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

• ClinicalTrials.gov Identifier: NCT02314871
• Recruitment Status: Completed
• First Posted: December 11, 2014
• Last Update Posted: March 13, 2019
• Sponsor: The Institute of Molecular and Translational Medicine, Czech Republic
• Collaborators: Brno University Hospital; Tomas Bata Hospital, Czech Republic
• Information provided by (Responsible Party): Marian Hajduch, M.D., Ph.D., The Institute of Molecular and Translational Medicine, Czech Republic

Study Description

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

• 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
• Actual Primary Completion Date: March 2019
• Actual Study Completion Date: March 2019

Arms and Interventions

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

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

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• 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

Locations

Czechia

Brno University Hospital

Brno, Jihomoravsky Kraj, Czechia, 62500

T. Bata Regional Hospital Zlin

Zlin, Jihomoravsky Kraj, Czechia, 76275

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

Additional Information:

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

• Responsible Party: Marian Hajduch, M.D., Ph.D., Senior Researcher, The Institute of Molecular and Translational Medicine, Czech Republic
• ClinicalTrials.gov Identifier: NCT02314871
• Other Study ID Numbers: CAREC-1
• First Posted: December 11, 2014
• Last Update Posted: March 13, 2019
• Last Verified: March 2019

Keywords provided by Marian Hajduch, 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