Rectal NeoplasmsPhase 2NEOMETRENCT02473094
Neoadjuvant Metformin in Association to Chemoradiotherapy for Locally Advanced Rectal Cancer
A Phase 2 study testing Capecitabine, Metformin and Radiotherapy in people with Rectal Neoplasms and Adenocarcinoma, run by University of Campinas, Brazil at 1 site in Brazil.
Trial summary
A phase II, randomized study of placebo versus metformin in association to chemotherapy with capecitabine and radiation in the neoadjuvant treatment of locally advanced (T3-4N0M0 or TxN1-2M0) rectal carcinomas. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rectal Neoplasms, Adenocarcinoma, Carcinoma
- What is being tested?
- Capecitabine, Metformin and Radiotherapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 3 participants
- Where
- 1 siteBrazil
- Study dates
- Jul 2015to Feb 2016
- 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
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 18 years or older;
- biopsy proven poorly differentiated carcinoma or adenocarcinoma of the rectum;
- lesions located within 12 cm of the anal verge (from colonoscopy assessment);
- ability to tolerate oral treatment;
- locally advanced tumor, classified by the presence of positive regional lymph nodes or primary tumor invasion beyond the serosa (T3 or T4), assessed by MRI;
- eligibility for curative surgery (no distant metastasis or invasion of bony structures of the pelvis);
- Performance Status (PS) Eastern Cooperative Oncology Group (ECOG) 0-2;
- adequate hematologic functions (hemoglobin ≥ 10 g / dL [5.6 mmol / L]; neutrophil count ≥ 1,500 / mm3 and platelet count ≥ 100,000 / mm3), adequate renal function (serum creatinine less than 1.5 times the UNL) and adequate hepatic function (bilirubin less than 1.5 times the UNL; aspartate aminotransferase and alanine aminotransferase less than 2.5 times the UNL);
Who cannot join
- known hypersensitivity to metformin or its excipients;
- squamous carcinomas of the rectum or anal canal;
- chronic treatment with corticosteroids or other immunosuppressive agents;
- treatment with oral antidiabetic products;
- distant metastasis at diagnosis or tumor invasion of pelvic bone structures that may proscribe curative intent surgery;
- chronic or acute infections;
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- use of drugs under study up to four weeks prior to randomization;
- pregnant or nursing patients;
- prior radiotherapy to the pelvic region;
- myocardial infarction up to six months prior to randomization, or uncontrolled ischemic heart disease;
- congestive heart insufficiency New York Heart Association (NYHA) III-IV.
Trial locations and contacts
1 site in 1 country.
Brazil1 site
Clinical Oncology Department - General Hospital - State University of Campinas (UNICAMP)
Campinas, São Paulo, 13083888
About this study
Official title: Metformin in Association to Chemoradiotherapy for the Neoadjuvant Treatment of Locally Advanced Rectal Cancer: a Randomized, Placebo-controlled Phase II Study
A phase II, randomized study of placebo versus metformin in association to chemotherapy with capecitabine and radiation in the neoadjuvant treatment of locally advanced (T3-4N0M0 or TxN1-2M0) rectal carcinomas.
Read the detailed description
NEOMETRE is a randomized, double blind trial aiming to evaluate the efficacy and tolerability of metformin in association to chemoradiotherapy for the preoperative treatment of locally advanced (T3-4N0M0 or TxN1-2M0) rectal carcinomas.
Patients eligible for this study will be submitted to neoadjuvant 3D radiotherapy with 50,4 Gray (Gy) divided in 25 applications, in association to capecitabine, 825mg/m2 bid for five days every week. The participants will be randomized to daily metformin or placebo during the chemoradiotherapy period. The primary end-point is pathological complete response. The secondary end-points are recurrence-free survival (RFS), disease-free survival (DFS), overall survival (OS), local recurrence rate, overall response rate, sphincter preservation rate, quality of life (QoL) and toxicity.
- Conditions
- Rectal Neoplasms, Adenocarcinoma, Carcinoma
- Being tested
- Capecitabine, Metformin, Radiotherapy, Placebo
- Keywords
- Metformin, Rectal Cancer, Rectum, Radiotherapy, Capecitabine, Neoadjuvant, Adenocarcinoma, Carcinoma
- Medical subject headings
- Rectal Neoplasms, Adenocarcinoma, Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CapecitabineDrug
Also called Xeloda
Capecitabine 825mg/m2 bid, D1-D5 q7d
MetforminDrug
Also called Glifage, Dimefor, Glucoformin, Glucophage
Metformin up to 2500mg/d
RadiotherapyRadiation
Also called RDT
3D radiotherapy 50,4Gy divided in 25 fractions
PlaceboDrug
Placebo up to 2500mg/d
| Study group | Role | What they receive |
|---|---|---|
| Neoadjuvant capecitabine and metformin | Experimental | * Capecitabine 825 mg/m2 bid D1-5, q7d, for five weeks;
* Metformin 2500mg/d for five weeks;
* 3D radiotherapy 50,4Gy divided in 25 fractions Receives: Drug: Capecitabine; Drug: Metformin; Radiation: Radiotherapy |
| Neoadjuvant capecitabine and placebo | Placebo comparator | * Capecitabine 825 mg/m2 bid D1-5, q7d, for five weeks;
* Placebo 2500mg/d for five weeks;
* 3D radiotherapy 50,4Gy divided in 25 fractions Receives: Drug: Capecitabine; Radiation: Radiotherapy; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pathological Complete Response
Pathological evaluation of the surgical specimen. Complete response will be defined as absence of neoplastic tissue upon pathological exam.
