Trial Title:
TINzaparin Prophylaxis in Patients With Metastatic Colorectal Cancer
NCT ID:
NCT05625932
Condition:
Colorectal Cancer Metastatic
Thromboembolism
Conditions: Official terms:
Colorectal Neoplasms
Thromboembolism
Tinzaparin
Heparin, Low-Molecular-Weight
Dalteparin
Conditions: Keywords:
LMWH
Prophylaxis
Thromboembolic event
Colorectal cancer
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
Two-arm, randomized, non-placebo controlled, open-label
Primary purpose:
Prevention
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Tinzaparin
Description:
Patients < 80 kg will receive a fixed dose of 4500 IU daily. Patients between 80-100 kg
will receive a fixed dose of 6000 IU daily. Patients > 100 kg will receive a fixed dose
of 8000 IU daily.
Arm group label:
Experimental arm
Other name:
Innohep
Summary:
Patients with metastatic colorectal cancer (mCRC) who are scheduled to receive systemic
cancer therapy have an increased risk for venous thromboembolic (VTE) events compared
with the general population.
PROTINCOL is a randomized, open label, non placebo-controlled, low intervention, and
phase III clinical trial that will recruit patients with mCRC. The study hypothesizes
that prophylaxis with Tinzaparin could prevent the appearance of symptomatic and
incidental VTE.
All patients will receive the first-line anticancer treatment deemed more appropriate
according to the physician criteria. Enrolled patients are randomized in a 1:1 ratio
(stratifying by BRAF/RAS, resection of primary tumor, and anti-angiogenic first-line
treatment) to: control arm (no interventions related to VTE risk and no placebo) or
experimental arm (prophylactic Tinzaparin at a fixed dose of 4500 IU/day in patients with
up to 80kg, 6000 IU/day for those between 80-100 kg, or 8000 IU/day for those >100kg).
Treatment is scheduled for a maximum period of 4 months. Treatment could be stopped
earlier in case of unacceptable toxicity, patient consent withdrawal, physician criteria
or end of study. Patients will undergo tumor and VTE assessments according to standard
clinical practice.
The main objective of the study is to evaluate the efficacy of tinzaparin for the
prevention of symptomatic or incidental VTE events. Secondary objectives include the
associations between VTE events and tumor characteristics (i.e. laterality, RAS/BRAF
mutations) or management (i.e. surgery or treatment with anti-angiogenic or anti-EGFR
agents), cancer-specific survival outcomes, safety, the incidence of bleeding events, and
patient-reported quality of life. The trial includes also a translational exploratory
analysis to assess the predictive value of risk assessment models and genetic risk
scores, their evolution through the study and microsatellite instability or other
biomarkers.
Detailed description:
This research study is a prospective, randomized, open label (PROBE), non
placebo-controlled, and phase III clinical trial; Investigator Initiated Study (IIS). The
study has been considered a low-interventional clinical trial.
The trial will compare the efficacy and safety of tinzaparin with a watch and wait
strategy for primary prophylaxis of symptomatic or incidental VTE in adult men and women,
18 years of age and older, with metastatic colorectal cancer who are scheduled to
initiate systemic cancer therapy as a component of their standard of care anticancer
regimen.
The study consists of 3 periods: a 4-week screening period, a 4 months treatment period
and post-treatment follow-up period until the end of treatment (EOT) visit, scheduled 2
months after the last dose of tinzaparin or 6 months from the first dose of tinzaparin
(whichever occurs latest). The duration of participation in the study for each subject is
approximately 6 months. Further long-term phone follow-up to monitor for progression and
survival could be carried out at the end of study. Tumor follow-up assessments will
adhere to the standard clinical practice within each site.
All patients will receive the first-line anticancer treatment deemed more appropriate
according to the physician criteria and current guideline recommendations. Patients in
both groups will receive supportive care as per local practice. No formal recommendations
will be issued by the study protocol regarding cancer treatment and supportive care, but
the drugs used will be recorded in the clinical report form. Constitutive use of
anticoagulant drugs will be prohibited during the treatment period.
Enrolled patients are randomized in a 1:1 ratio to the control arm, or the experimental
arm:
Control arm: A watch and wait strategy will be used. There is no placebo. Since no
reference treatment is available for long-term VTE prophylaxis in patients with cancer,
patients in the control group will not receive VTE prophylaxis outside the hospital and
will receive anticancer treatment and supportive care as per local practice. No formal
recommendations will be issued by the study protocol regarding cancer treatment and
supportive care, but the drugs used will be recorded in the clinical report form (CRF).
