Study in Head and Neck Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Eli Lilly and Company
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01099358
First received: March 30, 2010
Last updated: September 19, 2014
Last verified: September 2014
  Purpose

The primary purpose of this study is to help answer the following research question(s):

  • To see how the body absorbs, processes, and gets rid of cetuximab when the drug is taken in combination with cisplatin [pharmacokinetic (PK) analysis]
  • To see if any drug interactions occur between cetuximab and cisplatin.

Condition Intervention Phase
Head and Neck Neoplasms
Drug: Cetuximab
Drug: Cisplatin
Drug: 5 - Fluorouracil
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: Phase 2 Study to Evaluate the Pharmacokinetics and Drug-Drug Interaction of Cetuximab and Cisplatin in Patients With Recurrent or Metastatic Carcinoma of the Head and Neck

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Cisplatin pharmacokinetics: Area under the curve (AUC) [ Time Frame: Baseline (prior to Cisplatin infusion); 1, 1:30, 2, 3, 5, 8, 24, 72 hours (after the start of Cisplatin infusion) on Day 1 of weeks 1 and 5 ] [ Designated as safety issue: No ]
  • Cetuximab pharmacokinetics: Area under the curve (AUC) [ Time Frame: Baseline (prior to Cetuximab infusion); 1, 2, 4, 8, 24, 72, 120, and 168 hours (after the start of Cetuximab infusion) on Day 1 of weeks 4 and 5 ] [ Designated as safety issue: No ]
  • Cisplatin pharmacokinetics: Maximum plasma concentration (Cmax) [ Time Frame: Baseline (prior to Cisplatin infusion); 1, 1:30, 2, 3, 5, 8, 24, 72 hours (after the start of Cisplatin infusion) on Day 1 of weeks 1 and 5 ] [ Designated as safety issue: No ]
  • Cetuximab pharmacokinetics: Maximum plasma concentration (Cmax) [ Time Frame: Baseline (prior to Cetuximab infusion); 1, 2, 4, 8, 24, 72, 120, and 160 hours (after the start of Cetuximab infusion) on Day 1 of weeks 4 and 5 ] [ Designated as safety issue: No ]
  • Cisplatin pharmacokinetics: Measurement of the time after administration when the maximum plasma concentration is reached (Tmax) [ Time Frame: Baseline (prior to Cisplatin infusion); 1, 1:30, 2, 3, 5, 8, 24, 72 hours (after the start of Cisplatin infusion) on Day 1 of weeks 1 and 5 ] [ Designated as safety issue: No ]
  • Cetuximab pharmacokinetics: Measurement of the time after administration when the maximum plasma concentration is reached (Tmax) [ Time Frame: Baseline (prior to Cetuximab infusion); 1, 2, 4, 8, 24, 72, 120, and 160 hours (after the start of Cetuximab infusion) on Day 1 of weeks 4 and 5 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Anti-Cetuximab antibodies [ Time Frame: Day 1 of week 1 in Cycles 1, 3, 5, and 30 days after last dose (estimated at up to 6 months) ] [ Designated as safety issue: No ]
  • Objective response rate (ORR) The proportion of participants achieving a best overall response of confirmed partial or complete response (CR + PR), according to RECIST [ Time Frame: From randomization until the date of disease progression/recurrence (estimated at up to 12 months) ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Baseline to date of death from any cause (estimated at up to 36 months) ] [ Designated as safety issue: No ]

Estimated Enrollment: 15
Study Start Date: April 2010
Estimated Study Completion Date: August 2016
Estimated Primary Completion Date: August 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cetuximab and Cisplatin

Cycle 1 (4 weeks, combination therapy): Week 1 - Cisplatin 100 milligrams per square meter (mg/m^2); 5-FU 1000 mg/m^2 on days 1-4. Week 2 - Cetuximab 400 mg/m^2 on day 1. Week 3 - Cetuximab 250 mg/m^2 on day 1. Week 4 - Cetuximab 250 mg/m^2 on day 1.

