A Study in Advanced Solid Tumors

• ClinicalTrials.gov Identifier: NCT01063075
• Recruitment Status: Completed
• First Posted: February 5, 2010
• Results First Posted: June 15, 2016
• Last Update Posted: September 26, 2019
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Study Description

Brief Summary:

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 carboplatin [pharmacokinetic (PK) analysis]
• To see if any drug interactions occur between cetuximab and carboplatin.

Condition or disease	Intervention/treatment	Phase
Solid Tumor	Drug: Cetuximab; Drug: Carboplatin; Drug: 5 - FU	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 34 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: Phase 2 Study to Evaluate the Pharmacokinetics and Drug-Drug Interaction of Cetuximab and Carboplatin in Patients With Advanced Solid Tumors
• Study Start Date: June 2010
• Actual Primary Completion Date: May 2015
• Actual Study Completion Date: October 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cetuximab and Carboplatin (D); Group D: Cycle 1 (1 week, combination therapy): 400 milligrams per square meter (mg/m ²) cetuximab administered intravenously (I.V) on week 1,day 1. Carboplatin area under the curve (AUC=5) administered I.V on week 1,day 1. Optional 5- fluorouracil (FU) administered as a 96-hour continuous infusion (C.I.) of 1000 mg/ m ²/day administered starting on week 1, day 1. After 1 cycle, participants may then receive cetuximab as determined by clinical exam or radiological imaging studies until progression of disease, unacceptable toxicity, or another withdrawal criterion is met. After protocol amendment February 2014, any newly enrolled participants were placed into Group D only.	Drug: Cetuximab; Administered Intravenously; Drug: Carboplatin; Administered Intravenously; Drug: 5 - FU; Administered Intravenously
Experimental: Cetuximab and Carboplatin (C); Group C: Cycle 1 (4 weeks, combination therapy): Carboplatin (AUC=5) administered I.V on week 1, day 1.1000 mg/m ²/day 5-FU administered as a 96-hour C.I. starting on week 1, day 1. 400 mg/m² cetuximab administered I.V on week 2, day 1. 250 mg/m ² cetuximab administered I.V on week 3 and 4, day 1. Cycle 2-6 (3 weeks, combination therapy): Carboplatin (AUC=5) administered I.V on week1,day1.1000 mg/m ²/d 5-FU as a 96-hour C.I. starting on week1, day1. 250 mg/m ² cetuximab administered I.V on Week 1-3, day 1. After 6 cycles, participants may then receive 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 were placed into cetuximab and carboplatin (C) arm only. After protocol amendment February 2014, any newly enrolled participants will be placed into Group D arm only.	Drug: Cetuximab; Administered Intravenously; Drug: Carboplatin; Administered Intravenously; Drug: 5 - FU; Administered Intravenously
Experimental: Cetuximab and Carboplatin (B); Group B: Cycle 1 (3 weeks, single-agent cetuximab): 400 mg/m² cetuximab administered I.V on week 1, day 1. 250 mg/m ² cetuximab administered I.V on weeks 2 and 3, day 1. Cycle 2 (3 weeks, combination therapy): Carboplatin (AUC=5) administered I.V week 1, day 1. 1000 mg/m ²/d 5-FU administered as a 96-hour C.I. starting on week 1, day 1. 250 mg/m ² cetuximab administered I.V weeks 1- 3,day 1. After 6 cycles, participants may then receive 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 were placed into cetuximab and carboplatin (C) arm only. After protocol amendment February 2014, any newly enrolled participants will be placed into Group D arm only.	Drug: Cetuximab; Administered Intravenously; Drug: Carboplatin; Administered Intravenously; Drug: 5 - FU; Administered Intravenously
Experimental: Carboplatin and Cetuximab (A); Group A: Cycle 1 (3 weeks, combination therapy): Carboplatin (AUC=5) administered I.V on week 1, day 1. 1000 mg/m ²/d 5-FU administered as a 96-hour C.I. starting on week 1, day 1. 400 mg/m ² cetuximab administered I.V on week 2, day 1. 250 mg/m ² cetuximab administered I.V on week 3, day 1. Cycle 2 (3 weeks, combination therapy): Carboplatin (AUC=5) administered I.V on week 1, day 1. 1000 mg/m ²/d 5-FU administered as a 96-hour C.I. starting on week 1, day 1. 250 mg/m ² cetuximab administered I.V on weeks 1- 3, day 1. After 7 cycles, participants may then receive 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 were placed into cetuximab and carboplatin (C) arm only. After protocol amendment February 2014, any newly enrolled participants will be placed into Group D arm only.	Drug: Cetuximab; Administered Intravenously; Drug: Carboplatin; Administered Intravenously; Drug: 5 - FU; Administered Intravenously

Outcome Measures

Primary Outcome Measures :

