Metformin Plus Paclitaxel for Metastatic or Recurrent Head and Neck Cancer (METTAX)

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

Metformin plus paclitaxel for recurrent or metastatic head and neck cancer: a randomized phase II trial

Study Overview

• Status: Terminated
• Conditions: Head and Neck Neoplasms; Squamous Cell Carcinoma
• Intervention / Treatment: Drug: placebo; Drug: paclitaxel 175mg/m² q21d; Drug: metformin up to 2500mg/d

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.

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • SP
    • Barretos, SP, Brazil, 14784400
      • Barretos Cancer Hospital

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

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

Collaborators and Investigators

• Sponsor: Lucas Vieira dos Santos
• Collaborators: Fundação de Amparo à Pesquisa do Estado de São Paulo; University of Campinas, Brazil
• Investigators: Principal Investigator: Lucas V dos Santos, MD, HCB; Study Chair: Jose BC Carvalheira, MD, PhD, University of Campinas, Brazil; Study Director: Andre L. Carvalho, MD, PhD, HCB

Study record dates

Study Major Dates

• Study Start: February 1, 2011
• Primary Completion (Actual): January 1, 2014
• Study Completion (Actual): April 1, 2014

Study Registration Dates

• First Submitted: April 5, 2011
• First Submitted That Met QC Criteria: April 11, 2011
• First Posted (Estimate): April 12, 2011

Study Record Updates

• Last Update Posted (Estimate): January 27, 2015
• Last Update Submitted That Met QC Criteria: January 26, 2015
• Last Verified: January 1, 2015

More Information

Terms related to this study

• Keywords: paclitaxel; metformin; head and neck cancer; squamous cell carcinoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Squamous Cell; Neoplasms; Head and Neck Neoplasms; Carcinoma, Squamous Cell; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel; Metformin
• Other Study ID Numbers: METTAX200901