Paclitaxel vs Paclitaxel + Cetuximab in Recurrent - Metastatic Head & Neck Carcinoma After Failure of a 1º Chemotherapy

Study Overview
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Brief Summary
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Treatment of recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC) after progression to first line EXTREME-type treatment in patients undergoing maintenance treatment with cetuximab.

Official Title
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Phase II, Randomized Clinical Trial to Assess the Efficacy of Paclitaxel vs Paclitaxel + Cetuximab in Subjects With Recurrent and/or Metastatic Squamous Head & Neck Carcinoma After Failure of a 1º Line Chemotherapy EXTREME Type Treatment

Conditions
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Head and Neck Cancer

Intervention / Treatment
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* Drug: Paclitaxel
* Drug: Cetuximab + Paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed the informed consent Age ≥ 18 and < 75 y ECOG (Eastern Cooperative Oncology Group)performance status: 0-1 Life expectancy of at least 12 weeks Histological or cytological confirmation of head & neck squamous cell carcinoma with localization in larynx, oropharynx, oral cavity or hypopharynx. Having received at least 2 cycles of EXTREME-type chemotherapy (cisplatin or carboplatin + fluoropyrimidines + cetuximab) and being in maintenance phase with cetuximab because of having reached CR (Complete response), PR (Partial response) or SD (Stable disease) to said treatment At least one measureable lesion by CT scan or MRI Adequate bone marrow, liver and kidney function, according to: Hb (Hemoglobin) ≥ 9.0 g/dl Platelets 100,000/mm3 ANC (Absolute Neutrophil Count) ≥ 1,500/mm3 Total bilirubin ≤ 2 times the UNL SGPT/ALT and SGOT/AST ≤ 3 x UNL (Upper normal limit) Alkaline phosphatase ≤ 2.5 x UNL Serum creatinine ≤ 1.5 times the ULN or creatinine clearance > 50 ml/min Adequate nutritional status: weight loss < 20% in relationship to usual weight or albumin ≥ 35 g/l, in the last 12 w Seric calcium adjusted to albumine lower or equal to 1,25 UNL. Toxicity, due to previous treatment received, resolved to grade 1, before enrolment in the study Women of childbearing potential should have a (-)ve pregnancy test in serum or urine,7 d before randomization. Postmenopausal women should have remained amenorrheic for at least 12 m. Furthermore, all men as well as women who participate in this study should use effective contraceptive methods beginning with the signing of the informed consent form and up to at least 6 m after the completion of the study or of the last dose, whichever occurs first Exclusion Criteria: Treatment for recurrent and/or metastatic disease other than the EXTREME- type first line (cisplatin or carboplatin + fluoropyrimidines + cetuximab) Non-measurable lesion as only evidence of disease Nasopharyngeal carcinoma Clinical or radiographic evidence of brain metastases Having history of or presenting clinically significant cardiovascular disease, such as, but not limited to, congestive heart failure, ≥ grade II of the NYHA, severe cardiac arrhythmias that require medication, or ≥ grade II peripheral vascular disease. Furthermore, those patients who have suffered myocardial infarction or unstable angina in the year prior to the onset of the study treatment or a recent onset angina in the last 3 m will also be excluded History of or current presence of grade >1 peripheral neuropathy History of active neurological disease History of uncontrolled convulsive episode Current ≥ 2 grade infection Known infection by HIV or chronic infection by HBV or HBC or presence of uncontrolled and severe intercurrent infections or other severe and uncontrolled concomitant diseases History of uncontrolled diabetes, uncontrolled HBP or hepatic condition. History of pulmonary fibrosis, acute pulmonary damage or interstitial pneumonia Any antineoplastic treatment within the 4 w prior to the randomization period History of another neoplastic disease during the last 5 y, with the exception of cured in situ basal cell ca.skin carcinoma, in situ ca.bladder, in situ ca.cervix and in situ ca.prostate Known allergy or suspicion of allergy or hypersensitivity to any component of cetuximab or paclitaxel Previous treatment with monoclonal antibodies or other signal transduction inhibitors or EGFR-targeted treatment (Except for previous treatment with cetuximab) Known drug abuse (exception Alcoholism) Any important and uncontrolled medical, psychological, psychiatric, geographic or social problem that may interfere in the participation of the subject in the study and that does not allow for adequate follow-up and compliance with the protocol and evaluation of the study results Women who are pregnant or in breast-feeding period Use of any investigational new drug within the 4 w prior to randomization

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Paclitaxel<br>Paclitaxel 80 mg/m2 may be infused, intravenously, every week. | Drug: Paclitaxel<br>* Paclitaxel 80 mg/m2 may be infused, intravenously, every week.<br>|
| Experimental: Cetuximab + Paclitaxel<br>Cetuximab 250 mg/m2 and Paclitaxel 80 mg/m2, both may be infused intravenously, every week. Cetuximab will be administered prior to paclitaxel. | Drug: Cetuximab + Paclitaxel<br>* Cetuximab 250 mg/m2 and Paclitaxel 80 mg/m2, both may be infused intravenously, every week. Cetuximab will be administered prior to paclitaxel.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | The primary endpoint was to select the most effective treatment arm based on the progression-free survival (PFS) reached in each treatment arm. This was defined as the time elapsed from inclusion in the study until the date when disease progression or death (for any cause) was documented. | Through study completion. The study was prematurely closed at 19 months due to lack of accrual. The primary endopoint was not analyzed. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Calculate overall survival (OS) in both arms | Through study completion. The study was prematurely closed at 19 months due to lack of accrual. The secondary endopoint was not analyzed. | 
| Percentage of Objective Response | Calculate the percentage of objective responses (OR), following the new RECIST criteria, obtained in both arms | Through study completion. The study was prematurely closed at 19 months due to lack of accrual. Neither the primary nor the secondary endopoints were analyzed. | 
| Participants With Adverse Events | To perform a descriptive analysis of the adverse events observed in the patients included in the study. Further analysis could not be performed due to early closure of this study due to lack of accrual. Adverse events were registered from study entry until 60 days after receiving the last dose of study drug. | The duration of the study (Nineteen months) and until the last patient included completed one year of follow up / died or was lost to FU. Adverse events were registered from study entry until 60 days after receiving the last dose of study drug. | 
| Treatment Compliance | Evaluate treatment compliance rate in both treatment arms, in order to analyze it, the dose intensity would be calculated as the quantity of each of the administered study drugs per unit of time (mg/m2/week) regardless of the treatment arm. To analyze the relative dose intensity, the dose of each administered drug will be divided per a unit of time and the planned quantity of each drug according to the doses described in the protocol. | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Head and Neck Cancer, Cetuximab, Erbitux, Paclitaxel, Extreme, Metastatic, Recurrent