Patients in the control group will receive antithrombotic prophylaxis as per local
practice during hospitalizations. Any use of LMWH will be recorded in the CRF.
Experimental arm: Patients will receive prophylaxis tinzaparin at a fixed dose daily for
4 months.
The primary objective is to evaluate the efficacy of 4-months prophylaxis with tinzaparin
for the prevention of symptomatic or incidental VTE events. Secondary efficacy objectives
include the VTE incidence in specific subpopulations (stratification according to the
laterality of the primary tumor, first-line treatment with anti-EGFR or antiangiogenics,
and mutational status).
Safety of tinzaparin will be evaluated by means of relevant adverse events, incidence of
bleedings according to International Society of Thrombosis and Hemostasis (ISTH)
criteria, and patient-reported quality of life. Bleeding events will be evaluated locally
by the investigator and centrally by a blinded committee.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Male or female subjects with age ≥ 18 years.
2. Written informed consent.
3. Patients with a histologically confirmed diagnosis of stage IV colon or rectal
adenocarcinoma (mCRC).
4. Locally assessed BRAF and RAS genomic alterations available during screening.
5. Beginning of the first line of treatment for metastatic disease with chemotherapy
+/- targeted therapy (i.e. antiangiogenic, anti-EGFR, encorafenib-cetuximab doublet)
or immunotherapy.
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
7. Life expectancy >6 months.
Exclusion Criteria:
1. Contraindication to tinzaparin, or other heparins:
1. Allergy (or hypersensitivity) to heparin, tinzaparin, other LMWHs, or pork
products.
2. History or presence of heparin-induced (type II) thrombocytopenia.
3. Have or have had an epidural catheter or a traumatic spinal puncture within the
previous 7 days.
2. Prothrombin time (PT) (International normalized ratio [INR] >1.5 for any reason) or
aPTT >2 times control value.
3. Active major bleeding or conditions predisposing to major bleeding. a major bleeding
is defined as one that meets one of the following three criteria:
1. occurring in a critical area or organ (for example, intracranial, intra-spinal,
intraocular, retroperitoneal, intra-articular or pericardial, intrauterine or
intramuscular with compartment syndrome),
2. causing a decrease in hemoglobin levels of 2 g/l (1.24 mmol/l) or more, or that
requires a transfusion of two or more units of whole blood or packed red blood
cells.
4. Lesions or conditions at increased risk of clinically significant bleeding,
including:
1. Previously diagnosed/treated VTE ≤ 28 days prior to randomization.
2. Active ulcer disease.
3. Diagnosed cerebral metastases.
4. Stroke within the prior 6 months.
5. History of central nervous system (CNS) or intraocular bleeding.
5. Requirement of other anticoagulant therapy, dual antiplatelet therapy, daily
non-steroidal anti-inflammatory drugs, or other medications known to increase the
risk of bleeding.
Note: A daily dose of ≤100 mg of aspirin and single agent clopidogrel are permitted
6. Acute or chronic renal insufficiency with Creatinine clearance < 30 ml / min.
7. Platelet count < 80.000 /ml at the time of inclusion.
8. Severe liver insufficiency as defined by clinical manifestations of ascites,
cirrhosis, encephalopathy and/or jaundice and/or biochemical abnormalities in liver
function tests including:
1. elevated levels of total bilirubin (> 2 times the upper limit normal [ULN]),
2. elevated liver transaminases (> 2 times the ULN; > 5 in case of hepatic
metastasis).
9. Participating in another study of an investigational agent at the time of
enrollment. Note: Use of an experimental regimen of an approved product is not cause
for exclusion.
10. Patients who weigh < 50 Kg.
11. Women of childbearing potential (WOCBP), must provide a negative serum or urine
pregnancy test at screening. Women breastfeeding are not eligible.
Note: A pregnancy test is performed on WOCBP as per standard of care for patients
undergoing anticancer treatments.
12. Any underlying medical or psychiatric disorder, which, in the opinion of the
investigator, makes the administration of tinzaparin unsafe or interferes with the
informed consent process or trial procedures.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Hospital Clínico Universitario de Santiago CHUS
Address:
City:
Santiago De Compostela
Zip:
15706
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Responsible person Designated by the Sponsor
Phone:
+34 93 434 44 12
Email:
investigacion@mfar.net
Investigator:
Last name:
Principal Investigator Designated by the sponsor, M.D.
