Neoadjuvant Metformin in Association to Chemoradiotherapy for Locally Advanced Rectal Cancer

NCT02473094 | Terminated Phase 2 DMC

• 1 other identifier: NEOMETRE201501
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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.

Conditions

Rectal Neoplasms; Adenocarcinoma; Carcinoma

Keywords

Metformin; Rectal Cancer; Rectum; Radiotherapy; Capecitabine; Neoadjuvant; Adenocarcinoma; Carcinoma

Outcome Measures

Primary Outcomes (1)

• Pathological Complete Response

  Pathological evaluation of the surgical specimen. Complete response will be defined as absence of neoplastic tissue upon pathological exam.

  8 to 16 weeks after neoadjuvant treatment completion

Secondary Outcomes (8)

• Overall Response Rate

  4 to 6 weeks after neoadjuvant treatment completion

• Sphincter Preservation Rate

  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

  up to 4 weeks after neoadjuvant treatment completion

• Local Recurrence Rate

  up to 5 years

• Local Recurrence Free Survival

  up to 5 years

Study Arms (2)

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

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

Drug: Capecitabine; Radiation: Radiotherapy; Drug: Placebo

Interventions

Capecitabine DRUG

Capecitabine 825mg/m2 bid, D1-D5 q7d

Also known as: Xeloda

Neoadjuvant capecitabine and metformin; Neoadjuvant capecitabine and placebo

Metformin DRUG

Metformin up to 2500mg/d

Also known as: Glifage, Dimefor, Glucoformin, Glucophage

Neoadjuvant capecitabine and metformin

Radiotherapy RADIATION

3D radiotherapy 50,4Gy divided in 25 fractions

Also known as: RDT

Neoadjuvant capecitabine and metformin; Neoadjuvant capecitabine and placebo

Placebo DRUG

Placebo up to 2500mg/d

Neoadjuvant capecitabine and placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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);

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Campinas, Brazil: lead

Study Sites (1)

Clinical Oncology Department - General Hospital - State University of Campinas (UNICAMP)

Campinas, São Paulo, 13083888, Brazil

Location

MeSH Terms

Conditions

Rectal Neoplasms; Adenocarcinoma; Carcinoma

Interventions

Capecitabine; Metformin; Radiotherapy

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Biguanides; Guanidines; Amidines; Organic Chemicals; Therapeutics

Study Officials

• Ligia T Macedo, MD

  Clinical Oncology Department, State University of Campinas (UNICAMP)

  PRINCIPAL INVESTIGATOR

• Jose BC Carvalheira, MD, PhD

  Clinical Oncology Department, State University of Campinas (UNICAMP)

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Oncology

Study Record Dates

• First Submitted: June 13, 2015
• First Posted: June 16, 2015
• Study Start: July 1, 2015
• Primary Completion: February 1, 2016
• Study Completion: February 1, 2016
• Last Updated: November 28, 2017

Record last verified: 2017-11

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)