Rectal Sparing Approach After Preoperative Radio and/or Chemotherapy in Patients With Rectal Cancer

NCT02710812 | Unknown

• 1 other identifier: 3554/AO/15
• Study Type: observational
• Target: 164
• Locations: 1 country
• Sites: 1

Brief Summary

The proposed study is an observational, prospective, multicenter study of patients undergoing neoadjuvant therapy for medium-low rectal cancer. Recently the investigators have published the findings of a multicenter Italian phase II study showing that the rate of local recurrence, with a 3 year follow-up, is less than 5% in patients with baseline T2-3 mid-low rectal cancer who, after preoperative chemoradiotherapy (pCRT), showed a major clinical response and underwent a transanal local excision. Based on these results, an organ-sparing approach for patients showing a major clinical response is feasible without reducing the good results obtained with the standard treatment. While a phase III trial is the best way to compare the standard treatment with the organ-sparing approach (local excision or wait-and-see) it is impracticable and likely unethical. An observational study is therefore one of the best way to evaluate the impact that an organ-sparing approach may have on oncological outcomes, quality of life, and bowel function for patients with rectal cancer who, after a pCRT, show a clinical major/complete response. This phase II trial is designed to test the hypothesis that conservative treatments, in patients with low-mid rectal cancer who undergo a major or complete clinical response after neoadjuvant treatment, will be safe and effective compared to standard surgery. The investigators will compare rectum-sparing approaches to standard surgery, firstly in terms of rate of organ preservation at 2 years. Additionally they will compare survival outcomes (DFS, OS), stoma rates, clinical and tumor factors related to pathological complete response, correlation between major and complete clinical response. To add value, the investigators will measure QoL in patients treated with rectum-sparing approaches in comparison to patients treated with standard surgery (TME or abdomino-perineal amputation). Rectum-sparing approach can be considered clinically acceptable if percentage of conservation of the rectum at two years is not less than 50%. The collected data on 164 patients who underwent "rectum-sparing" allow to test the hypothesis that the rectum is preserved in 60% of patients with 80% power (exact binomial test for proportions, alpha = 5 %, 1 tail) and the study will be considered positive if it obtains a frequency of conservation of the rectum of not less than 87 cases. The analysis results will be reported in accordance with STROBE guidelines (von Elm et al., 2008). For all analyzes, continuous variables are described using the mean and standard deviation of position and appropriate measures when appropriate. Categorical variables will be described using the contingency tables.

Conditions

Rectal Neoplasms

Outcome Measures

Primary Outcomes (1)

• Rate of organ preservation

  The primary objective of th study is to determine the rate of organ preservation at 2 years in patients with rectal cancer treated with neoadjuvant therapy followed by conservative treatment (LE and wait-and-see).

  2 years

Secondary Outcomes (12)

• Rate of overall survival (OS)

  2, 3, 5 years

• Rate of disease-free survival (DFS)

  2, 3, 5 years

• Rate of relapse-free local recurrence

  2, 3, 5 years

• Rate of patients without stoma

  2, 5 years

• Rate of pCR

  At surgery time

Study Arms (1)

Rectum sparing group

Patients who have all of the following requirements: 1. Major or complete clinical response at restaging after 7-8 weeks from the end of neoadjuvant therapy, confirmed at second restaging (after 11-12 weeks from the end of neoadjuvant therapy); 2. Written informed consent (after 2nd restaging). Note: They will be subject to wait-and-see approach only patients with cCR.

Procedure: Local Excision or Wait-and-See

Interventions

Local Excision or Wait-and-See PROCEDURE

Local excision can be done both with traditional technique and with endoscopic technique (TEM, TAMIS, etc.). The following principles should be respected: 1. A gross margin of at least 0.5 cm; 2. full-thickness excision including mucosa, submucosa, muscle and peri-rectal fat; 3. determination of the specimen on the support by pins at the edges in order to facilitate the interpretation of histological pathologist.

Rectum sparing group

Eligibility Criteria

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

Study Population

All patients underwent neoadjuvant therapy for rectal cancer and have a major or complete clinical response. Definitions: Major clinical response (mCR) is defined as the absence of: • palpable mass at digital rectal exploration, pathological lymph nodes (\> 5 mm in diameter along short axis) to pelvic MRI, deep or shallow ulcers \> 2 cm in diameter at rectoscopy; Clinical complete response (cCR) is defined as the absence of: • palpable mass at digital rectal exploration, pathological lymph nodes (\> 5 mm in diameter along the short axis) to the pelvic MRI, any endoscopic lesion (a flat scar is considered as absence of endoscopic lesions).

You may qualify if:

• Patients with mCR or cCR at restaging performed after 11-12 weeks after the end of radiotherapy;
• Ability to understand the protocol;
• Acquisition of written informed consent.

You may not qualify if:

• The LE local will be considered as proper treatment if histological assessment will document:
• ypT0 (cCR);
• ypT1 but with a TRG degree \< 3 and with a differentiation degree of G1-2;
• histologically margins not involved.
• LE will be considered as excessive handling and patients will be advised to undergo TME if histological assessment will document the presence of cancer with at least one of the following characteristics:
• ypT ≥ 2;
• Positive margins;
• TRG ≥ 3;
• Poor differentiation degree (G3).
• Indications to wait-and-see approach This approach, that consists only in observation after neoadjuvant therapy, is reserved only to those patients who show cCR at restaging, as defined previously.

Sponsors & Collaborators

• University of Padova: lead
• Istituto Oncologico Veneto IRCCS: collaborator
• Centro di Riferimento Oncologico - Aviano: collaborator
• Istituto Nazionale per lo Studio e la Cura dei Tumori: collaborator
• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: collaborator
• Azienda Ospedaliero, Universitaria Ospedali Riuniti: collaborator

Study Sites (1)

Clinica Chirurgica I - Dipartimento di Scienze Chirurgiche, Oncologiche e Gastroenterologiche. Azienda Ospedaliera - Università di Padova

Padua, Italy, 35128, Italy

RECRUITING

Related Publications (1)

• Barina A, De Paoli A, Delrio P, Guerrieri M, Muratore A, Bianco F, Vespa D, Asteria C, Morpurgo E, Restivo A, Coco C, Pace U, Belluco C, Aschele C, Lonardi S, Valentini V, Mantello G, Maretto I, Del Bianco P, Perin A, Pucciarelli S. Rectal sparing approach after preoperative radio- and/or chemotherapy (RESARCH) in patients with rectal cancer: a multicentre observational study. Tech Coloproctol. 2017 Aug;21(8):633-640. doi: 10.1007/s10151-017-1665-1. Epub 2017 Jul 28.

  PMID: 28755256 DERIVED

MeSH Terms

Conditions

Rectal Neoplasms

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

Study Officials

• Salvatore Pucciarelli, MD

  University of Padova

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Salvatore Pucciarelli, MD

CONTACT

39 0498212208; puc@unipd.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: March 4, 2016
• First Posted: March 17, 2016
• Study Start: January 1, 2016
• Primary Completion: January 1, 2021
• Study Completion: August 1, 2021
• Last Updated: March 21, 2016

Record last verified: 2016-03

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)