Tinzaparin And Biomarkers After Neoadjuvant Treatment of Ovarian Cancer

NCT ID: NCT05284552

Last Updated: 2025-02-27

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-07-12
• Study Completion Date: 2026-12-31

Brief Summary

Background:

Previous findings have indicated antineoplastic properties of tinzaparin (Innohep®), a commonly used anti-coagulant. Earlier studies have mainly investigated the antineoplastic effects of tinzaparin in animal models and in human cell-lines. In this pilot study the aim is to examine the potential antitumoral effects of tinzaparin in vivo in women with epithelial ovarian cancer (EOC).

Study objectives:

Primary objective: The primary objective of the study is to evaluate the effects of tinzaparin on changes in levels of CA-125 in EOC patients who receive neoadjuvant chemotherapy (NACT).

Secondary objectives: The secondary objective of the study is to explore the impact of tinzaparin on the dynamic of a spectrum of immunological and coagulation factors in EOC patients who receive NACT. Besides, the compliance of tinzaparin injections and adverse events caused by tinzaparin will be described.

Detailed Description

This is an open randomized controlled clinical pilot trial (Phase II). The study includes women with the International Federation of Obstetrics and Gynecology (FIGO) stage III-IV EOC selected for neoadjuvant chemotherapy (NACT) and without signs of thromboembolic disease or ongoing treatment of thromboembolic disease. The women will be allocated 1:1 to treatment with tinzaparin 4500 IU/8000 IU (dose depending on woman's weight) subcutaneously once daily or no tinzaparin. The treatment group starts tinzaparin when the primary treatment (chemotherapy) starts. The control group will not receive tinzaparin or other low molecular weight heparin preparations. The NACT consists of carboplatin and paclitaxel, given according to the standard regimen with cycle repeats every 21 days. Pre-treatment, before every cycle of chemotherapy, before delayed primary debulking surgery (DPDS) and three weeks after the last cycle of chemotherapy venous blood samples will be taken for measuring the biomarkers hemoglobin, platelets, leucocytes, C-reactive protein (CRP), albumin, cancer antigen-125 (CA-125), Tissue Factor, D-dimer, soluble P-selectin, thrombin-antithrombin complex and thrombin generation potential. Furthermore, a panel of 92 inflammation-associated proteins will be analyzed by a by a high-sensitivity Proximity Extension Assay at baseline, visit 5 and visit 8 or 9. After three cycles of NACT, the patient will be evaluated clinically and with imaging diagnostics in order to determine whether the patient should undergo DPDS. In the investigators´ setting, > 80% of patients receiving NACT for EOC undergo DPDS. After DPDS, all patients will be treated with tinzaparin for 28 days according to clinical practice concerning postoperative thromboembolic prophylaxis and thereafter continue the chemotherapy for additional two-three courses. The participants who were allocated to tinzaparin during the NACT will continue the tinzaparin after ending the postoperative thromboembolic prophylactic tinzaparin treatment for additional 2-3 courses. The biomarkers will be measured preoperatively and four weeks postoperatively after DPDS and then before each course of chemotherapy given during the primary treatment. The women who do not undergo surgery will remain included in the study for the following three cycles of chemotherapy. Thus, the total study period constitutes 22-29 weeks.

Conditions

Epithelial Ovarian Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Intervention Arm

Drug: Tinzaparin (Innohep®), solution for injection. Administration form: Subcutaneous injection. Dosage: 4500 IU (for subjects weighing below 90 kg) or 8000 IU (for subjects weighing 90 kg and above) daily for 21-28 weeks.

Group Type: EXPERIMENTAL

Tinzaparin Injectable Solution

Intervention Type: DRUG

Subcutaneous injection

Control Arm

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Tinzaparin Injectable Solution

Subcutaneous injection

Intervention Type: DRUG

Other Intervention Names

Innohep®

Eligibility Criteria

Inclusion Criteria

• The subject has given written consent to participate in the study.
• Age 18 and above
• Epithelial ovarian, fallopian tube or peritoneal cancer, or abdominal cancer where a biopsy indicates an origin from the ovary, fallopian tube or peritoneum.
• Histology diagnosis of either high grade serous carcinoma, endometrioid carcinoma or clear cell carcinoma.
• FIGO stage III-IV disease.
• Selected for NACT with platinum double regimen at a multidisciplinary conference at Department of Oncology at Linköping University Hospital
• Receive treatment at either of the University Hospital in Linköping, or the hospitals in Jönköping (Ryhov Hospital), Eksjö (Highland Hospital, Eksjö), Västervik (Västervik hospital), Kalmar (County Hospital, Kalmar), Värnamo (Värnamo hospital).
• Planned for platinum doublet regimen.
• Prior to start of NACT pregnancy should be ruled out by menstrual history or in unclear cases by a urine human chorionic gonadotropin (hCG) test.
• Women of childbearing potential should use a safe birth control method (combined hormonal contraception, progesterone only hormonal contraception, intra uterine device, bilateral tubal occlusion, vasectomized partner, sexual abstinence, male or female condom, diaphragm with spermicide).
• World Health Organization (WHO) Performance Status 0-1
• Weight 50-150 kg
• CA-125-level ≥250 kIU/L at diagnosis