Email:
Principal Investigator
Facility:
Name:
Hospital Público Verge dels Lliris
Address:
City:
Alcoy
Zip:
03804
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Responsible person Designated by the Sponsor
Phone:
+34 93 434 44 12
Email:
investigacion@mfar.net
Investigator:
Last name:
Principal Investigator Designated by the sponsor, M.D.
Email:
Principal Investigator
Facility:
Name:
Hospital Universitario Son Espases
Address:
City:
Palma De Mallorca
Zip:
07120
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Responsible person Designated by the Sponsor
Phone:
+34 93 434 44 12
Email:
investigacion@mfar.net
Investigator:
Last name:
Principal Investigator Designated by the Sponsor, M.D.
Email:
Principal Investigator
Facility:
Name:
ICO (Institut Català d'Oncologia) de Badalona
Address:
City:
Badalona
Zip:
08916
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Responsible person Designated by the Sponsor
Phone:
+34 93 434 44 12
Email:
investigacion@mfar.net
Investigator:
Last name:
Principal Investigator Designated by the Sponsor, M.D.
Email:
Principal Investigator
Facility:
Name:
Institut Català d'Oncologia L'Hospitalet
Address:
City:
L'Hospitalet De Llobregat
Zip:
08908
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Responsible person Designated by the Sponsor
Phone:
+34 93 434 44 12
Email:
investigacion@mfar.net
Investigator:
Last name:
Principal Investigator Designated by the sponsor, M.D.
Email:
Principal Investigator
Facility:
Name:
Consorcio Corporación Sanitaria Parc Taulí
Address:
City:
Sabadell
Zip:
08208
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Responsible person Designated by the Sponsor
Phone:
+34 93 434 44 12
Email:
investigacion@mfar.net
Investigator:
Last name:
Principal Investigator Designated by the Sponsor, M.D.
Email:
Principal Investigator
Facility:
Name:
Hospital Universitario Marqués de Valdecilla
Address:
City:
Santander
Zip:
39008
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Responsible person Designated by the Sponsor
Phone:
+34 93 434 44 12
Email:
investigacion@mfar.net
Investigator:
Last name:
Principal Investigator Designated by the Sponsor, M.D.
Email:
Principal Investigator
Facility:
Name:
Hospital General La Mancha Centro
Address:
City:
Alcázar De San Juan
Zip:
13600
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Responsible person Designated by the Sponsor
Phone:
+34 93 434 44 12
Email:
investigacion@mfar.net
Investigator:
Last name:
Principal Investigator Designated by the Sponsor, M.D.
Email:
Principal Investigator
Facility:
Name:
Hospital Univ. de Jerez de la Frontera
Address:
City:
Jerez De La Frontera
Zip:
11407
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Responsible person Designated by the Sponsor
Phone:
+34 93 434 44 12
Email:
investigacion@mfar.net
Investigator:
Last name:
Principal Investigator Designated by the Sponsor, M.D.
Email:
Principal Investigator
Facility:
Name:
Hospital Universitario Príncipe de Asturias (HUPA) de Alcalá de Henares
Address:
City:
Alcalá De Henares
Zip:
28805
Country:
Spain
Status:
Not yet recruiting
Contact:
Last name:
Responsible person Designated by the Sponsor
Phone:
+34 93 434 44 12
Email:
investigacion@mfar.net
Investigator:
Last name:
Principal Investigator Designated by the Sponsor, M.D.
Email:
Principal Investigator
Facility:
Name:
Hospital Universitario De Móstoles
Address:
City:
Móstoles
Zip:
28935
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Responsible person Designated by the Sponsor
Phone:
+34 93 434 44 12
Email:
investigacion@mfar.net
Investigator:
Last name:
Principal Investigator Designated by the Sponsor, M.D.
Email:
Principal Investigator
Facility:
Name:
Hospital Infanta Cristina (Parla)
Address:
City:
Parla
Zip:
28981
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Responsible person Designated by the Sponsor
Phone:
+34 93 434 44 12
Email:
investigacion@mfar.net
Investigator:
Last name:
Principal Investigator Designated by the Sponsor, M.D.
