Clinical trial NCT00951574: Prevention of Venous and Arterial Thromboembolism, in Cancer Patients Undergoing Chemotherapy, With a Low Molecular Weight Heparin (Nadroparin Calcium)
Official title: Prevention of Venous and Arterial Thromboembolism, in Cancer Patients Undergoing Chemotherapy, With a Low Molecular Weight Heparin (Nadroparin Calcium). A Randomized, Placebo-controlled, Double-blind, Multicenter Phase III Study.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Advanced Cancer
Metastatic Cancer
Keywords: thromboembolism
cancer
chemotherapy
low-molecular-weight-heparin
nadroparin
Lead sponsor: Italfarmaco
Sponsor class: INDUSTRY
First posted: 2009-08-04
Enrollment: 1166
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

Brief summary: In this phase III, multicenter study, 1200 patients with lung, breast, gastrointestinal (stomach, colon-rectum, pancreas), ovarian or head and neck cancer undergoing chemotherapy will be randomly assigned (at the beginning of cytotoxic therapy) in a 2:1 ratio and in double-blind conditions to a treatment with subcutaneous low molecular weight heparin (nadroparin calcium, one injection/day) or placebo for the overall duration of chemotherapy or up to a maximum of 4 months (+/- 10 days).


Eligibility criteria: INCLUSION CRITERIA:

* both sexes;aged\>18 years;
* suffering from different types of malignancies(lung, breast,gastric,colon- rectum,pancreatic,ovarian,head and neck cancer)undergoing systemic chemotherapy,
* having signed Informed Consent prior to initiation of any study procedure.

EXCLUSION CRITERIA:

* adjuvant and neo-adjuvant chemotherapy;
* objectively confirmed venous or arterial thromboembolism in the last three months;
* antithrombotic treatment for other indications;
* life expectancy of less than 3 months;
* Performance Status\>2(ECOG);
* active bleeding or bleedings in the last four weeks requiring hospitalization,transfusion or surgical intervention;
* bleeding diathesis(prothrombin time\<70% or activated partial thromboplastin time ratio\>1.3),or platelet count\<50x10\^9/L;
* cerebrovascular hemorrhage in the last six months;
* known active gastric or duodenal ulcer;
* known cerebral metastasis;
* cerebral aneurysm;
* III-IV grade diabetic retinopathy;
* severe and uncontrolled hypertension(systolic blood pressure\>180 mmHg or diastolic blood pressure\>110 mmHg);
* chronic atrial fibrillation;
* acute endocarditis;
* acute pancreatitis;
* known hypersensitivity to unfractionated heparin or LMWH;
* previous occurrence of heparin-induced thrombocytopenia;
* renal impairment (dependent on dialysis or creatinine higher than 2.5mg%);
* liver insufficiency (alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase levels\>3 times the upper limit of the normal ranges and/or total bilirubin \>3.0 mg/ml);
* pregnancy or childbearing potential without adequate contraception;
* treatment with other investigational drugs or patient inclusion in other clinical trials;
* patients who are unable to fulfill the study requirements in terms of visits/compliance to treatment.