Measured: 8 to 16 weeks after neoadjuvant treatment completion
Secondary outcomes (8)
Overall Response Rate
Magnetic Resonance Imaging (MRI) assessment to compare the response of chemoradiotherapy+metformin versus chemoradiotherapy+placebo.
Measured: 4 to 6 weeks after neoadjuvant treatment completion
Sphincter Preservation Rate
Rate of anal sphincter preservation during curative intent surgery.
Measured: 8 to 16 weeks after neoadjuvant treatment completion
Toxicity will be assessed using National Cancer Institute Common Toxicity Criteria for Adverse Effects (NCI CTCAE) v4.03
Safety and tolerability will be assessed using National Cancer Institute Common Toxicity Criteria for Adverse Effects (NCI CTCAE) v4.03. The number of patients in each arm experiencing grade 3-5 adverse events ou 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-square test. AE will be recorded in baseline and in each visit, and the worst grade AE will be considered.
Measured: up to 4 weeks after neoadjuvant treatment completion
Local Recurrence Rate
Rate of local or pelvic recurrence during follow up.
Measured: up to 5 years
Local Recurrence Free Survival
The number of subjects without local relapse will be measured 6mo after the start of therapy, also after 1, 3 and 5 years from the start of therapy. Local recurrence free survival will be analysed with log-rank test, and reported as Hazard Ratio (HR) with respective 95% Confidence Interval (CI) and p value, and its median value will be estimated with kaplan-meyer method.
Measured: up to 5 years
Disease Free Survival
The number of subjects without relapse will be measured 6mo after the start of therapy, also after 1, 3 and 5 years from the start of therapy. Disease free survival will be analysed with log-rank test, and reported as HR with respective 95% CI and p value, and its median value will be estimated with kaplan-meyer method.
Measured: up to 5 years
Overall Survival
The number of subjects without death (any cause) will be measured 6mo after the start of therapy, and also after 1, 3 and 5 years from the start of therapy. Overall survival 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, three and five will be calculated.
Measured: up to 5 years
Quality of Life
European Organization for Research and Treatment of Cancer Quality of Life Questionaire (EORTC QLQ)-C30 and EORTC QLQ-CR29 will be assessed on screening, at the last day of neoadjuvant treatment, 4 weeks after neoadjuvant treatment completion and up to 4 weeks after surgery.
Measured: up to 20 weeks after neoadjuvant treatment completion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jun 2015 (estimated)
- Study startJul 2015
- Primary completionFeb 2016
- Study completionFeb 2016
Why it stopped: Slow Accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Rectal NeoplasmsStudies of the same condition, open and under way.
- 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
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Campinas, Brazil
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ligia Traldi Macedo, University of Campinas, Brazil
- Investigators
- Ligia T Macedo, MD, Principal investigator, Clinical Oncology Department, State University of Campinas (UNICAMP)Jose BC Carvalheira, MD, PhD, Study chair, Clinical Oncology Department, State University of Campinas (UNICAMP)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02473094
- Sponsor's protocol ID
- NEOMETRE201501
- Acronym
- NEOMETRE
- Status last verified
- Nov 2017
- First submitted
- 13 Jun 2015
- Last updated
- 28 Nov 2017
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Metformin in Association to Chemoradiotherapy for the Neoadjuvant Treatment of Locally Advanced Rectal Cancer: a Randomized, Placebo-controlled Phase II Study
- ClinicalTrials.gov ID
- NCT02473094
- Acronym / sponsor ID
- NEOMETRE / NEOMETRE201501
- Conditions
- Rectal Neoplasms, Adenocarcinoma, Carcinoma
- Keywords
- Metformin, Rectal Cancer, Rectum, Radiotherapy, Capecitabine, Neoadjuvant, Adenocarcinoma, Carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow Accrual
- Enrolment
- 3 participants (actual)
- Lead sponsor
- University of Campinas, BrazilUniversity, hospital or other
- Study start
- Jul 2015
- Primary completion
- Feb 2016 (actual)
- Study completion
- Feb 2016 (actual)
- First posted
- 16 Jun 2015 (estimated)
- 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.
A phase II, randomized study of placebo versus metformin in association to chemotherapy with capecitabine and radiation in the neoadjuvant treatment of locally advanced (T3-4N0M0 or TxN1-2M0) rectal carcinomas.
