Cd133+ Cell Infusion in Patients With Colorectal Liver Metastases. (cellcol)

Cd133+ Cell Infusion in Patients With Colorectal Liver Metastases That Are Going to be Submitted to a Major Liver Resection

Treatment of patients with metastatic colorectal carcinoma is surgical resection. Only 10-15% of the patients will be candidates for curative resection. After response to chemotherapy this figure rises 10-13% more. To perform the surgery it is necessary to have a sufficient remnant liver volume (RLV), which allows maintaining optimal liver function after resection. If the estimated RLV is insufficient preoperatively, portal venous embolization site (PVE) is performed for compensatory hypertrophy, thus increasing the number of resections 19%. Still, in 20% of these patients surgery can not be performed because RLV is not achieved or because the disease progresses while waiting for growth. Therefore, it is necessary to improve liver regeneration without promoting tumor growth. Studies on liver regeneration, have determined that cells (CD133 +) are involved in the liver hypertrophy that occurs after hepatectomy. CD133 + have been used to induce liver hypertrophy with encouraging results. This population of CD133 +, can be selected from peripheral blood after stimulation with Granulocyte colony-stimulating factor (G-CSF), being able to obtain a large number of them. The investigators propose to treat patients who do not meet criteria for surgery because of insufficient volume <40%, with CD133 + and portal embolization in order to carry out a surgical resection in a second place.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: CD133+ infusion; Other: portal vein embolization

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 2

Contacts and Locations

Study Locations

• Spain
  • Madrid, Spain, 28031
    • Hospital Clínico San Carlos
  • Madrid, Spain, 28040
    • Alejandra Garcia Botella

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

1. Men and women between ≥ 18 years and ≤ 80. Women in fertile age should use contraceptive methods recommended by the Clinical Trial Facilitation Group (CTFG).
2. ECOG (Eastern Cooperative Oncology Group) quality of life scale ≤ 2.

3. Patients with hepatic metastases of colorectal carcinoma and insufficient hepatic remnant function to perform a major hepatectomy. This volume would be calculated by Positron emission tomography-Computed tomography (PET-CT) images or 64-channel multidetector CT.

   In patients who have received preoperative chemotherapy, the estimate residual liver volume to be included in the study will be <40%.

   Patients who have preserved liver function (Child ≤ B7 and International Normalized Ratio (INR) ≤ 2 in non-anticoagulated patients) and those who have not received chemotherapy, needs < 30% of residual volume to be included in the study.

4. Patients should have signed informed consent.

Exclusion criteria:

1. Pregnancy or lactation period.
2. Any condition that the investigators consider an unjustifiable risk in the patient.
3. Severe comorbidities: American Society of Anesthesiologists (ASA) ≥ 4.
4. Alterations in the hemogram and morphological alterations, evaluated by hematologist prior to administration of G-CSF.
5. Liver function: Child ≥ B7 and INR ≥ 2 in non-anticoagulated patients. In anticoagulated patients the values will have to be reverse, prior to surgery.
6. Patients who have not received research drugs in the last 30 days or in the period of 5 elimination half-life.
7. In patients on chemotherapy treatment, G-CSF can not be administered until 48 hours after the last administration of chemotherapy. Patients who have received Bevacizumab must wait 30 days since the last administration.
8. In addition, all those aspects that prevent the patient from being part of the study, understand the rules, follow the instructions given, or other aspects.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PVE + CD133; preop portal vein embolization + stem cells infusion	Drug: CD133+ infusion; Infusion of cells cd133+; Other: portal vein embolization; portal vein embolization
Sham Comparator: PVE; only preop portal vein embolization	Other: portal vein embolization; portal vein embolization

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Liver volume	Liver volume estimated by computed tomography	once residual liver volume reach >40%, an average of 5 weeks.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Liver volume	Liver volume estimated by computed tomography	Post-surgery follow-up visits the first 30 days
Liver volume	Liver volume estimated by computed tomography	Post-surgery follow-up visits the first 90 days
Liver volume	Liver volume estimated by computed tomography	Post-surgery follow-up visits the first 180 days
Liver volume	Liver volume estimated by computed tomography	Post-surgery follow-up visits the first 12 months
Liver volume	Liver volume estimated by computed tomography	Post-surgery follow-up visits the first 18 months
Liver volume	Liver volume estimated by computed tomography	Post-surgery follow-up visits the first 24 months

Collaborators and Investigators

• Sponsor: Hospital San Carlos, Madrid

Publications and helpful links

General Publications

• Garcia-Botella A, Saez-Carlin P, Mendez R, Martin MP, Ortega L, Mendez JV, Garcia-Paredes B, Diez-Valladares L, Torres AJ. CD133 + cell infusion in patients with colorectal liver metastases going to be submitted to a major liver resection (CELLCOL): A randomized open label clinical trial. Surg Oncol. 2020 Jun;33:224-230. doi: 10.1016/j.suronc.2019.10.005. Epub 2019 Oct 7.

Study record dates

Study Major Dates

• Study Start (Actual): May 31, 2019
• Primary Completion (Actual): December 31, 2020
• Study Completion (Actual): June 30, 2021

Study Registration Dates

• First Submitted: November 18, 2016
• First Submitted That Met QC Criteria: January 11, 2019
• First Posted (Actual): January 14, 2019

Study Record Updates

• Last Update Posted (Actual): September 27, 2021
• Last Update Submitted That Met QC Criteria: September 22, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms
• Other Study ID Numbers: 2014-001402-18

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No