Doxorubicin Eluting Intra-arterial Embolization for Aggressive Desmoid Fibromatosis
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|ClinicalTrials.gov Identifier: NCT03966742|
Recruitment Status : Recruiting
First Posted : May 29, 2019
Last Update Posted : May 30, 2019
|Condition or disease||Intervention/treatment||Phase|
|Desmoid Desmoid Fibromatosis of Skin Desmoid Neoplasm of Chest Wall Desmoid Tumor Caused by Somatic Mutation Aggressive Fibromatoses Fibromatosis Desmoid Desmoid Fibromatosis||Procedure: Drug Eluting Bead Embolization (DEB) for Desmoid Fibromatosis||Phase 2|
Desmoid Fibromatoses (DF) are locally aggressive lesions associated with substantial morbidity and potentially mortality, due to invasion of adjacent neurovascular structures and vital organs. They have no potential for metastasis. Histologically, they are characterised by mature fibroblasts within a matrix of abundant fibrous stroma. While 5-15% of cases are seen in patients with Familial Adenomatous Polyposis (FAP) syndrome, the vast majority arise sporadically.
The etiology of Desmoids remains poorly understood and the therapeutic approaches in their management remain very diverse. For resectable lesions, surgery is recommended but reported cure rates range broadly from 12-80%. Systemic treatments range from non-steroidal anti-inflammatories and anti-estrogenic therapy to targeted tyrosine kinase inhibitors and cytotoxic chemotherapy, most commonly methotrexate, vinblastine and doxorubicin.
Doxorubicin is an anthracycline with demonstrated efficacy in treating desmoids at systemic IV doses of 50- 75mg/m2 over 3-4 week cycles. Extended use is limited by dose - dependent cardiotoxicity which can be seen in up to 36% of patients receiving doses in excess of 550mg/m2. Delayed cardiotoxicity is particularly common and less predictable among pediatric cancer survivors.
Selective trans-arterial chemo-embolization (TACE) is a method to achieve high tissue drug concentration with minimal systemic toxicity. Historically, this has been achieved by mixing doxorubicin with embolic agents such as lipiodol or gelatin sponge in the treatment of hepatocellular carcinoma (HCC).
Drug-eluting microbeads (DEB) ionically loaded with doxorubicin have shown sustained release in TACE target tissues with substantially lower serum drug concentrations when compared to lipiodol TACE.
The present study utilizes DEB's loaded with Doxorubicin delivered into the target DF tissue via selective arterial embolization by angiographic technique. This study follows a successful feasibility study.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||50 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||All patients|
|Masking:||None (Open Label)|
|Official Title:||Doxorubicin Eluting Intra-arterial Embolization for Aggressive Desmoid Fibromatosis|
|Actual Study Start Date :||October 11, 2018|
|Estimated Primary Completion Date :||October 2023|
|Estimated Study Completion Date :||October 2025|
Doxorubin-eluting particle embolization for treatment of Desmoid Fibromatosis.
Procedure: Drug Eluting Bead Embolization (DEB) for Desmoid Fibromatosis
Delivery of Doxorubicin selectively into Desmoid Fibromatosis utilizing its vascular supply as a conduit, and ionic loading the doxorubicin onto embolized particles as the drug delivery vehicle.
Maximal dose is 75 mg/m2 and at least 50 mg. The bead size is 75-300 Mµ in a 2 CC syringe.
- Objective response rate of tumor size. [ Time Frame: At baseline ; 6-10 weeks after each treatment ]Response to treatment. Measured by change in tumor size according to RECIST (Response Evaluation Criteria in Solid Tumors) version 1.1 criteria.
- Objective response rate of tumor biological activity. [ Time Frame: At baseline ; 6-10 weeks after each treatment ]Response to treatment. Tumor biological activity measured by change in MRI T2 signal intensity.
- Patient reported outcomes. [ Time Frame: At baseline ; 6-10 weeks after each treatment ]
Change in clinical symptoms measured by standard clinical patient questionnaires - EORTC QLQ-C30. (Quality of Life Questionnaire).
All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. Thus a high score for a functional scale represents a high level of functioning, a high score for the global health status / QoL represents a high QoL. Similarly, a high score for a symptom scale represents a high level of symptomatology.
- Adverse event profile (safety) [ Time Frame: At baseline ; 6-10 weeks ]Treatment safety measured by standard patient questionnaires and clinical evaluation using CTCAE (Common Terminology Criteria for Adverse Events) version 5.0.
- Pharmacokinetics of Doxorubicin [ Time Frame: 5 minutes, 30 minutes, 1 hour, 12 hours, 24 hours after treatment procedure ]Measurements of blood Doxorubicin concentration (mg/ml) over time, after treatment.
- Exploratory biomarkers [ Time Frame: At baseline ; 6-10 weeks ]Immunohistochemistry assay assessing the staining pattern (marked as negative to mildly or strongly positive) for: beta-catenin, keratin, SMA (smooth muscle actin). Ki-67 staining will be scored by percentage.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03966742
|Contact: Eldad Elnekave, MDfirstname.lastname@example.org|
|Rabin Medical Center||Recruiting|
|Contact: Eldad Elnekave, MD email@example.com|