Metformin Plus Paclitaxel for Metastatic or Recurrent Head and Neck Cancer

Study Overview
=================
Brief Summary
-----------------
Metformin plus paclitaxel for recurrent or metastatic head and neck cancer: a randomized phase II trial

Detailed Description
-----------------
METTAX is a phase II randomized trial that aim to evaluate the addition of metformin to paclitaxel in patients that failed to curative-intent treatment for Head-and neck neoplasms. Patients eligible for this protocol will be randomized to paclitaxel 175mg/m2 plus metformin or placebo until disease progression or unacceptable toxicity. The primary end-point is disease control (complete response, partial response or stable disease, according to RECIST 1.1) in the 12th week. Secondary end-points are PFS, OS, response rate and safety. Molecular markers in samples collected before and under treatment will be tested for correlation with clinical outcomes.

Official Title
-----------------
Randomized Phase II Study of Paclitaxel Plus Metformin or Placebo for the Treatment of Platinum-refractory, Recurrent or Metastatic Head and Neck Neoplasms

Conditions
-----------------
Head and Neck Neoplasms, Squamous Cell Carcinoma

Intervention / Treatment
-----------------
* Drug: metformin up to 2500mg/d
* Drug: paclitaxel 175mg/m² q21d
* Drug: placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 18 years or older Biopsy-proven head and neck squamous cell carcinoma Ineligibility for curative intent therapy, e.g., surgery or radiation therapy recurrent or stage IV disease previous failure to platinum-based chemotherapy measurable disease according to RECIST v1.1 PS ECOG 0-2 Exclusion Criteria: known hypersensitivity to metformin or paclitaxel SNC metastasis Acute or chronic infection

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Paclitaxel, placebo<br>Paclitaxel 175mg/m² q21d until disease progression, unacceptable toxicity or consent withdrawal | Drug: paclitaxel 175mg/m² q21d<br>* paclitaxel 175mg/m² q21d<br>* Other names: taxol;Drug: placebo<br>* placebo<br>|
| Experimental: Paclitaxel plus metformin<br>Paclitaxel 175mg/m² q21d + metformin up to 2500mg/d until disease progression, prohibitive toxicity or consent withdrawal | Drug: metformin up to 2500mg/d<br>* metformin up to 2500mg/d<br>* Other names: Glifage;Drug: paclitaxel 175mg/m² q21d<br>* paclitaxel 175mg/m² q21d<br>* Other names: taxol;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease control at week 12 | Number of subjects at week 12 with complete response, partial response or stable disease, over the total number of subjects, for each arm. Disease control means complete response, partial response or stable disease, according to RECIST 1.1. | 12th week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | We will measure the number of subjects without progressive disease (complete response, partial response or stable disease) 6mo after the start of therapy, also after 1 and 2 years from the start of therapy. PFS will also be analysed with log-rank test, and reported as HR with respective 95% CI and p value, and median PFS will be estimated with kaplan-meyer method. All calculations will be performed 6 months after the last patient recruited. Also, the survival rate at year one and two will be calculated. | 6mo after the last patient recruited | 
| Overall Survival (subjects without death (any cause)) | We will measure the number of subjects without death (any cause) 6mo after the start of therapy, and also after 1 and 2 years from the start of therapy. OS will also be analysed with log-rank test, and reported as HR with respective 95% CI and p value, and median OS will be estimated with kaplan-meyer method. All calculations will be performed 6 months after the last patient recruited. Also, the survival rate at year one and two will be calculated. | 6mo after the last enrolled patient | 
| Number of patients with Grade 3-5 Adverse Events in each arm, for each category of AE | Safety and tolerability will be assessed using NCI CTCAE v3. The number of patients in each arm experiencing grade 3-5 AE (for each AE) over the total number of subjects will be measured, and the proportion of patients experiencing AE in each arm will be compared using uncorrected chi-sq test. AE will be recorded in baseline and in each visit, and the worst grade AE will be considered. | 6 mo after the last enrolled patients | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
head and neck cancer, paclitaxel, metformin, squamous cell carcinoma