Primary outcomes:
measure: Cumulative incidence of symptomatic venous and arterial thromboembolism, in patients with metastatic or locally advanced solid tumors undergoing chemotherapy
timeFrame: Events occurring during the four months of treatment plus 10 days
Secondary outcomes:
measure: Survival, at the end of study treatment
timeFrame: Events occurring during the four months of treatment plus 10 days
measure: Response to chemotherapy
timeFrame: Events occurring during the four months of treatment plus 10 days
measure: For patients with central venous catheters (CVC), complications of possible thrombotic origin, such as malfunction or requirement of CVC removal
timeFrame: Events occurring during the four months of treatment plus 10 days
measure: Superficial thrombophlebitis of lower limbs
timeFrame: Events occurring during the four months of treatment plus 10 days
measure: Asymptomatic thromboembolic events diagnosed during tests performed for other purposes
timeFrame: Events occurring during the four months of treatment plus 10 days
measure: Safety (major bleeding, minor bleeding, other adverse events)
timeFrame: Events occurring during the four months of treatment plus 48 hours
Other outcomes:
Locations:
city: Fabriano
country: Italy
facility: Medical Oncology Department
state: Ancona
city: Treviglio
country: Italy
facility: Medical Oncology Department
state: Bergamo
city: San Giovanni Rotondo
country: Italy
facility: Casa Sollievo dell Sofferenza
state: Foggia
city: Taormina
country: Italy
facility: Medical Oncology Department
state: Messina
city: Legnano
country: Italy
facility: Medical Oncology Department
state: Milano
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
state: Milano
city: Camposampiero
country: Italy
facility: Medical Oncology Department
state: Padova
city: Città di Castello
country: Italy
facility: Medical Oncology Department
state: Perugia
city: Todi
country: Italy
facility: Medical Oncology Department
state: Perugia
city: Orbassano
country: Italy
facility: Medical Oncology Department San Luigi Hospital
state: Torino
city: Bari
country: Italy
facility: Medical Oncology Department Oncology Institute
city: Bergamo
country: Italy
facility: Medical Oncology Unit
city: Bologna
country: Italy
facility: Medical Oncology Department - Bellaria Hospital
city: Cagliari
country: Italy
facility: Medical Oncology Department - Businco Hospital
city: Cagliari
country: Italy
facility: Medical Oncology Department University of Cagliari
city: Catanzaro
country: Italy
facility: Medical Oncology Department
city: Cosenza
country: Italy
facility: Medical Oncology Department
city: Cremona
country: Italy
facility: Medical Oncology Department
city: Ferrara
country: Italy
facility: Medical Oncology Department
city: Firenze
country: Italy
facility: Medical Oncology Department Careggi Hospital
city: Forlì
country: Italy
facility: Cancer institute of Romagna
city: Latina
country: Italy
facility: Medical Oncology Department
city: Lecce
country: Italy
facility: Medical Oncology Department
city: Lucca
country: Italy
facility: Medical Oncology Department
city: Milano
country: Italy
facility: University Bicocca
city: Milano
country: Italy
facility: Medical Oncology Department Fatebenefratelli Hospital
city: Milano
country: Italy
facility: Medical Oncology Department Policlinico
city: Milano
country: Italy
facility: Gynecology Oncology INT
city: Milano
country: Italy
facility: Medical Oncology Department San Carlo Hospital
city: Padova
country: Italy
facility: Medical Oncology Department Istituto Oncologico Veneto
city: Palermo
country: Italy
facility: Medical Oncology Department
city: Pavia
country: Italy
facility: Salvatore Maugeri Foundation
city: Perugia
country: Italy
facility: Medical Oncology Department
city: Piacenza
country: Italy
facility: Hematology and Oncology Department
city: Pisa
country: Italy
facility: Medical Oncology Department - University of Pisa
city: Ravenna
country: Italy
facility: Medical Oncology Department
city: Reggio Emilia
country: Italy
facility: Medical Oncology Department
city: Roma
country: Italy
facility: Medical Oncology Department - S Filippo Hospital
city: Roma
country: Italy
facility: Medical Oncology Department Regina Elena Institute
city: Rome
country: Italy
facility: Medical Oncology Department 3 Regina Elena Cancer Institute
city: Rome
country: Italy
facility: Onco-gynecology Department - Catholic University
city: Sassari
country: Italy
facility: Medical Oncology Department
city: Terni
country: Italy
facility: Medical Oncology Department
city: Torino
country: Italy
facility: Oncology Department Molinette Hospital
city: Varese
country: Italy
facility: Medical Oncology Department
city: Viterbo
country: Italy
facility: Medical Oncology Department
Study officials:
affiliation: Internal and Vascular Medicine University of Perigia (Italy)
name: Giancarlo Agnelli, MD
role: STUDY_CHAIR
References:
citation: Rutjes AW, Porreca E, Candeloro M, Valeriani E, Di Nisio M. Primary prophylaxis for venous thromboembolism in ambulatory cancer patients receiving chemotherapy. Cochrane Database Syst Rev. 2020 Dec 18;12(12):CD008500. doi: 10.1002/14651858.CD008500.pub5.
citation: Barni S, Labianca R, Agnelli G, Bonizzoni E, Verso M, Mandala M, Brighenti M, Petrelli F, Bianchini C, Perrone T, Gasparini G. Chemotherapy-associated thromboembolic risk in cancer outpatients and effect of nadroparin thromboprophylaxis: results of a retrospective analysis of the PROTECHT study. J Transl Med. 2011 Oct 20;9:179. doi: 10.1186/1479-5876-9-179.
citation: Agnelli G, Gussoni G, Bianchini C, Verso M, Mandala M, Cavanna L, Barni S, Labianca R, Buzzi F, Scambia G, Passalacqua R, Ricci S, Gasparini G, Lorusso V, Bonizzoni E, Tonato M; PROTECHT Investigators. Nadroparin for the prevention of thromboembolic events in ambulatory patients with metastatic or locally advanced solid cancer receiving chemotherapy: a randomised, placebo-controlled, double-blind study. Lancet Oncol. 2009 Oct;10(10):943-9. doi: 10.1016/S1470-2045(09)70232-3. Epub 2009 Aug 31.