Functional Outcome of Organ Preservation After Neo-adjuvant Chemo Radiation for Rectal Cancer

Rectal Neoplasms Clinical Trial

Official title:

Follow up and Functional Outcome of Organ Saving Treatment in Patients With Good Response to Neo-adjuvant (Chemo)Radiation for Rectal Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02278653
• Other study ID #: NL49171.068.14
• Status: Active, not recruiting
• Start date: March 2014
• Est. completion date: September 2022

Study information

• Verified date: September 2019
• Source: Maastricht University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

The primary objective is to describe the functional outcome of patients that choose for organ saving treatment.

Description:

Rectal cancer is a common form of cancer. Standard treatment for locally advanced rectal cancer is a long course of neoadjuvant radiation combined with chemotherapy (CRT) followed by resection. However, neoadjuvant CRT induces downsizing and downstaging, resulting in a complete response in 15-20% of the patients. In these patients surgery may be omitted. In the investigators previous study the investigators obtained good results with an organ saving treatment. Although the mortality and morbidity associated with radical surgery is avoided, the irradiated rectum remains in situ, possibly causing functional problems.

The primary objective is to describe the functional outcome of patients that choose for organ saving treatment. Functional outcome will be evaluated with questionnaires (quality of life) and manometric measurements (maximal resting pressure, maximal squeezing pressure, sphincter length, percentage asymmetry of the resting sphincter, sustained duration, length of the high pressure zone, rectoanal inhibitory reflex, rectal sensory threshold, and rectal compliance).

Secondary objectives include: the estimation of the cumulative risk of local failure within 5 years, the estimation of the cumulative risk of disease-free, distant-metastasis-free and overall survival within 5 years, determine the percentage of patients that chooses organ saving treatment instead of standard resection, determine the compliance to intensive follow-up, and compare the cost-effectiveness of organ saving treatment to standard surgical resection over a period of 5 years. These objectives will be assessed by frequent revision of the electronic patient file, as the patient is followed up to four times per year.

Study design: prospective observational registration study with 'invasive diagnostic procedures' Study population: The population will consist of patients, aged 18 years or older, with locally advanced rectal cancer who after chemoradiation have a clinical complete response (ycT0N0) or very good response (ycT1-2N0).

Main study parameters/endpoints: The main study endpoint is the functional outcome scores based on questionnaires and manometric measurements Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The questionnaires take approximately 20 minutes to complete. There is a relatively low rate of side effects associated with manometric measurements. Results of this study will contribute to better understanding of functional complaints after rectal cancer treatment.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 100
• Est. completion date: September 2022
• Est. primary completion date: October 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 18 years old

• Patients with primary rectal cancer without distant metastases who underwent CRT and show clinical complete response or very good response :

• Clinical complete response (ycT0N0) after neo-adjuvant chemoradiation will be determined clinically (digital rectal examination, endoscopy) and radiologically (contrast-enhanced-MRI)

• Very good response (ycT1-2N0) after neo-adjuvant chemoradiation will be determined clinically (digital rectal examination, endoscopy) and radiologically (contrast-enhanced-MRI). These patients will undergo a TEM to resect the small residual tumor

• Comprehension of the alternative strategies and the concept of unknown risks are clear to the patient

• Choosing for the organ-saving treatment option (wait&see policy or TEM)

• Informed consent

Exclusion Criteria:

• Unable to understand or read Dutch

• Unwilling to comply to the questionnaires or manometric measurement.

Related Conditions & MeSH terms

• Rectal Neoplasms

Intervention

Other:
• Questionnaires for the evaluation of Quality of Life
European Organisation for Research and Treatment of Cancer (EORTC) QLQ-30 questionnaire, version 3.0, Global Quality of Life Score Short Form (36) health survey EORTC CR38 Vaizey score Low Anterior Resection Syndrome (LARS) score International Index of Erectile Function for men International Prostate Symptom Score for men Female Sexual Function Index for women
• Manometry
Manometry is a tool to measure the anal sphincter function. Patients do not need any bowel preparation before this procedure. During the examination a catheter tip will be positioned in the rectum above the sphincter and a small balloon will be inflated. This balloon is connected to a device that registers the measurements. Patients will receive instructions; e.g. squeeze, push, and cough. The procedure takes approximately 10 minutes and is not experienced as painful. Several parameters will be measured: the mean basal pressure, the maximum squeeze pressure, first sensation, first urge to defecate and the maximum tolerable volume. The manometric measurement will take place on the same day as the endoscopy and MRI (standard follow-up).

