Clinical trial NCT02473094: Neoadjuvant Metformin in Association to Chemoradiotherapy for Locally Advanced Rectal Cancer
Official title: Metformin in Association to Chemoradiotherapy for the Neoadjuvant Treatment of Locally Advanced Rectal Cancer: a Randomized, Placebo-controlled Phase II Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Rectal Neoplasms
Adenocarcinoma
Carcinoma
Keywords: Metformin
Rectal Cancer
Rectum
Radiotherapy
Capecitabine
Neoadjuvant
Adenocarcinoma
Carcinoma
Lead sponsor: University of Campinas, Brazil
Sponsor class: OTHER
First posted: 2015-06-16
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: Inclusion Criteria:

* 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);

Exclusion Criteria:

* 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;
* 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.

Primary outcomes:
measure: Pathological Complete Response
timeFrame: 8 to 16 weeks after neoadjuvant treatment completion
Secondary outcomes:
measure: Overall Response Rate
timeFrame: 4 to 6 weeks after neoadjuvant treatment completion
measure: Sphincter Preservation Rate
timeFrame: 8 to 16 weeks after neoadjuvant treatment completion
measure: Toxicity will be assessed using National Cancer Institute Common Toxicity Criteria for Adverse Effects (NCI CTCAE) v4.03
timeFrame: up to 4 weeks after neoadjuvant treatment completion
measure: Local Recurrence Rate
timeFrame: up to 5 years
measure: Local Recurrence Free Survival
timeFrame: up to 5 years
measure: Disease Free Survival
timeFrame: up to 5 years
measure: Overall Survival
timeFrame: up to 5 years
measure: Quality of Life
timeFrame: up to 20 weeks after neoadjuvant treatment completion
Other outcomes:
Locations:
city: Campinas
country: Brazil
facility: Clinical Oncology Department - General Hospital - State University of Campinas (UNICAMP)
state: São Paulo
Study officials:
affiliation: Clinical Oncology Department, State University of Campinas (UNICAMP)
name: Ligia T Macedo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Clinical Oncology Department, State University of Campinas (UNICAMP)
name: Jose BC Carvalheira, MD, PhD
role: STUDY_CHAIR
References: