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

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ClinicalTrials.gov Identifier: NCT02710812
Recruitment Status : Recruiting
First Posted : March 17, 2016
Last Update Posted : March 21, 2016
Sponsor:
Collaborators:
Istituto Oncologico Veneto IRCCS
Centro di Riferimento Oncologico - Aviano
Istituto Nazionale per lo Studio e la Cura dei Tumori
Policlinico Universitario Agostino Gemelli
Azienda Ospedaliero, Universitaria Ospedali Riuniti
Information provided by (Responsible Party):
Pucciarelli Salvatore, University of Padova

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.


Condition or disease Intervention/treatment
Rectal Neoplasms Procedure: Local Excision or Wait-and-See

  Show Detailed Description

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Study Type : Observational
Estimated Enrollment : 164 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Rectal Sparing Approach After Preoperative Radio and/or Chemotherapy in Patients With Rectal Cancer
Study Start Date : January 2016
Estimated Primary Completion Date : January 2021
Estimated Study Completion Date : August 2021

Group/Cohort Intervention/treatment
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

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.




Primary Outcome Measures :
  1. Rate of organ preservation [ Time Frame: 2 years ]
    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).


Secondary Outcome Measures :
  1. Rate of overall survival (OS) [ Time Frame: 2, 3, 5 years ]
    Rate of overall survival (OS) at 2, 3, and 5 years after initiation of treatment

  2. Rate of disease-free survival (DFS) [ Time Frame: 2, 3, 5 years ]
    Rate of disease-free survival (DFS) at 2, 3, and 5 years after initiation of treatment

  3. Rate of relapse-free local recurrence [ Time Frame: 2, 3, 5 years ]
    Rate of relapse-free local recurrence at 2, 3, and 5 years after initiation of treatment

  4. Rate of patients without stoma [ Time Frame: 2, 5 years ]
    Rate of patients without stoma at 2 and at 5 years

  5. Rate of pCR [ Time Frame: At surgery time ]
    Rate of pCR in patients who are treated with LE and with conventional surgery (TME);

  6. Morbidity [ Time Frame: 30 days after surgery ]
    Morbidity after neoadjuvant therapy and conservative approach or TME

  7. Mortality [ Time Frame: 30 days after surgery ]
    Mortality after neoadjuvant therapy and conservative approach or TME

  8. Rate of patients undergoing conservative treatment [ Time Frame: 5 years ]
    Rate of patients undergoing conservative treatment on total patients running pRT and/or CT

  9. Memorial Sloan-Kettering Cancer Center Bowel Function Instrument [ Time Frame: T0: before neoadjuvant treatment; T1: at 10-12 weeks after neoadjuvant treatment; T2: 6 months after T1; T3: 12 months after T1 ]
    MSKCC Bowel Function Instrument (Temple et al., 2005). The questionnaire consists of 18 items that include three subscales (frequency, dietary and urgency/soiling), four individual items of clinical significance ranging (incomplete emptying after a bowel movement, a second bowel movement within 15 min, knowing the difference between gas and bowel movement, inability to control the passage of flatus), and one total score obtained by the sum for all 18 items. Responses to individual items are given on a 5-point Likert scale with the first item (daily frequency of bowel movements) response divided into quintiles. Higher scores indicate better bowel function. The questionnaire has been translated and validated for Italian-speaking patients (Zotti et al., 2011).

  10. Fecal Incontinence Quality of Life Scale [ Time Frame: T0: before neoadjuvant treatment; T1: at 10-12 weeks after neoadjuvant treatment; T2: 6 months after T1; T3: 12 months after T1 ]
    FIQL (Rockwood et al., 2000). The questionnaire measures specific quality of life issues expected to affect patients with faecal incontinence. This instrument is composed of 29 items within four domains: lifestyle issues, coping/behaviour, depression/self-perception and embarrassment. The scores range from a minimum score of 1 to a maximum of 4, for all of the scales. The Italian version of the questionnaire has been validated by Altomare et al. (2004).