Locations

Country	Name	City	State
Netherlands	MUMC+	Maastricht

Sponsors (2)

Lead Sponsor	Collaborator
Maastricht University Medical Center	Dutch Cancer Society

Country where clinical trial is conducted

Netherlands, 

References & Publications (8)

Curvo-Semedo L, Lambregts DM, Maas M, Thywissen T, Mehsen RT, Lammering G, Beets GL, Caseiro-Alves F, Beets-Tan RG. Rectal cancer: assessment of complete response to preoperative combined radiation therapy with chemotherapy--conventional MR volumetry versus diffusion-weighted MR imaging. Radiology. 2011 Sep;260(3):734-43. doi: 10.1148/radiol.11102467. Epub 2011 Jun 14. — View Citation

Habr-Gama A, Perez RO, Proscurshim I, Campos FG, Nadalin W, Kiss D, Gama-Rodrigues J. Patterns of failure and survival for nonoperative treatment of stage c0 distal rectal cancer following neoadjuvant chemoradiation therapy. J Gastrointest Surg. 2006 Dec;10(10):1319-28; discussion 1328-9. — View Citation

Habr-Gama A, Perez RO, Wynn G, Marks J, Kessler H, Gama-Rodrigues J. Complete clinical response after neoadjuvant chemoradiation therapy for distal rectal cancer: characterization of clinical and endoscopic findings for standardization. Dis Colon Rectum. 2010 Dec;53(12):1692-8. doi: 10.1007/DCR.0b013e3181f42b89. — View Citation

Lambregts DM, Beets GL, Maas M, Kessels AG, Bakers FC, Cappendijk VC, Engelen SM, Lahaye MJ, de Bruïne AP, Lammering G, Leiner T, Verwoerd JL, Wildberger JE, Beets-Tan RG. Accuracy of gadofosveset-enhanced MRI for nodal staging and restaging in rectal cancer. Ann Surg. 2011 Mar;253(3):539-45. doi: 10.1097/SLA.0b013e31820b01f1. — View Citation

Lambregts DM, Maas M, Bakers FC, Cappendijk VC, Lammering G, Beets GL, Beets-Tan RG. Long-term follow-up features on rectal MRI during a wait-and-see approach after a clinical complete response in patients with rectal cancer treated with chemoradiotherapy. Dis Colon Rectum. 2011 Dec;54(12):1521-8. doi: 10.1097/DCR.0b013e318232da89. — View Citation

Lambregts DM, Vandecaveye V, Barbaro B, Bakers FC, Lambrecht M, Maas M, Haustermans K, Valentini V, Beets GL, Beets-Tan RG. Diffusion-weighted MRI for selection of complete responders after chemoradiation for locally advanced rectal cancer: a multicenter study. Ann Surg Oncol. 2011 Aug;18(8):2224-31. doi: 10.1245/s10434-011-1607-5. Epub 2011 Feb 23. — View Citation

Maas M, Beets-Tan RG, Lambregts DM, Lammering G, Nelemans PJ, Engelen SM, van Dam RM, Jansen RL, Sosef M, Leijtens JW, Hulsewé KW, Buijsen J, Beets GL. Wait-and-see policy for clinical complete responders after chemoradiation for rectal cancer. J Clin Oncol. 2011 Dec 10;29(35):4633-40. doi: 10.1200/JCO.2011.37.7176. Epub 2011 Nov 7. — View Citation

Maas M, Nelemans PJ, Valentini V, Das P, Rödel C, Kuo LJ, Calvo FA, García-Aguilar J, Glynne-Jones R, Haustermans K, Mohiuddin M, Pucciarelli S, Small W Jr, Suárez J, Theodoropoulos G, Biondo S, Beets-Tan RG, Beets GL. Long-term outcome in patients with a pathological complete response after chemoradiation for rectal cancer: a pooled analysis of individual patient data. Lancet Oncol. 2010 Sep;11(9):835-44. doi: 10.1016/S1470-2045(10)70172-8. Epub 2010 Aug 6. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Functional outcome	Functional outcome scores of patients that are treated with an organ saving strategy compared to patients who undergo the standard resection as described in literature.; Functional outcome will be evaluated with the following questionnaires: European Organisation for Research and Treatment of Cancer (EORTC) QLQ-30 questionnaire, version 3.0, Global Quality of Life Score; Short Form (36) health survey; EORTC CR38; Vaizey score; Low Anterior Resection Syndrome (LARS) score; International Index of Erectile Function for men; International Prostate Symptom Score for men; Female Sexual Function Index for women; Functional outcome will be measured by manometric measurements: mean basal pressure (mmH2O); maximum squeeze pressure (mmH2O); first sensation (mL); first urge to defecate (mL); maximum tolerable volume (mL)	5 years
Secondary	Cumulative risk of local failure	All patients with a local recurrence will be excluded form further follow-up. This information will be based on an MRI of the lower abdomen in combination with endoscopy.	5 years
Secondary	Cumulative risks of disease-free, distant-metastasis free and overall survival		5 years
Secondary	The percentage of patients that choose the alternative strategies instead of traditional strategies and the motivation for their choice		3 years
Secondary	The compliance to the intensive follow-up schedule	All patients are intended to participate in the standard follow-up schedule. Some of them may drop out due to other illness, ageing or other reasons. These patients will be included in the analysis as far as they participated.	5 years
Secondary	Early detection of local failure (standard surgery still possible)	In the first year, every three months an MRI of the lower abdomen is made in combination with an endoscopy. From the second to the fifth year, these investigations will be done twice a year. With these short intervals, it is know that local recurence is detected in an early fase.	5 years