imPaCT-PRO: The Impact of Thromboprophylaxis on Progression Free Survival of Patients With Advanced Pancreatic Cancer

Sponsor

Michalis Karamouzis (Other)

Overall Status

Recruiting

CT.gov ID

NCT05178628

Collaborator

(none)

450

Enrollment

Locations

Arms

34.7

Anticipated Duration (Months)

225

Patients Per Site

6.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a prospective, randomized, multicenter, open-label, blinded-endpoint Phase III clinical trial to investigate the impact of thromboprophylaxis using innohep, beyond anticoagulation in the improvement of the clinical outcomes in active pancreatic cancer patients receiving systemic anti-neoplasmatic treatment. The number of patients that will be enrolled is 450. The enrollment period is 24 months and the follow up period is 10 months.

Condition or Disease	Intervention/Treatment	Phase
Pancreatic Cancer Thromboembolism	Drug: Innohep Drug: Chemotherapy: Gemcitabine + Nab-Paclitaxel	Phase 3

Detailed Description

Pancreatic cancer (PC) has the worst prognosis of any malignancy. Venous thromboembolism (VTE) occurs in 1:5 PC patients and is associated with significantly reduced progression-free survival (PFS). Phase III randomised controlled trials concluded that targeted thromboprophylaxis with low molecular weight heparins (LMWH) resulted in an 82% reduction in the relative risk of VTE without increasing major bleeding events, and that 11 patients were needed to be treated to prevent one VTE during chemotherapy. The benefits observed in the many of reported studies could not be accounted for by VTE prevention alone. Numerous experimental studies have demonstrated the antitumour, anti-metastatic and chemo-resistance reversal effect of LMWH.

The vast majority of the so far published evidence assessing the efficacy and safety of VTE prevention in ambulatory cancer patients is based on mixed patient populations with various types of cancers. Thus, current studies do not allow to estimate the real effect of long-term prophylaxis on clinical outcomes in selected homogeneous high-thrombotic risk patients.

An approach more specific to PC and restricted to advanced or metastatic patients is a modern and attractive strategy to assess the benefit of thromboprophylaxis in VTE prevention and beyond anticoagulation.

The objective of the imPaCT-PRO trial is to investigate the impact of thromboprophylaxis beyond anticoagulation in the improvement of the clinical outcomes in active PC patients receiving systemic anti-neoplasmatic treatment.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

450 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Prospective, randomized, multicenter, open-label, blinded-endpoint Phase III clinical trialProspective, randomized, multicenter, open-label, blinded-endpoint Phase III clinical trial

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

The Impact of Thromboprophylaxis on Progression Free Survival of Patients With Advanced Pancreatic Cancer: The Pancreatic Cancer & Tinzaparin Prospective (imPaCT-PRO) Study

Actual Study Start Date :

Feb 10, 2022

Anticipated Primary Completion Date :

Dec 31, 2024

Anticipated Study Completion Date :

Dec 31, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Patients treated with Innohep® and chemotherapy The patients in this arm will receive Innohep and chemotherapy with Gemcitabine + Nab-Paclitaxel (NabG) as per clinical practice.	Drug: Innohep Patients will receive Tinzaparin sodium 20.000 Anti-Xa IU/ml in prefilled syringes. Administered at 175 Anti-Xa IU/Kgr of body weight, subcutaneously, once daily Other Names: Tinzaparin sodium
Active Comparator: Patients treated with chemotherapy The patients in this arm will receive chemotherapy with Gemcitabine + Nab-Paclitaxel (NabG) as per clinical practice.	Drug: Chemotherapy: Gemcitabine + Nab-Paclitaxel All patients will receive chemotherapy per clinical practice

Arm

Intervention/Treatment

Experimental: Patients treated with Innohep® and chemotherapy

The patients in this arm will receive Innohep and chemotherapy with Gemcitabine + Nab-Paclitaxel (NabG) as per clinical practice.

Drug: Innohep

Patients will receive Tinzaparin sodium 20.000 Anti-Xa IU/ml in prefilled syringes. Administered at 175 Anti-Xa IU/Kgr of body weight, subcutaneously, once daily

Other Names:

Tinzaparin sodium

Active Comparator: Patients treated with chemotherapy

The patients in this arm will receive chemotherapy with Gemcitabine + Nab-Paclitaxel (NabG) as per clinical practice.

Drug: Chemotherapy: Gemcitabine + Nab-Paclitaxel

All patients will receive chemotherapy per clinical practice

Outcome Measures

Primary Outcome Measures

PFS of patients [12 months]
PFS of patients receiving thromboprophylaxis with tinzaparin, in comparison with the PFS of patients not receiving such prevention
The number of VTE events during the trial [12 months]
All objectively confirmed VTE events during the study per treatment arm including symptomatic distal deep vein thrombosis (DVT), symptomatic or incidental proximal DVT (including iliac and cava thrombosis), symptomatic or incidental pulmonary embolism (PE) or both DVT and PE (co-primary endpoint) or fatal PE or vein thrombosis of rare localisation (i.e., splanchnic vein or cerebral vein thrombosis).

Secondary Outcome Measures

% of patients experiencing at least one major bleeding event [Through study completion, an average of 2 years]
% of patients experiencing at least one major bleeding event, according to the International Society on Thrombosis and Haemostasis (ISTH) criteria during the study per treatment arm.
% of patients experiencing any bleeding event [Through study completion, an average of 2 years]
% of patients experiencing any bleeding event, including major, clinically relevant non-major bleeding (CRNMB) and minor bleeding events during the study per treatment arm.
VTE events [Through study completion, an average of 2 years]
Incidence of VTE events, per event type, during the study per treatment arm
Patients with complete or partial response [Through study completion, an average of 2 years]
ORR, defined as the percentage of patients with complete response (CR) or partial response (PR) based on RECIST criteria
Change from baseline in QoL [at 4 and 10 months]
Change from baseline in QoL at 4 months and 10 months per treatment arm. QoL will be determined with the EORTC QLQ-C30 version 3.0. and EORTC QOL-PAN26 questionnaires according to the corresponding scoring manual

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Advanced or metastatic PC (confirmed by the recommended histological and imaging methods).
Age ≥ 18 years.
Planning to start 1st line chemotherapy with NabG.
Eastern Cooperative Group (ECOG) 0-2.
Life expectancy >6 months.
Written informed consent.

Exclusion Criteria:

Subjects with contraindication to receive anticoagulant:
Any hypersensitivity to anticoagulant or excipients.
History of heparin-induced thrombocytopenia type II (HIT II).
Active major bleeding or pre-diathesis for major bleeding
Septic endocarditis.
Creatinine clearance <20 mL/min according to Cockcroft-Gault formula.
Platelet count < 50 G/L at inclusion.
Hepatic dysfunction defined as at least one of the following: AST and/or ALT > 5 x ULN, bilirubin > 2 x ULN.
Recent (< 1 month) oncological surgery, major abdominal or thoracic surgery, major orthopedic surgery, vascular surgery.
Recent (< 1 month) acute coronary syndrome or any other arterial thrombosis, thrombotic or hemorrhagic stroke.
Patients on chronic anticoagulation or on dual anti-platelet treatment.
Pregnancy/lactation or insufficient contraception during the study and up to 3 months after the study.
Severe concomitant disease that as per investigator's judgement is not compatible with participation in the study.