Cervical CancerPhase 2METOXY-LACCNCT04275713
Altered Tumor Oxygenation by Metformin, a Potential Step in Overcoming Radiotherapy Resistance in LACC
A Phase 2 study testing Metformin and Cisplatin in people with Cervical Cancer, run by Oslo University Hospital at 1 site in Norway.
Trial summary
Poor tumor oxygenation (hypoxia) is an established negative prognostic and predictive factor in locally advanced cervical cancer (LACC). Hypoxia-modifying measures implemented in the clinic are lacking. Metformin is a well-known, well-tolerated and low-cost drug used for decades in the treatment of type 2- diabetes. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Cervical Cancer
- What is being tested?
- Metformin and Cisplatin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 1 siteNorway
- Study dates
- 22 May 2020to 8 Nov 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed cervical cancer (squamous cell carcinoma, adenocarcinoma and adenosquamous carcinoma)
- Planned for radical chemoradiotherapy
- Over 18 years
- Speaks and understands Norwegian
- ECOG 0-1
- Cervical tumor available for biopsy by gynecological examination
Show all 14Show fewer
- Hemoglobin ≥ 9 g/dL (blood transfusions are allowed)
- Leukocytes ≥ 3,5 x 10^9/L 18
- Absolute neutrophil count ≥ 1,5 x 10^9/L
- Platelets ≥ 100 x 10^9/L
- Total bilirubin ≤ 25 umol/L
- AST/ALT ≤ 2,5 x institutional upper limit
- Creatinine ≤ 90 or creatinine clearance ≥ 60 ml/min/1.73m2 Patients with elevated creatinine secondary to hydronephrosis may be eligible if renal function returns to normal after inserting an internal stent or nephrostomy
- Women of childbearing potential (WOCBP) should have a negative highly sensitive serum pregnancy test within 72 hours prior to receiving the first dose of study medication.
Who cannot join
- Evidence of distant metastasis. Suspicious paraaortic lymph nodes below the renal vessel are 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
Show all 16Show fewer
- Contraindications such as
- Hypersensitivity to the active substance or to any of the excipients listed Section 6.1.
- Severe renal failure (GFR <30 ml / min).
- Acute conditions leading to the risk of renal impairment, eg: dehydration, severe infectious conditions, shock.
- Disease that can cause tissue hypoxia (especially acute illness or exacerbation of chronic illness), such as: acute decompensated heart failure, lung failure, recent heart attack, shock.
- Liver failure, acute alcohol intoxication, alcoholism.
- 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
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Altered Tumor Oxygenation by Metformin, a Potential Step in Overcoming Radiotherapy Resistance in Locally Advanced Cervical Cancer.
Poor tumor oxygenation (hypoxia) is an established negative prognostic and predictive factor in locally advanced cervical cancer (LACC). Hypoxia-modifying measures implemented in the clinic are lacking.
Metformin is a well-known, well-tolerated and low-cost drug used for decades in the treatment of type 2- diabetes. Recent studies suggest an improved tumor oxygenation by metformin potentially improving radiotherapy response and patient outcome.
Read more
This study is a randomized, phase II, open label study in patients with LACC where patients are randomized to standard cisplatin-based chemoradiotherapy +/- Metformin.
Metformin will be started one week prior to the start of chemoradiotherapy, and will be continued throughout the entire radiation treatment.
Tumor oxygenation will be evaluated by gene signatures and MRI- parameters.
- Conditions
- Cervical Cancer
- Medical subject headings
- Uterine Cervical Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetforminDrug
Metformin is an oral antidiabetic drug
CisplatinDrug
Cisplatin 40 mg/m2 given intravenously once a week, maximum 6 cycles
| Study group | Role | What they receive |
|---|---|---|
| Standard Chemoradiotherapy +/- metformin | Experimental | Metformin will be given orally at doses of 850 mg twice a day. Metformin will be started one week prior to the start of standard cisplatin-based chemoradiotherapy, and will be continued throughout the entire radiation treatment Receives: Drug: Metformin; Drug: Cisplatin |
| Standard chemoradiotherapy | Active comparator | Standard chemoradiotherapy is given as a combination of EBRT and IGT:
* 45 Gy in 1.8 Gy/fraction to the pelvis/abdomen, 5 fractions/week
* 55-57.5 Gy in 2.2-2.3 Gy/fraction to pathological lymph nodes as a simultaneously integrated boost (SIB)
* 4 fractions of brachytherapy, 7.8 Gy/fraction, to the cervix
* Concomitant Cisplatin weekly during the external beam radiotherapy (EBRT) Receives: Drug: Cisplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Metformin dependent changes in hypoxia-related gene expression.
- A hypoxia related 6-gene expression signature analyzed by RNA-sequencing will be obtained before and after one week of metformin
- The signature consist of the following six genes: ERO1A, DDIT3, KCTD11, P4HA2, STC2, UPK1A
Measured: baseline and one week
Secondary outcomes (3)
Metformin dependent changes in MRI-parameters.
- Diffusion-weighted MRI and Dynamic Contrast-Enhanced MRI will be obtained before and after one week of metformin.
- Hypoxic tumor fraction on MRI will be calculated using the combined information from DWI- and DCE-MRI
Measured: baseline and one week
Metformin dependent change in acute toxicity
- Physician-reported acute toxicity will be assessed with validated questionnaires (CTCAE version 3 and 4).
Measured: baseline, 4 weeks, end of treatment (about 7 weeks), 3 month follow-up
Metformin dependent change in tumor volume during treatment
- Tumor volume will be measured on T2W-MRI before the start of treatment and at the first fraction of brachytherapy
Measured: Baseline and about 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2020
- Study start22 May 2020
- Primary completion11 Jun 2024
- Study completion8 Nov 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cervical CancerStudies of the same condition, open and under way.
