Toremifene in Desmoid Tumor: Prospective Clinical Trial and Identification of Potential Molecular Targets

Study Overview
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Brief Summary
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This is a prospective study evaluating the activity and the safety of toremifene in patients with primary or recurrent sporadic DTs. Patients will be enrolled after the histological confirmation of DTs on biopsy Patients will start at 60 mg daily and dose-escalate to 180 mg upon progression. Disease assessment will be performed by contrast-enhanced MRI or CT scan, pain evaluation by a visual analog scale (VAS) every 3 months for the first and second year, twice yearly thereafter. Response will be evaluated either by RECIST and/or symptomatic relief.

Detailed Description
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This is a prospective study evaluating the activity and the safety of toremifene in patients with primary or recurrent sporadic DTs. Patients will be enrolled after the histological confirmation of DTs on biopsy performed at the investigators institution or after the pathological review of tissue specimen obtained via needle biopsy or surgical excision (in case of recurrence) performed elsewhere. A new biopsy will be performed if the amount of tissue will not be sufficient for immunohistochemical analysis. Patients will start at 60 mg daily and dose-escalate to 180 mg upon progression. Disease assessment will be performed by contrast-enhanced MRI or CT scan, pain evaluation by a visual analog scale (VAS) every 3 months for the first and second year, twice yearly thereafter. Response will be evaluated either by RECIST and/or symptomatic relief.

Official Title
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Toremifene in Desmoid Tumor: Prospective Clinical Trial and Identification of Potential Molecular Targets

Conditions
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Desmoid Type-fibromatosis

Intervention / Treatment
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* Drug: Toremifene


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients (age > 18 years) with primary or locally recurrent, sporadic or FAP associated, desmoid fibromatosis Histologically documented diagnosis of DF At least one measurable site of disease at CT or MRI scans, which has not been previously embolised or irradiated Progressive disease demonstrated at contrast-enhanced MRI or CT scan by Response Evaluation Criteria in Solid Tumors (RECIST) Radiologic or clinical evidence of PD in the previous 6 months. Radiologic PD will be defined according to RECIST ECOG Performance status: 0-2 Prior hormonal therapy, chemotherapy, or molecular targeted therapies are allowed Adequate end organ function, defined as the following: total bilirubin < 1.5 x ULN, SGOT and SGPT < 2.5 x UNL (or < 5 x ULN if hepatic metastases are present), creatinine < 1.5 x ULN, ANC > 1.5 x 109/L, platelets > 100 x 109/L Female patients of child-bearing potential must have negative pregnancy test within 7 days before initiation of study drug dosing. Post menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Male and female patients of reproductive potential must agree to employ an effective barrier method of birth control throughout the study and for up to 3 months following discontinuation of study drug Life expectancy of at least 6 months Written, voluntary, informed consent. Exclusion Criteria: Previous history of deep vein thrombosis Evidence of prolonged QTc >480 msec (using Bazetts correction, for which the formula is: QTc = QT/√RR) or history of familial long QT syndrome Previous arrhythmia Clinically significant bradycardia Endometrial hyperplasia Hepatic insufficiency Other concurrent hormonal therapy, including hormonal contraceptives Patient has received any other investigational agents within 28 days of first day of study drug dosing. - Female patients who are pregnant or breast-feeding Patient has a severe and/or uncontrolled medical disease Patient has a known diagnosis of human immunodeficiency virus (HIV) infection Patient received chemotherapy within 4 weeks prior to study entry Patient had a major surgery within 2 weeks prior to study entry.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Toremifene treatment<br>Patients will receive 60 mg daily of Toremifene and the dose will be escalated to 180 mg daily in case of progression | Drug: Toremifene<br>* Patients will receive 60 mg daily and then 180 daily in case of progression<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to progression | This study evaluates clinical benefit by comparing sequentially measured paired failure times within each treated patient, namely time to progression after the 60 mg toremifene dose (TTP1) versus the (possibly censored) time to progression after the 180 mg toremifene dose (TTP2) | 2 years |