Email:
Principal Investigator
Facility:
Name:
Hospital Universitario Infanta Elena
Address:
City:
Valdemoro
Zip:
28342
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Responsible person Designated by the Sponsor
Phone:
+34 93 434 44 12
Email:
investigacion@mfar.net
Investigator:
Last name:
Principal Investigator Designated by the Sponsor, M.D.
Email:
Principal Investigator
Facility:
Name:
Hospital Costa del Sol de Marbella
Address:
City:
Marbella
Zip:
29603
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Responsible person Designated by the Sponsor
Phone:
+34 93 434 44 12
Email:
investigacion@mfar.net
Investigator:
Last name:
Principal Investigator Designated by the sponsor, M.D.
Email:
Principal Investigator
Facility:
Name:
Hospital Obispo Polanco De Teruel
Address:
City:
Teruel
Zip:
44002
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Responsible person Designated by the Sponsor
Phone:
+34 93 434 44 12
Email:
investigacion@mfar.net
Investigator:
Last name:
Principal Investigator Designated by the Sponsor, M.D.
Email:
Principal Investigator
Facility:
Name:
Complejo Hospitalario Universitario de A Coruña (CHUAC)
Address:
City:
A Coruña
Zip:
15006
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Responsible person Designated by the sponsor
Phone:
+34 93 434 44 12
Email:
investigacion@mfar.net
Investigator:
Last name:
Principal Investigator Designated by the sponsor, M.D.
Email:
Principal Investigator
Facility:
Name:
Centro Oncológico de Galicia (A coruña)
Address:
City:
A coruña
Zip:
15009
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Responsible person Designated by the Sponsor
Phone:
+34 93 434 44 12
Email:
investigacion@mfar.net
Investigator:
Last name:
Principal Investigator Designated by the Sponsor, M.D.
Email:
Principal Investigator
Facility:
Name:
Complejo Hospitalario Universitario de Ferrol ( Arquitecto Macide)
Address:
City:
A Coruña
Zip:
15405
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Responsible person Designated by the Sponsor
Phone:
+34 93 434 44 12
Email:
investigacion@mfar.net
Investigator:
Last name:
Principal Investigator Designated by the Sponsor, M.D.
Email:
Principal Investigator
Facility:
Name:
Hospital de la Santa Creu i Sant Pau
Address:
City:
Barcelona
Zip:
08025
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Responsible person Designated by the Sponsor
Phone:
+34 93 434 44 12
Email:
investigacion@mfar.net
Investigator:
Last name:
Principal Investigator Designated by the sponsor, M.D.
Email:
Principal Investigator
Facility:
Name:
Hospital Clinic Barcelona
Address:
City:
Barcelona
Zip:
08036
Country:
Spain
Status:
Not yet recruiting
Contact:
Last name:
Responsible person Designated by the Sponsor
Phone:
+34 93 434 44 12
Email:
investigacion@mfar.net
Investigator:
Last name:
Principal Investigator Designated by the Sponsor, M.D.
Email:
Principal Investigator
Facility:
Name:
Hospital General Virgen de la Luz de Cuenca
Address:
City:
Cuenca
Zip:
16002
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Responsible person Designated by the Sponsor
Phone:
+34 93 434 44 12
Email:
investigacion@mfar.net
Investigator:
Last name:
Principal Investigator Designated by the Sponsor, M.D.
Email:
Principal Investigator
Facility:
Name:
Hospital Universitario Arnau de Vilanova de Lleida
Address:
City:
Lleida
Zip:
25198
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Responsible person Designated by the Sponsor
Phone:
+34 93 434 44 12
Email:
investigacion@mfar.net
Investigator:
Last name:
Principal Investigator Designated by the Sponsor, M.D.
Email:
Principal Investigator
Facility:
Name:
Hospital Universitario Lucus Augusti
Address:
City:
Lugo
Zip:
27003
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Responsible person Designated by the sponsor
Phone:
+34 93 434 44 12
Email:
investigacion@mfar.net
Investigator:
Last name:
Principal Investigator Designated by the sponsor, M.D.
Email:
Principal Investigator
Facility:
Name:
Hospital Clinico San Carlos
Address:
City:
Madrid
Zip:
28040
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Responsible person Designated by the Sponsor
Phone:
+34 93 434 44 12
Email:
investigacion@mfar.net
Investigator:
Last name:
Principal Investigator Designated by the Sponsor, M.D.