Cycle 2-6 (3 weeks combination therapy): Week 1 - Cisplatin 100 mg/m^2; 5-FU 1000 mg/m^2 on days 1-4; Cetuximab 250 mg/m^2 on day 1. Week 2 - Cetuximab 250 mg/m^2 on day 1. Week 3 - Cetuximab 250 mg/m^2 on day 1.

After 6 cycles, participants may then receive weekly Cetuximab monotherapy until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.

Drug: Cetuximab
Administered Intravenously
Drug: Cisplatin
Administered Intravenously
Drug: 5 - Fluorouracil
Administered Intravenously
Experimental: Cetuximab on Cisplatin

Cycle 1:

Week 1 - Cisplatin 100 mg/m^2; 5-FU 1000 mg/m^2 on days 1-4 Week 2 - Cetuximab 400 mg/m^2 on day 1 Week 3 - Cetuximab 250 mg/m^2 on day 1

Cycle 2-6:

Week 1 - Cisplatin 100 mg/m^2; 5-FU 1000 mg/m^2 on days 1-4; Cetuximab 250 mg/m^2 on day 1 Week 2 - Cetuximab 250 mg/m^2 on day 1 Week 3 - Cetuximab 250 mg/m^2 on day 1 After 6 cycles, participants may then receive weekly Cetuximab monotherapy until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.

Due to protocol amendment in September 2011, any newly enrolled participants will be placed into Cetuximab and Cisplatin arm only.

Drug: Cetuximab
Administered Intravenously
Drug: Cisplatin
Administered Intravenously
Drug: 5 - Fluorouracil
Administered Intravenously
Experimental: Cisplatin on Cetuximab

Cycle 1:

Week 1 - Cetuximab 400 mg/m^2 on day 1 Week 2 - Cetuximab 250 mg/m^2 on day 1 Week 3 - Cetuximab 250 mg/m^2 on day 1

Cycle 2-7:

Week 1 - Cisplatin 100 mg/m^2; 5-FU 1000 mg/m^2 on days 1-4; Cetuximab 250 mg/m^2 on day 1 Week 2 - Cetuximab 250 mg/m^2 on day 1 Week 3 - Cetuximab 250 mg/m^2 on day 1 After 7 cycles, participants may then receive weekly Cetuximab monotherapy until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.

Due to protocol amendment in September 2011, any newly enrolled participants will be placed into Cetuximab and Cisplatin arm only.

Drug: Cetuximab
Administered Intravenously
Drug: Cisplatin
Administered Intravenously
Drug: 5 - Fluorouracil
Administered Intravenously

  Eligibility

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

Inclusion Criteria:

  • The participant has histologically or cytologically confirmed head and neck cancer, with the exception of lymphomas involving the head and neck region. Tumors of unknown origin presenting in the head and neck region or local or recurrent skin cancers in the head and neck region are also acceptable.
  • The participant has measurable or non-measurable disease.
  • If the patient has received prior treatment with anti-EGFR therapy, the time to recurrence from the last cetuximab or other anti-EGFR agent exposure is > 90 days. If the patient has received therapy with an anti-EGFR tyrosine kinase inhibitor, the time to recurrence from the last exposure is > 30 days.
  • The participant has a life expectancy of greater than 3 months.
  • The participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
  • The participant has adequate hematologic function as defined by absolute neutrophil count greater than or equal to 1500/microliter (μL), hemoglobin greater than or equal to 9 grams/deciliter (g/dL), and platelet count greater than or equal to 100,000/microliter (μL).
  • The participant has adequate hepatic function as defined by a total bilirubin less than or equal to 2 x the upper limit of normal (ULN), aspartate transaminase (AST, SGOT) and alanine transaminase (ALT, SGPT) less than or equal to 3 x the ULN (or less than or equal to 5 x the ULN in the presence of known liver metastases).
  • The participant has adequate renal function as defined by serum creatinine less than or equal to 1.5 x the institutional ULN or creatinine clearance greater than or equal to 60 mL/min for participants with creatinine levels above the ULN.
  • The participant has the ability to understand, and the willingness to sign, a written informed consent document.
  • Prior systemic chemotherapy for head and neck cancer is allowed only if performed as part of a multimodal treatment for locally advanced disease and/or as first-line treatment for recurrent/metastatic disease. The time to recurrence from the last exposure of systemic chemotherapy must be more than 6 weeks. The first-line treatment for recurrent/metastatic disease must not have contained a platinum agent.