Exclusion Criteria

• Concomitant treatment with heparins, low molecular weight heparins, warfarin or nonvitamin K antagonist oral anticoagulants. Platelet inhibitors are allowed.
• Treatment with heparins, low molecular weight heparins or non-vitamin K antagonist oral anticoagulants within the last year.
• Known or suspected allergies against any product included in the study
• Ongoing pregnancy, independent of gestational age. Breastfeeding or planned pregnancy
• EOC disclosed at Cesarean section
• Abdominal surgery or other major surgery within the last year
• Mental inability, reluctance or language difficulties that result in difficulty understanding the meaning of study participation
• Treatment or disease which, according to the investigator, can affect treatment or study results
• Known brain metastasis
• Participation or recent participation (within the last 30 days) in a clinical study with an investigational product
• Ongoing treatment of thromboembolic disease.
• Thromboembolic disease within the last year.
• Hypersensitivity to the active substance (tinzaparin) or any of the excipients.
• Serious hemorrhage or conditions predisposing to serious hemorrhage. Serious hemorrhage is defined as fulfilling any one of these three criteria:

1. occurs in a critical area or organ (e.g. intracranial, intraspinal, intraocular, retroperitoneal, intra-articular or pericardial, intra-uterine or intramuscular with compartment syndrome),

2. causes a fall in hemoglobin level of 20 g/L (1.24 mmol/L) or more, or

3. leads to transfusion of two or more units of whole blood or red blood cells.

• Severe coagulation disorder.
• Acute gastro duodenal ulcer.
• Septic endocarditis.
• Previous heparin-induced thrombocytopenia.
• WHO Performance Status >1.
• Platinum single regimen
• Estimated glomerular filtration rate (E-GFR) <30ml/min (analyzed no more than 14 days before start of treatment with investigational product)
• Platelets <100 x10^9/L (analyzed no more than 14 days before start of treatment with investigational product)
• Treatment for other known malignancy within the last year (except basal cell carcinoma)

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Region Jönköping County

OTHER_GOV

Sponsor Role: collaborator

Västervik Hospital

OTHER

Sponsor Role: collaborator

Vastra Gotaland Region

OTHER_GOV

Sponsor Role: collaborator

Region Västerbotten

OTHER_GOV

Sponsor Role: collaborator

University Hospital, Linkoeping

OTHER

Sponsor Role: lead

Responsible Party

Preben Kjolhede, MD, professor

Professor, senior consultant

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Preben Kjölhede, MD, PhD

Role: STUDY_CHAIR

University Hospital, Linkoeping

Gabriel Lindahl, MD, PhD

Role: STUDY_CHAIR

University Hospital, Linkoeping

Anna-Clara Spetz Holm, MD, PhD

Role: STUDY_CHAIR

University Hospital, Linkoeping

Anna Karlsson, MD

Role: STUDY_CHAIR

University Hospital, Linkoeping

Locations

Department of Obstetrics and Gynecology, Highland Hospital

Eksjö, , Sweden

Site Status: RECRUITING

Department of Oncology, Sahlgrenska University Hospital

Gothenburg, , Sweden

Site Status: RECRUITING

Department of Obstetrics and Gynecology, Ryhov County Hospital

Jönköping, , Sweden

Site Status: RECRUITING

Department of Oncology, Linköping University Hospital

Linköping, , Sweden

Site Status: RECRUITING

Department of Obstetrics and Gynaecology, Norrland University Hospital

Umeå, , Sweden

Site Status: RECRUITING

Department of Obstetrics and Gynecology, Värnamo Hospital

Värnamo, , Sweden

Site Status: RECRUITING

Department of Obstetrics and Gynecology, Västervik Hospital

Västervik, , Sweden

Site Status: RECRUITING

Department of Obstetrics and Gynecology, University Hospital

Linköping, Östergötland County, Sweden

Site Status: ACTIVE_NOT_RECRUITING

Countries

Sweden

Central Contacts

Preben Kjölhede, MD, PhD

Role: CONTACT

preben.kjolhede@regionostergotland.se

+46101030000 ext. 3187

Anna Karlsson, MD

Role: CONTACT

anna.br.karlsson@regionostergotland.se

+46101030000 ext. 3117

Facility Contacts

Malena Tiefenthal Thrane, MD

Role: primary

malena.tiefenthal.thrane@rjl.se

+46102410000

Karin Bergmark, MD, PhD

Role: primary

Karin.Bergmark@vgregion.se

+46313421000

Laila Falknäs, MD

Role: primary

laila.falknas@rjl.se

+46102410000

Gabriel Lindahl, MD, PhD

Role: primary

gabriel.lindahl@regionostergotland.se

+46101030000

Ulrika Ottander, MD, PhD

Role: primary

Ulrika.Ottander@umu.se

+46907850000

Shefqet Halili, MD

Role: primary

shefqet.halili@rjl.se

+46102410000

Anders Rosenmüller, MD

Role: primary

anders.rosenmuller@regionkalmar.se

+4649086000

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2021-000135-31

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

The TABANETOC-trial

Identifier Type: -

Identifier Source: org_study_id