Email:
Principal Investigator
Facility:
Name:
Hospital Universitario 12 de Octubre
Address:
City:
Madrid
Zip:
28041
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Responsible person Designated by the Sponsor
Phone:
+34 93 434 44 12
Email:
investigacion@mfar.net
Investigator:
Last name:
Principal Investigator Designated by the sponsor, M.D.
Email:
Principal Investigator
Facility:
Name:
Hospital General Universitario Morales Meseguer
Address:
City:
Murcia
Zip:
30008
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Responsible person Designated by the sponsor
Phone:
+34 93 434 44 12
Email:
investigacion@mfar.net
Investigator:
Last name:
Principal Investigator Designated by the sponsor, M.D.
Email:
Principal Investigator
Facility:
Name:
Complejo Hospitalario Universitario De Ourense
Address:
City:
Ourense
Zip:
32005
Country:
Spain
Status:
Recruiting
Contact:
Last name:
A responsible person Designated by the sponsor
Phone:
+34 93 434 44 12
Email:
investigacion@mfar.net
Investigator:
Last name:
Mercedes Salgado, M.D.
Email:
Principal Investigator
Facility:
Name:
Complejo Hospitalario Universitario de Pontevedra
Address:
City:
Pontevedra
Zip:
36071
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Responsible person Designated by the Sponsor
Phone:
+34 93 434 44 12
Email:
investigacion@mfar.net
Investigator:
Last name:
Principal Investigator Designated by the Sponsor, M.D.
Email:
Principal Investigator
Facility:
Name:
Complejo Asistencial Universitario De Salamanca
Address:
City:
Salamanca
Zip:
37007
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Responsible person Designated by the Sponsor
Phone:
+34 93 434 44 12
Email:
investigacion@mfar.net
Investigator:
Last name:
Principal Investigator Designated by the Sponsor, M.D.
Email:
Principal Investigator
Facility:
Name:
Hospital Universitario Virgen del Rocio
Address:
City:
Sevilla
Zip:
41013
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Responsible person Designated by the Sponsor
Phone:
+34 93 434 44 12
Email:
investigacion@mfar.net
Investigator:
Last name:
Principal Investigator Designated by the Sponsor, M.D.
Email:
Principal Investigator
Facility:
Name:
Hospital General Universitario de Toledo
Address:
City:
Toledo
Zip:
45007
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Responsible person Designated by the Sponsor
Phone:
+34 93 434 44 12
Email:
investigacion@mfar.net
Investigator:
Last name:
Principal Investigator Designated by the Sponsor, M.D.
Email:
Principal Investigator
Facility:
Name:
Hospital General Universitario de Valencia
Address:
City:
Valencia
Zip:
46014
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Responsible person Designated by the Sponsor
Phone:
+34 93 434 44 12
Email:
investigacion@mfar.net
Investigator:
Last name:
Principal Investigator Designated by the Sponsor, M.D.
Email:
Principal Investigator
Facility:
Name:
Hospital Ribera Povisa
Address:
City:
Vigo
Zip:
36211
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Responsible person Designated by the sponsor
Phone:
+34 93 434 44 12
Email:
investigacion@mfar.net
Investigator:
Last name:
Principal Investigator Designated by the sponsor, M.D.
Email:
Principal Investigator
Facility:
Name:
Complejo Hospitalario Universitario de Vigo (Álvaro Cunqueiro)
Address:
City:
Vigo
Zip:
36312
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Responsible person Designated by the sponsor
Phone:
+34 93 434 44 12
Email:
investigacon@mfar.net
Investigator:
Last name:
Principal Investigator Designated by the sponsor, M.D.
Email:
Principal Investigator
Facility:
Name:
Complejo Asistencial de Zamora
Address:
City:
Zamora
Zip:
49022
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Responsible person Designated by the sponsor
Phone:
+34 93 434 44 12
Email:
investigacion@mfar.net
Investigator:
Last name:
Principal Investigator Designated by the sponsor, M.D.
Email:
Principal Investigator
Start date:
March 2, 2023
Completion date:
March 2025
Lead sponsor:
Agency:
Galician Research Group on Digestive Tumors
Agency class:
Other
Collaborator:
Agency:
LEO Pharma
Agency class:
Industry
Source:
Galician Research Group on Digestive Tumors
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05625932
