To assess the efficacy of combined treatment with sorafenib and metformin.
ID
Source
Brief title
Condition
- Respiratory and mediastinal neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Non Progressive Rate (NPR) after 6 weeks of treatment
Secondary outcome
Response Rate, duration of Response, Progression Free Survival and Overall
survival
Background summary
The overall survival in lung cancer patients is poor and chemotherapy treatment
has reached a plateau to improve survival. Recently, metformin is discovered as
an anti cancer agent. Metformin is known as a save drug, with minor toxicity
and used in treatment of type II diabetes for more than 40 years. Preclinical
studies have found that metformin has anti cancer properties by targeting mTOR,
an effector in the PI3K pathway. Sorafenib is a multitarget tyrosine kinase
inhibitor and is registered for second line treatment in renal cell and
hepatocellular cancer. In non-small cell lung cancer (NSCLC), sorafenib is
currently tested in phase III studies. Sorafenib targets Raf kinase, which is
part of the Ras/Raf pathway. This pathway is overactive in patients harbouring
a K-Ras mutation.The PI3K pathway and the Ras/Raf pathway have a close
interaction and are both important stimulants for cell growth and
proliferation. In this study we will treat patients with metformin and
sorafenib. We hypothesize that metformin wil enhance the efficacy of
sorafenib.
Study objective
To assess the efficacy of combined treatment with sorafenib and metformin.
Study design
An open label, multicenter, phase II study.
Intervention
treatment with sorafenib and metformin
Study burden and risks
Nature and extent of the burden and risks associated with participation,
benefit and group relatedness: Sorafenib is previously tested in lung cancer
patients and is found to be effective and tolerable. Metformin is a save and
frequently prescribed drug used as first choice of treamtment for patients
with type II diabetes mellitus. The frequency of tumor assessment using CT and
blood samples is similar as by standard treatment.
de boelelaan 1117
Amsterdam 1081 HV
NL
de boelelaan 1117
Amsterdam 1081 HV
NL
Listed location countries
Age
Inclusion criteria
1. Histologically advanced NSCLC stage IIIB or IV harbouring a K-RAS mutation 2. Disease progression after at least 1 prior chemotherapy regimen that should include a platinum doublet 3. Prior surgery and/or localized irradiation is permitted provided that the irradiated lesion is not the only measurable lesion. 4. Age > 18 years. 5. ECOG Performance Status of 0-2 6. Life expectancy of at least 12 weeks 7. written informed consent
Exclusion criteria
1. History of cardiac disease: congestive heart failure >NYHA class 2; active CAD (MI more than 6 mo prior to study entry is allowed); cardiac arythmias requiring anti-arythmic therapy( beta blockers or digoxin are permitted) or uncontrolled hypertension. 2. History of HIV infection or chronic hepatitis B or C. 3. Active clinically serious infections (> grade 2 NCI-CTC version 3.0) 4. Symptomatic metastatic brain or meningeal tumors (unless the patient is > 1 months from definitive radiotherapy and off steroids): 5. Patients with seizure disorder requiring medication (such as steroids or anti-epileptics)
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2011-004683-30-NL |
| CCMO | NL38229.029.11 |