Detailed description
NEOMETRE is a randomized, double blind trial aiming to evaluate the efficacy and tolerability of metformin in association to chemoradiotherapy for the preoperative treatment of locally advanced (T3-4N0M0 or TxN1-2M0) rectal carcinomas.
Patients eligible for this study will be submitted to neoadjuvant 3D radiotherapy with 50,4 Gray (Gy) divided in 25 applications, in association to capecitabine, 825mg/m2 bid for five days every week. The participants will be randomized to daily metformin or placebo during the chemoradiotherapy period. The primary end-point is pathological complete response. The secondary end-points are recurrence-free survival (RFS), disease-free survival (DFS), overall survival (OS), local recurrence rate, overall response rate, sphincter preservation rate, quality of life (QoL) and toxicity.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Neoadjuvant capecitabine and metformin | Experimental | Drug: Capecitabine, Drug: Metformin, Radiation: Radiotherapy* Capecitabine 825 mg/m2 bid D1-5, q7d, for five weeks; * Metformin 2500mg/d for five weeks; * 3D radiotherapy 50,4Gy divided in 25 fractions |
| Neoadjuvant capecitabine and placebo | Placebo comparator | Drug: Capecitabine, Radiation: Radiotherapy, Drug: Placebo* Capecitabine 825 mg/m2 bid D1-5, q7d, for five weeks; * Placebo 2500mg/d for five weeks; * 3D radiotherapy 50,4Gy divided in 25 fractions |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 18 years or older;
- biopsy proven poorly differentiated carcinoma or adenocarcinoma of the rectum;
- lesions located within 12 cm of the anal verge (from colonoscopy assessment);
- ability to tolerate oral treatment;
- locally advanced tumor, classified by the presence of positive regional lymph nodes or primary tumor invasion beyond the serosa (T3 or T4), assessed by MRI;
Key exclusion criteria (11 listed)
- known hypersensitivity to metformin or its excipients;
- squamous carcinomas of the rectum or anal canal;
- chronic treatment with corticosteroids or other immunosuppressive agents;
- treatment with oral antidiabetic products;
- distant metastasis at diagnosis or tumor invasion of pelvic bone structures that may proscribe curative intent surgery;
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 |
|---|---|---|
| CapecitabineAlso: XelodaCapecitabine 825mg/m2 bid, D1-D5 q7d | Drug | Neoadjuvant capecitabine and metformin, Neoadjuvant capecitabine and placebo |
| MetforminAlso: Glifage, Dimefor, Glucoformin, GlucophageMetformin up to 2500mg/d | Drug | Neoadjuvant capecitabine and metformin |
| RadiotherapyAlso: RDT3D radiotherapy 50,4Gy divided in 25 fractions | Radiation | Neoadjuvant capecitabine and metformin, Neoadjuvant capecitabine and placebo |
| PlaceboPlacebo up to 2500mg/d | Drug | Neoadjuvant capecitabine and placebo |
Primary outcome
Pathological Complete Response
Time frame: 8 to 16 weeks after neoadjuvant treatment completion
Pathological evaluation of the surgical specimen. Complete response will be defined as absence of neoplastic tissue upon pathological exam.
8 secondary outcomes
Overall Response Rate
Time frame: 4 to 6 weeks after neoadjuvant treatment completion
Sphincter Preservation Rate
Time frame: 8 to 16 weeks after neoadjuvant treatment completion
Toxicity will be assessed using National Cancer Institute Common Toxicity Criteria for Adverse Effects (NCI CTCAE) v4.03
Time frame: up to 4 weeks after neoadjuvant treatment completion
Local Recurrence Rate
Time frame: up to 5 years
Local Recurrence Free Survival
Time frame: up to 5 years
Disease Free Survival
Time frame: up to 5 years
Overall Survival
Time frame: up to 5 years
Quality of Life
Time frame: up to 20 weeks after neoadjuvant treatment completion
Results and safety
The study was stopped early (reason given: Slow Accrual). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Nov 2017.
- Individual participant dataSharing planned: No
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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.
Ligia T Macedo, MD principal investigator
Clinical Oncology Department, State University of Campinas (UNICAMP)
Jose BC Carvalheira, MD, PhD study chair
Clinical Oncology Department, State University of Campinas (UNICAMP)
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 Capecitabine, Metformin and Radiotherapy in people with Rectal Neoplasms and Adenocarcinoma, run by University of Campinas, Brazil at 1 site in Brazil.
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 8 inclusion and 11 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: stopped early, as of the sponsor's last update on 28 Nov 2017. 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 Brazil. 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. Some participants in this study may receive a placebo. 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 was stopped early (reason given: Slow Accrual). Results are not available in the source record.
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?
Pathological Complete Response (time frame: 8 to 16 weeks after neoadjuvant treatment completion). 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 28 Nov 2017.