- More trials run by Oslo University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Patients are randomized to intervention Group (metformin in combination with radiotherapy) or standard of care.
- Masking
- None (open label)
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- Oslo University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kjersti Bruheim, Oslo University Hospital
- Investigators
- Kjersti Bruheim, PhD, Principal investigator, Oslo University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04275713
- Sponsor's protocol ID
- METOXY-LACC
- Acronym
- METOXY-LACC
- Status last verified
- Dec 2024
- First submitted
- 12 Feb 2020
- Last updated
- 20 Jan 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Altered Tumor Oxygenation by Metformin, a Potential Step in Overcoming Radiotherapy Resistance in Locally Advanced Cervical Cancer.
- ClinicalTrials.gov ID
- NCT04275713
- Acronym / sponsor ID
- METOXY-LACC / METOXY-LACC
- Conditions
- Cervical Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 41 participants (actual)
- Lead sponsor
- Oslo University HospitalUniversity, hospital or other
- Study start
- 22 May 2020 (actual)
- Primary completion
- 11 Jun 2024 (actual)
- Study completion
- 8 Nov 2024 (actual)
- First posted
- 19 Feb 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Poor tumor oxygenation (hypoxia) is an established negative prognostic and predictive factor in locally advanced cervical cancer (LACC). Hypoxia-modifying measures implemented in the clinic are lacking.
Metformin is a well-known, well-tolerated and low-cost drug used for decades in the treatment of type 2- diabetes. Recent studies suggest an improved tumor oxygenation by metformin potentially improving radiotherapy response and patient outcome.
This study is a randomized, phase II, open label study in patients with LACC where patients are randomized to standard cisplatin-based chemoradiotherapy +/- Metformin.
Metformin will be started one week prior to the start of chemoradiotherapy, and will be continued throughout the entire radiation treatment.
Tumor oxygenation will be evaluated by gene signatures and MRI- parameters.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Patients are randomized to intervention Group (metformin in combination with radiotherapy) or standard of care.
| Arm | Type | Receives |
|---|---|---|
| Standard Chemoradiotherapy +/- metformin | Experimental | Drug: Metformin, Drug: CisplatinMetformin will be given orally at doses of 850 mg twice a day. Metformin will be started one week prior to the start of standard cisplatin-based chemoradiotherapy, and will be continued throughout the entire radiation treatment |
| Standard chemoradiotherapy | Active comparator | Drug: CisplatinStandard chemoradiotherapy is given as a combination of EBRT and IGT: * 45 Gy in 1.8 Gy/fraction to the pelvis/abdomen, 5 fractions/week * 55-57.5 Gy in 2.2-2.3 Gy/fraction to pathological lymph nodes as a simultaneously integrated boost (SIB) * 4 fractions of brachytherapy, 7.8 Gy/fraction, to the cervix * Concomitant Cisplatin weekly during the external beam radiotherapy (EBRT) |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Histologically confirmed cervical cancer (squamous cell carcinoma, adenocarcinoma and adenosquamous carcinoma)
Key exclusion criteria (16 listed)
- Evidence of distant metastasis. Suspicious paraaortic lymph nodes below the renal vessel are 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MetforminMetformin is an oral antidiabetic drug | Drug | Standard Chemoradiotherapy +/- metformin |
| CisplatinCisplatin 40 mg/m2 given intravenously once a week, maximum 6 cycles | Drug | Standard Chemoradiotherapy +/- metformin, Standard chemoradiotherapy |
Primary outcome
Metformin dependent changes in hypoxia-related gene expression.
Time frame: baseline and one week
* A hypoxia related 6-gene expression signature analyzed by RNA-sequencing will be obtained before and after one week of metformin * The signature consist of the following six genes: ERO1A, DDIT3, KCTD11, P4HA2, STC2, UPK1A
3 secondary outcomes
Metformin dependent changes in MRI-parameters.
Time frame: baseline and one week
Metformin dependent change in acute toxicity
Time frame: baseline, 4 weeks, end of treatment (about 7 weeks), 3 month follow-up
Metformin dependent change in tumor volume during treatment
Time frame: Baseline and about 4 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jan 2025.
- Individual participant dataSharing planned: No
Related trials for Cervical Cancer
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingObservational study
Proton Re-irradiation in Patients With Recurrent or Second Primary Head and Neck Cancer , a Multicentre Phase II Single Arm Trial
Head & Neck Cancer
RecruitingPhase 2/3
Multicenter Validation Trial of [18F]AlF-FAPI-74 for PET Imaging of Cancer-associated Fibroblasts Through Fibroblast Activation Protein Inhibitors (FAPI) in Different Tumor Types
Oesophageal Cancer, Gastric Cancer
RecruitingPhase 2
Proton Spatially Fractionated Radiotherapy or Photon Stereotactic Body Radiotherapy in Combination With Pembrolizumab Before Surgery for the Treatment of Locally Advanced and Radiation-Naive Locoregionally Recurrent Oral Cavity Cancer, OSPRI Trial
Locally Advanced Oral Cavity Squamous Cell Carcinoma, Locally Recurrent Oral Cavity Squamous Cell Carcinoma
RecruitingPhase 4
Lidocaine Infiltration and Neuroimmunomodulation in Head and Neck Cancer Surgery
Head and Neck Cancer (H&N)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kjersti Bruheim, PhD principal investigator
Oslo University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Metformin and Cisplatin in people with Cervical Cancer, run by Oslo University Hospital at 1 site in Norway.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Norway. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Metformin dependent changes in hypoxia-related gene expression. (time frame: baseline and one week). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jan 2025.