  11. European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 [ Time Frame: T0: before neoadjuvant treatment; T1: at 10-12 weeks after neoadjuvant treatment; T2: 6 months after T1; T3: 12 months after T1 ]
    EORTC QLQ-C30 (Aaronson et al., 1993). The questionnaire assesses health status and quality of life of cancer patients using 30 items grouped in one global scale, five multi-item functioning scales (physical, role, social, emotional, and cognitive functions), three symptom scales (fatigue, nausea/vomiting and pain) and six single symptom items (dyspnoea, insomnia, appetite loss, constipation, diarrhoea and financial impact). The items are scored on a four-point Likert scale with higher scores indicating a better level of functioning or a higher level of symptoms. The validity and reliability of the Italian versions of the questionnaire have been established (Apolone et al., 1998).

  12. European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Colorectal Cancer Module 29 [ Time Frame: T0: before neoadjuvant treatment; T1: at 10-12 weeks after neoadjuvant treatment; T2: 6 months after T1; T3: 12 months after T1 ]
    EORTC QLQ-CR29 (Whistance et al., 2009). The questionnaire measures health-related quality of life in patients with colorectal cancer, using 29 items grouped in four functional scale (body image, anxiety, weight, sex interest men/woman) and 18 symptom scale (urinary frequency, blood and mucus in stool, stool frequency, urinary incontinence, dysuria, abdominal pain, buttock pain, bloating, dry mouth, hair loss, taste, flatulence, fecal incontinence, sore skin, embarrassment, stoma care problems, impotence, dyspareunia). The items are scored on a four-point Likert scale with higher scores indicating a better level of functioning or a higher level of symptoms. The Italian version of the questionnaire is validated and widely used (Whistance et al.,2009).



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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).

Criteria

All patients underwent neoadjuvant therapy for rectal cancer will be registered provided that they satisfy the following requirements:

  1. histologically documented adenocarcinoma of the rectum;
  2. Up to 12 cm from the anal verge to rectoscopy;
  3. Minimum age 18 years old;
  4. Able to undergo both neoadjuvant treatment, TME than conservative treatment;
  5. For which RT and/or CT fluoropyrimidine ± oxaliplatin or biologic drugs regimens are expected;
  6. Able to understand risks and benefits of the protocol.

Criteria for inclusion in the rectum-sparing group (study group):

Of patients registered, they will be eligible for the study rectum-sparing those 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.

Criteria of esclusion from protocol:

At restaging after 7-8 weeks and/or after 11-12 weeks, patients who show one of the following characteristics:

  1. palpable mass on digital rectal examination;
  2. deep ulcer with surface > 2 cm in diameter or obvious signs of endoscopic residual disease;
  3. presence of metastatic lymph nodes at MRI (> 5 mm along short axis).

Inclusion criteria to be included to EL or wait- and-see approach:

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

Inclusion and exclusion criteria to be observed (just follow-up) after LE:

The LE local will be considered as proper treatment if histological assessment will document:

  1. ypT0 (cCR);
  2. ypT1 but with a TRG degree < 3 and with a differentiation degree of G1-2;
  3. 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:

  1. ypT ≥ 2;
  2. Positive margins;
  3. TRG ≥ 3;
  4. 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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02710812


Contacts
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Contact: Salvatore Pucciarelli, MD 39 0498212208 puc@unipd.it

Locations
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Italy
Clinica Chirurgica I - Dipartimento di Scienze Chirurgiche, Oncologiche e Gastroenterologiche. Azienda Ospedaliera - Università di Padova Recruiting
Padova, Italy, 35128
Contact: Salvatore Pucciarelli, MD    +39 0498212208    puc@unipd.it   
Contact: Mariasole Bigon    +39 0498211237    mariasole.bigon@gmail.com   
Principal Investigator: Salvatore Pucciarelli, MD         
Sub-Investigator: Isacco Maretto, MD         
Sponsors and Collaborators
University of Padova
Istituto Oncologico Veneto IRCCS
Centro di Riferimento Oncologico - Aviano
Istituto Nazionale per lo Studio e la Cura dei Tumori
Policlinico Universitario Agostino Gemelli
Azienda Ospedaliero, Universitaria Ospedali Riuniti
Investigators
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Principal Investigator: Salvatore Pucciarelli, MD University of Padova

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Pucciarelli Salvatore, Associate Professor, University of Padova
ClinicalTrials.gov Identifier: NCT02710812     History of Changes
Other Study ID Numbers: 3554/AO/15
First Posted: March 17, 2016    Key Record Dates
Last Update Posted: March 21, 2016
Last Verified: March 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
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Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases