Effects of Different Types of Perioperative Analgesia on Minimal Residual Disease Development After Colon Cancer Surgery

Study Description

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Brief Summary:

The aim of this study is to compare the effects of three types of perioperative analgesia on the number of circulating cancer cells (representing minimal residual disease) following radical colon cancer surgery. Patients will be randomized into one of three groups. The intervention group will receive combined regional and general anesthesia during surgery and postoperative epidural analgesia. The two control groups will receive balanced general anesthesia and either morphine-based or piritramide-based postoperative analgesia. We hypothesize that epidural analgesia will be favorable to both piritramide-based and morphine-based analgesia and that piritramide-based analgesia will be favorable to morphine-based analgesia with regard to the number of circulating cancer cells and its development in the early postoperative period.

Condition or disease	Intervention/treatment	Phase
Colon Cancer; Minimal Residual Disease	Other: Epidural analgesia; Drug: Piritramide; Drug: Morphine	Phase 4

Detailed Description:

Techniques of regional analgesia such as epidural analgesia may favorably influence metastasis development following cancer surgery compared to analgesia based on strong opioids such as morphine or piritramide. These beneficial effects, if present, are probably attributable to less immunosuppression of antimetastatic immune defenses.

The aim of this study is to identify techniques of perioperative analgesia with the potential to prevent metastasis development in patients undergoing open radical colon cancer surgery. In the early postoperative period, a relationship between metastasis development and the number of circulating cancer cells representing minimal residual disease has been shown. Therefore, effects of epidural, morphine-based and piritramide-based analgesia on the number of circulating cancer cells will be compared at several time points during the peroperative and early postoperative periods. The number of circulating cancer cells will be assessed in peripheral venous blood samples using real-time polymerase chain reaction. Perioperative care will be standardized and patients will be followed by clinical observation, laboratory analyses and monitoring instrumentation daily during their hospital stay.

Study Design

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	60 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Effects of Different Types of Perioperative Analgesia on Minimal Residual Disease Development After Colon Cancer Surgery
Study Start Date :	January 2015
Estimated Primary Completion Date :	May 2018
Estimated Study Completion Date :	September 2018

Arms and Interventions

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm	Intervention/treatment
Active Comparator: Epidural; Patients will receive perioperative epidural analgesia. Drugs: bupivacaine 1.25 mg/ml and sufentanil 0.5 mcg/ml Form and frequency: continuous infusion Dosage: 4 - 14 ml/h with boluses 2 - 4 ml based on pain assessment Duration: as long as required	Other: Epidural analgesia; see Arm/group description; Other Name: Perioperative epidural analgesia
Active Comparator: Piritramide; Patients will receive postoperative analgesia with piritramide. Drugs: piritramide 1.0 mg/ml Form and frequency: continuous infusion Dosage: 0 - 4 ml/h with boluses 2 - 4 ml based on pain assessment Duration: as long as required	Drug: Piritramide; see Arm/group description; Other Name: Postoperative piritramide analgesia
Active Comparator: Morphine; Patients will receive postoperative analgesia with morphine. Drugs: morphine 1.0 mg/ml Form and frequency: continuous infusion Dosage: 0 - 4 ml/h with boluses 2 - 4 ml based on pain assessment Duration: as long as required	Drug: Morphine; see Arm/group description; Other Name: Postoperative morphine analgesia

Outcome Measures

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :

1. Change from baseline number of circulating cancer cells at 3 weeks after surgery [ Time Frame: Baseline prior to surgery, on day 2 postoperatively and three weeks after surgery ]
   Number of circulating cancer cells will be measured in venous blood samples. The quantitative real-time polymerase chain reaction using carcinoembryonic antigen and cytokeratine 20 as markers for circulating cancer cells will be used for minimal residual disease detection.

Secondary Outcome Measures :

1. Pain intensity assessment [ Time Frame: 3 days postoperatively ]
   Self reported pain intensity. Scale: 0 = no pain, 10 = worst pain imaginable. A score 0-10 will be recorded every four hours.

Eligibility Criteria

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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

Criteria

Inclusion Criteria:

• Patients undergoing open radical surgery for colon cancer (without known extension beyond colon)
• Age over 18 years
• Written informed consent

Exclusion Criteria:

• Allergy or intolerance of morphine, piritramide, marcaine, sufentanil or volatile anesthetics
• History of colon cancer resection
• Other cancer present (apart from those in complete long-term remission for minimum 6 months)
• Chronic opioid medication and/or opioid administration 7 days or less prior to surgery
• Any contraindication to thoracic epidural anesthesia/analgesia
• Systemic therapy with immunosuppressive drugs or corticoids (apart from topical and inhalational)
• Any surgery within the last 30 days (apart from minor day-case procedures)  - Chronic or acute infectious disease, particularly hepatitis, AIDS, tuberculosis

Contacts and Locations

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Contacts

Contact: Emil Berta, MD PhD	00420608801303	e.berta@email.cz
Contact: Josef Srovnal, MD PhD	00420585632111	srovnalj@upol.cz

Locations

Czech Republic
Brno University Hospital	Recruiting
Brno, Jihomoravsky kraj, Czech Republic, 62500
Contact: Petr Stourac, MD, PhD +420532233850 stouracp@fnbrno.cz
T. Bata Regional Hospital Zlin	Recruiting
Zlin, Jihomoravsky kraj, Czech Republic, 76275
Contact: Tomas Gabrhelik, MD, PhD +420577552280 Tomas.Gabrhelik@bnzlin.cz

Sponsors and Collaborators

The Institute of Molecular and Translational Medicine, Czech Republic

Brno University Hospital

Tomas Bata Hospital, Czech Republic

Investigators

Principal Investigator:	Emil Berta, MD PhD	The Institute of Molecular and Translational Medicine

More Information

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

The Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry Palacky University Olomouc 

Responsible Party:	Emil Berta, M.D., Ph.D., Senior Researcher, The Institute of Molecular and Translational Medicine, Czech Republic
ClinicalTrials.gov Identifier:	NCT02314871 History of Changes
Other Study ID Numbers:	CAREC-1
First Posted:	December 11, 2014
Last Update Posted:	February 23, 2017
Last Verified:	February 2017

Keywords provided by Emil Berta, M.D., Ph.D., The Institute of Molecular and Translational Medicine, Czech Republic:

perioperative analgesia; minimal residual disease; cancer recurrence; epidural; morphine	piritramide; colon; cancer; circulating cancer cells; colon cancer surgery

Additional relevant MeSH terms:

Pirinitramide; Colonic Neoplasms; Neoplasm, Residual; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases	Intestinal Diseases; Neoplastic Processes; Pathologic Processes; Morphine; Analgesics, Opioid; Narcotics; Central Nervous System Depressants; Physiological Effects of Drugs; Analgesics; Sensory System Agents; Peripheral Nervous System Agents