Exclusion Criteria:

  • The participant has lymphoma involving the head or neck region.
  • The participant has symptomatic brain or leptomeningeal metastasis.
  • The participant has not recovered from Adverse Events due to agents administered more than 4 weeks earlier. Neurotoxicity, if present, must have improved to Grade less than 2 per the National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) v 3.0.
  • The participant is receiving any other investigational agent(s).
  • The participant is receiving concurrent treatment with other anticancer therapy, including chemotherapy, immunotherapy, hormonal therapy, RT, chemoembolization, or targeted therapy. Participants receiving palliative radiation therapy to bony metastases prior to the first dose of study medication are eligible.
  • The participant is receiving therapy with immunosuppressive agents.
  • The participant has known drug or alcohol abuse.
  • The participant has uncontrolled hypertension defined as systolic blood pressure greater than or equal to 180 millimeters of mercury (mm Hg) or diastolic blood pressure greater than or equal to 130 mm Hg.
  • The participant has a history of allergic reactions attributed to compounds of chemical or biologic composition similar to those of cetuximab or cisplatin.
  • The participant has a medical or psychological condition that would not permit the participant to complete the study or sign informed consent.
  • The participant has clinically relevant coronary artery disease or history of myocardial infarction in the last 12 months or high risk of uncontrolled arrhythmia or uncontrolled cardiac insufficiency.
  • The participant, if female, is pregnant (confirmed by serum or urine beta-human chorionic gonadotropin [β-HCG] pregnancy test) or breastfeeding
  • The participant has had a known positive test result for the human immunodeficiency virus.
  • The participant has an active infection (requiring intravenous [IV] antibiotics), including tuberculosis.
  • The participant has a history of another active primary invasive cancer within the previous 2 years, excluding non-melanoma skin cancer.
  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: NCT01099358

Contacts
Contact: There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559

Locations
United States, Kansas
University of Kansas Medical Center Recruiting
Fairway, Kansas, United States, 66205
Contact    913-945-5059      
Principal Investigator: Raymond Perez         
United States, Nevada
VA Sierra Nevada Health Care System Recruiting
Reno, Nevada, United States, 89502
Contact    775-328-1828      
Principal Investigator: Frederick MacKintosh         
United States, North Carolina
University of North Carolina Recruiting
Chapel Hill, North Carolina, United States, 27599
Contact    919-966-3786      
Principal Investigator: Neil Hayes         
United States, Texas
University of Texas Health Science Center - San Antonio Active, not recruiting
San Antonio, Texas, United States, 78229
Canada, Ontario
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Recruiting
London, Ontario, Canada, N6A 4L6
Contact: Eli Lilly and Company         
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Recruiting
Toronto, Ontario, Canada, M5G 2M9
Contact: Eli Lilly and Company         
Canada, Quebec
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Recruiting
Montreal, Quebec, Canada, H3G 1A4
Contact: Eli Lilly and Company         
Sponsors and Collaborators
Eli Lilly and Company
Investigators
Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) Eli Lilly and Company
  More Information

No publications provided

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01099358     History of Changes
Other Study ID Numbers: 13418, I4E-MC-JXBA
Study First Received: March 30, 2010
Last Updated: September 19, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Eli Lilly and Company:
Cancer of Head and Neck
Cancer of the Head and Neck
Head and Neck Cancer
Cancer of Head
Cancer of Neck
Cancer of the Head
Cancer of the Neck
Head Cancer
Head Neoplasms
Head, Neck Neoplasms
Neck Cancer
Neck Neoplasms

Additional relevant MeSH terms:
Head and Neck Neoplasms
Neoplasms
Neoplasms by Site
Cetuximab
Cisplatin
Fluorouracil
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 01, 2014