE is any event that is fatal, life threatening, requires or prolongs hospitalization, is a persistent or significant disability/incapacity or is a congenital anomaly/birth defect. The intensity of AEs was graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v3 based on the following: 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. A Protocol-specific Limiting Toxicity (PSLT) is any non-hematologic Grade 3 or 4 AE considered related to study drug.

  Up to Week 12 (or Week 15 for participants with severe OM was not resolved by Week 12)

• Ratio of Ki67-positive Cells Before and After Palifermin Treatment

  The effect of palifermin on cell proliferation was to be assayed by staining for the cell cycle proliferation marker Ki67 in buccal mucosal biopsy samples taken prior to the first dose and either 24 or 48 hours after the first dose. Due to the small sample size, this analysis was not performed.

  Day -3 predose and 24 or 48 hours post-dose

• Pharmacokinetics of Palifermin

  Due to the small sample size this analysis was not performed.

  Day -3, predose and at 2, 5, 15, 30, 60, and 90 minutes and 2, 4, 6, 8, 10, 12, 24 and 48 hours after the first dose

Secondary Outcomes (4)

• Number of Participants With Severe Oral Mucositis (OM) (Adapted RTOG/EORTC Grade ≥3)

  Assessed daily up to Week 12 (or Week 15 if severe oral mucositis not resolved ≤ adapted RTOG/EORTC Grade 2 by Week 12).

• Patient-Reported Mouth and Throat Soreness Score

  Assessed daily up to Week 12 (or Week 15 if severe oral mucositis not resolved ≤ adapted RTOG/EORTC Grade 2 by Week 12).

• Number of Participants With Disease Progression by Week 12

  Up to Week 12

• Overall Survival

  During long-term follow-up phase, until December 2015

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Three days before the start of radiotherapy (Day -3), participants received a single intravenous (IV) bolus injection of matching placebo. During radiotherapy (beginning on Day 1), participants received a weekly single IV bolus injection of matching placebo after the last radiation fraction of that week (usually on Fridays) until grade ≥3 oral mucositis occurred, or for a maximum 8 doses (completion of radiotherapy). Participants also received cisplatin 100 mg/m\^2 on days 1, 22 and 43.

Drug: Placebo; Radiation: Radiotherapy; Drug: Cisplatin

Palifermin

EXPERIMENTAL

Three days before the start of radiotherapy (Day -3), participants received a single intravenous (IV) bolus injection of palifermin at 120 μg/kg. During radiotherapy (beginning on Day 1), participants received a weekly single IV bolus injection of palifermin at 120 μg/kg after the last radiation fraction of that week (usually on Fridays) until grade ≥3 oral mucositis occurred, or for a maximum 8 doses (completion of radiotherapy). Participants also received cisplatin 100 mg/m\^2 on days 1, 22 and 43.

Drug: palifermin; Radiation: Radiotherapy; Drug: Cisplatin

Interventions

Placebo DRUG

Administered by intravenous (IV) bolus injection

Placebo

palifermin DRUG

Administered by intravenous (IV) bolus injection

Palifermin

Radiotherapy RADIATION

Once daily irradiation of 20 centigray (cGy)/day x 33 fractions for a total target dose of 6600 cGy (conventional radiation therapy using standard fractionation \[one fraction per day\])

Palifermin; Placebo

Cisplatin DRUG

100 mg/m\^2 intravenously (IV) on days 1, 22 and 43.

Palifermin; Placebo

Eligibility Criteria

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

You may qualify if:

• History of newly diagnosed histologically confirmed squamous cell carcinoma (American Joint Committee on Cancer \[AJCC\] Stage II, III, IVA, or IVB) involving either the oral cavity, oropharynx, nasopharynx, hypopharynx, or larynx, post surgical resection (R0, R1)
• Scheduled to receive adjuvant concurrent chemoradiation treatment within 12 weeks of surgery
• High-risk subject defined by presence of at least one of the following: R1 resection margins; T3 or T4 tumor stage; 3 or more positive lymph node metastases; \<3 lymph node metastases with extracapsular extension of the disease
• Radiation treatment field to receive planned dose of at least 50Gy to areas of the oral cavity/oropharynx mucosa that can be visualized

You may not qualify if:

• Tumors of the lips, paranasal sinuses, salivary glands, or of unknown primary tumors
• Metastatic disease (M1) / Stage IV C
• Presence or history of any other primary malignancy
• History of pancreatitis
• Prior radiotherapy to the site of disease
• Prior chemotherapy
• Other investigational procedures
• Thirty days or less since receiving an investigational product or device in another clinical trial. Current enrollment in another clinical trial is not permitted unless the sole purpose of the trial is for long-term follow-up/survival data

Sponsors & Collaborators

• Swedish Orphan Biovitrum: lead
• Amgen: collaborator

MeSH Terms

Conditions

Mucositis; Head and Neck Neoplasms; Neoplasms

Interventions

Fibroblast Growth Factor 7; Radiotherapy; Cisplatin

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Mouth Diseases; Stomatognathic Diseases; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Fibroblast Growth Factors; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Therapeutics; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Limitations and Caveats

Pharmacokinetic, pharmacodynamic, safety and efficacy endpoints were not evaluable due to the limited number of subjects enrolled.

Results Point of Contact

• Title: Hans Olivecrona, MD PhD
• Organization: Biovitrum

hans.olivecrona@sobi.com

+46 8 697 20 00

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 21, 2008
• First Posted: February 29, 2008
• Study Start: July 1, 2005
• Primary Completion: May 1, 2007
• Study Completion: July 1, 2015
• Last Updated: June 21, 2017
• Results First Posted: March 6, 2014

Record last verified: 2017-05