Locally advanced cervical cancer MedDRA version: 20.0 Level: LLT Classification code 10008229 Term: Cervical cancer System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Glucophage
Product Name: Glucophage
Pharmaceutical Form: Tablet
Trade Name: Cisplatin Accord
Product Name: Cisplatin Accord
Pharmaceutical Form: Concentrate for solution for infusion
Sponsors
Oslo University Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •Histologically confirmed cervical cancer (squamous cell carcinoma, adenocarcinoma and adenosquamous carcinoma) •Planned for radical chemoradiotherapy •Included in the MIMB-protocol •Over 18 years •Speaks and understands Norwegian •ECOG 0-1 •Cervical tumor available for biopsy by gynecological examination •Able to receive weekly cisplatin •Able to take oral medication •Ability to understand and willing to sign a written informed consent •Willing to undergo biopsies of cervical tumor •Willing to be included in the Embrace 2- protocol if randomized to the control group •Negative pregnancy test in women with childbearing potential •Normal bone marrow and organ function = 14 days before inclusion Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 45 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 45
Exclusion criteria
Exclusion criteria: •Evidence of distant metastasis. Suspicious paraaortic lymphnodes below the renal wessel is allowed if they are covered by the radiation field •Patients who have received other cancer treatments for their cervical cancer •Patients who receive other experimental drugs •Known diabetes mellitus •Currently taking Metformin or any other antidiabetic drugs (sulfonylureas, thiazolidinediones, insulin) •History of allergic reaction attributed to compounds of similar chemical or biologic composition to metformin •Any condition associated with increased risk of metformin- induced lactic acidosis (congestive heart failure defined as New York Heart Association (NYHA) class III or IV functional status, history of acidosis of any kind) •Uncontrolled intercurrent somatic illness including, but not limited to, ongoing or active serious infections, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, myocardial infarction within 6 months and cerebrovascular disease with previous stroke •Psychiatric illness /social situations limiting study compliance •Prior radiotherapy to the pelvis •Already on medication with increased risk of lactic acidosis •Patients who are pregnant or breastfeeding are excluded due to risk of teratogenic and abortifacient effects of radiotherapy and cisplatin, and the potential risk of adverse effect of nursing infants •Patients with other invasive malignancies except non-melanoma skin cancers •Known HIV-positive patients on antiretroviral therapy •Known conditions limiting absorption of study drug (bowel obstruction, malabsorption syndromes) •Patients taking the drug disulfiram (antabus)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The overall study objective is to investigate whether metformin can induce molecular changes, cell death and/or improved oxygenation in the tumor tissue, especially in hypoxic areas, and thereby improve tumor response with acceptable added acute toxicity. ;Secondary Objective: Not applicable;Primary end point(s): To determine if one week of metformin treatment can change tumor hypoxia-related gene expression signature;Timepoint(s) of evaluation of this end point: Evaluated after one week of metformin prior to start of chemoradiotherapy. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. To detect changes in tumor cell density, extracellular space, vascularity and hypoxia evaluated by DW- and DCE-MRI after one week of metformin before start of chemoradiotherapy. 2. To determine if metformin- treated patients have increased tumor shrinkage during external radiation treatment, estimated by the percentage decrease in tumor volume on T2W- and DW-MRI at the time of brachytherapy. 3. To determine acute toxicity following metformin and chemoradiotherapy. ;Timepoint(s) of evaluation of this end point: 1. After one week of metformin prior to start of chemoradiotherapy. 2. At the time of brachytherapy. 3. Ongoing | — |
Countries
Norway
Contacts
Public ContactTrial Manager
Oslo University Hospital
Outcome results
None listed