Study in Advanced Solid Tumors

Study Overview
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Brief Summary
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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.

Official Title
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Phase 2 Study to Evaluate the Pharmacokinetics and Drug-Drug Interaction of Cetuximab and Cisplatin in Patients With Advanced Solid Tumors

Conditions
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Solid Tumor

Intervention / Treatment
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* Drug: Cetuximab
* Drug: Cisplatin
* Drug: 5 - Fluorouracil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The participant has histologically or cytologically 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. 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 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cetuximab and Cisplatin (D)<br>Cycle 1 (1 week, combination therapy): 400 milligrams per square meter (mg/m²) cetuximab administered (admin) intravenously (I.V) on week 1, day 1. 100 mg/m² cisplatin administered I.V on week 1, day 1. Optional 5- fluorouracil (FU) administered as a 96-hour continuous infusion (C.I.) of 1000 mg/m²/day (d) administered starting on week 1, day 1. After 1 cycle, participants may continue treatment as determined by the physician until progression of disease, unacceptable toxicity, or another withdrawal criterion is met. After protocol amendment February 2014, any newly enrolled participants will be placed into cetuximab and cisplatin (D) arm only. | Drug: Cetuximab<br>* Administered Intravenously<br>Drug: Cisplatin<br>* Administered Intravenously<br>Drug: 5 - Fluorouracil<br>* Administered Intravenously<br>|
| Experimental: Cetuximab and Cisplatin (C)<br>Cycle 1 (4 weeks, combination therapy): 100 mg/m² Cisplatin admin I.V on week 1, day 1. 5- FU admin as a 96-hour C.I. of 1000 mg/m²/d admin starting on week 1, day 1. 400 mg/m² cetuximab admin I.V on week 2, day 1. 250 mg/m² cetuximab admin I.V on week 3 and 4, day 1. Cycle 2-6 (3 weeks combination therapy): 100 mg/m² cisplatin admin I.V on week 1, day 1. 5- FU admin as a 96-hour C.I. of 1000 mg/m²/d admin starting on week 1, day 1. 250 mg/m² cetuximab admin I.V on week 1, 2, and 3, 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 were placed into cetuximab and cisplatin (C) arm only. After protocol amendment February 2014, any newly enrolled participants will be placed into cetuximab and cisplatin (D) arm only. | Drug: Cetuximab<br>* Administered Intravenously<br>Drug: Cisplatin<br>* Administered Intravenously<br>Drug: 5 - Fluorouracil<br>* Administered Intravenously<br>|
| Experimental: Cetuximab on Cisplatin (B)<br>Cycle 1: 400 mg/m² cetuximab admin I.V on week 1, day 1. 250 mg/m² cetuximab admin I.V on week 2 and 3, day 1. Cycle 2: 100 mg/m² cisplatin admin I.V on week 1, day 1. 5- FU admin as a 96-hour C.I. of 1000 mg/m²/d admin starting on week 1, day 1- 4. 250 mg/m² cetuximab admin I.V on week 1-3, day 1. Cycle 3 + : 100 mg/m² cisplatin admin I.V on week 1, day 1. 5- FU admin as a 96-hour C.I. of 1000 mg/m²/d admin starting on week 1, day 1-4. 250 mg/m² cetuximab admin I.V on week 1-3, 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 were placed into cetuximab and cisplatin (C) arm only. After protocol amendment February 2014, any newly enrolled participants will be placed into cetuximab and cisplatin (D) arm only. | Drug: Cetuximab<br>* Administered Intravenously<br>Drug: Cisplatin<br>* Administered Intravenously<br>Drug: 5 - Fluorouracil<br>* Administered Intravenously<br>|
| Experimental: Cisplatin on Cetuximab (A)<br>Cycle 1: 100 mg/m² cisplatin admin I.V on week 1, day 1. 5- FU admin as a 96-hour C.I. of 1000 mg/m²/d admin starting on week 1, day 1-4. 400 mg/m² cetuximab admin I.V on week 2, day 1. 250 mg/m² cetuximab admin I.V on week 3, day 1. Cycle 2 +: 100 mg/m² cisplatin admin I.V on week 1, day 1. 5- FU admin as a 96-hour C.I. of 1000 mg/m²/d admin starting on week 1, day 1-4. 250 mg/m² cetuximab admin I.V on weeks 1-3, 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 were placed into cetuximab and cisplatin (C) arm only. After protocol amendment February 2014, any newly enrolled participants will be placed into cetuximab and cisplatin (D) arm only. | Drug: Cetuximab<br>* Administered Intravenously<br>Drug: Cisplatin<br>* Administered Intravenously<br>Drug: 5 - Fluorouracil<br>* Administered Intravenously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Cisplatin Pharmacokinetics (PK): Area Under the Concentration (AUC) Versus Time Curve From Time Zero to Infinity (AUC[0-∞]) |  | Groups A and C: Cycle 1,Day 1 and Cycle 2 Day 1; Baseline (Prior to Cisplatin Infusion), 1, 1.50, 2, 3, 5, 8, 24, 72 hours (After the Start of Cisplatin Infusion). | 
| Cetuximab Pharmacokinetics: Area Under the Concentration Versus Time Curve During One Dosing Interval at Steady State (AUC τ,ss) |  | Group B:Cycle 1,Day 15 and Cycle 2, Day 1 and Group C: Cycle 1, Day 22 and Cycle 2, Day 1: Baseline (Prior to Cetuximab Infusion),1, 2, 4, 8, 24, 72, 120, and 168 hours (After the Start of Cetuximab Infusion). | 
| Total Cisplatin Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) |  | Groups A and C: Cycle 1,Day 1 and Cycle 2 Day 1; Baseline (Prior to Cisplatin Infusion), 1, 1.50, 2, 3, 5, 8, 24, 72 hours (After the Start of Cisplatin Infusion). | 
| Cetuximab Pharmacokinetics: Maximum Observed Plasma Concentration at Steady State (Cmax,ss) |  | Group B:Cycle 1,Day 15 and Cycle 2, Day 1 and Group C: Cycle 1, Day 22 and Cycle 2, Day 1: Baseline (Prior to Cetuximab Infusion),1, 2, 4, 8, 24, 72, 120, and 168 hours (After the Start of Cetuximab Infusion). | 
| Total Cisplatin Pharmacokinetics: Measurement of the Time After Administration When the Maximum Plasma Concentration is Reached (Tmax) |  | Groups A and C: Cycle 1,Day 1 and Cycle 2 Day 1; Baseline (Prior to Cisplatin Infusion), 1, 1.50, 2, 3, 5, 8, 24, 72 hours (After the Start of Cisplatin Infusion). | 
| Cetuximab Pharmacokinetics: Measurement of the Time After Administration When the Maximum Plasma Concentration is Reached (Tmax) |  | Group B:Cycle 1,Day 15 and Cycle 2, Day 1 and Group C: Cycle 1, Day 22 and Cycle 2, Day 1: Baseline (Prior to Cetuximab Infusion),1, 2, 4, 8, 24, 72, 120, and 168 hours (After the Start of Cetuximab Infusion). | 
| Cetuximab Pharmacokinetics: Confirmatory Serum Concentration |  | Group D:Cycle 1, Day 1: Prior to Cisplatin Infusion. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sarcoma, Cancer of Head, Cancer of Head and Neck, Cancer of Neck, Cancer of the Head, Cancer of the Head and Neck, Cancer of the Neck, Head and Neck Cancer, Head Cancer, Head Neoplasms, Head, Neck Neoplasms, Neck Cancer, Neck Neoplasms, Solid Neoplasm, Carcinoma