1. Total Carboplatin Pharmacokinetics (PK): Area Under the Concentration (AUC) Versus Time Curve From Time Zero to Infinity (AUC[0-∞]) [ Time Frame: Group D: Cycle 1, Week 1, Day 1; Prior to Carboplatin Infusion, 1hour (H), 1:30 H, 2 H, 3 H, 5 H, 8 H, 24 H, 72 H (after the Start of Carboplatin Infusion) ]
2. Cetuximab PK: Area Under the Concentration Versus Time Curve During One Dosing Interval at Steady State (AUC τ,ss) [ Time Frame: (Group B: Cycle 1 and Cycle 2+ ; Day 1, 8, 15 and Group C: Cycle 1, Day 8, 15 and 22; Cycle 2+, Day 1,8 and 15): Prior to Cetuximab Infusion, 1 Hour (H), 2 H, 4 H, 8 H, 24 H, 72 H, 120 H, and 168 H (after the start of Cetuximab Infusion) ]
3. Total Carboplatin PK: Maximum Observed Plasma Concentration (Cmax) [ Time Frame: Group D: Cycle 1, Week 1, Day 1; Prior to Carboplatin Infusion, 1hour (H), 1:30 H, 2 H, 3 H, 5 H, 8 H, 24 H, 72 H (after the Start of Carboplatin Infusion) ]
4. Cetuximab PK: Maximum Observed Plasma Concentration at Steady State (Cmax,ss) [ Time Frame: (Group B: Cycle 1 and Cycle 2+ ; Day 1, 8, 15 and Group C: Cycle 1, Day 8, 15 and 22; Cycle 2+, Day 1,8 and 15): Prior to Cetuximab Infusion, 1 Hour (H), 2 H, 4 H, 8 H, 24 H, 72 H, 120 H, and 168 H (after the start of Cetuximab Infusion) ]
5. Total Carboplatin PK: Time of Maximum Observed Plasma Concentration (Tmax) [ Time Frame: Group D: Cycle 1, Week 1, Day 1; Prior to Carboplatin Infusion, 1hour (H), 1:30 H, 2 H, 3 H, 5 H, 8 H, 24 H, 72 H (after the Start of Carboplatin Infusion) ]
6. Cetuximab PK: Time of Maximum Observed Plasma Concentration at Steady State (Tmax,ss) [ Time Frame: (Group B: Cycle 1 and Cycle 2+ ; Day 1, 8, 15 and Group C: Cycle 1, Day 8, 15 and 22; Cycle 2+, Day 1,8 and 15): Prior to Cetuximab Infusion, 1 Hour (H), 2 H, 4 H, 8 H, 24 H, 72 H, 120 H, and 168 H (after the start of Cetuximab Infusion) ]
7. Cetuximab PK: Confirmatory Serum Concentration [ Time Frame: Group D: Prior to Carboplatin Infusion, Cycle 1, Day 1 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• The participant has histologically or cytologically confirmed advanced solid tumor that is resistant to standard therapy or for which there is no standard therapy.
• The participant has measurable or non-measurable disease according to RECIST 1.0 guidelines.
• 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/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.
• If the participant has received prior therapy with platinum, the time to the first treatment of study drug from the last platinum exposure is >28 days.

Exclusion Criteria:

• 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,radiation 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 carboplatin.
• 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 I.V antibiotics), including tuberculosis.

Contacts and Locations

Locations

United States, Arkansas

Highlands Oncology Group

Fayetteville, Arkansas, United States, 72703

United States, Kansas

University of Kansas Medical Center

Fairway, Kansas, United States, 66205

United States, Oregon

Portland VA Medical Center

Portland, Oregon, United States, 91239

Oregon Health and Science University

Portland, Oregon, United States, 97239

United States, South Carolina

Medical University of South Carolina

Charleston, South Carolina, United States, 29425

United States, Texas

University of Texas MD Anderson Cancer Center

Houston, Texas, United States, 77030

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.

London, Ontario, Canada, N6A 4L6

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.

Montreal, Quebec, Canada, H3G 1A4

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

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT01063075
• Other Study ID Numbers: 13420; I4E-MC-JXBB ( Other Identifier: Eli Lilly and Company )
• First Posted: February 5, 2010
• Results First Posted: June 15, 2016
• Last Update Posted: September 26, 2019
• Last Verified: September 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)
• Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
• Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• URL: https://vivli.org/

Keywords provided by Eli Lilly and Company:

Cancer of Head; Cancer of Head and Neck; Cancer of Neck; Head and Neck Cancer; Head Cancer; Head Neoplasms; Head, Neck Neoplasms; Neck Cancer; Neck Neoplasms; Solid Neoplasm; Carcinoma; Sarcoma

Additional relevant MeSH terms:

Neoplasms; Carboplatin; Cetuximab; Antineoplastic Agents; Antineoplastic Agents, Immunological