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

Primary Purpose

Desmoid Type-fibromatosis

Status

Unknown status

Phase

Phase 2

Locations

Italy

Study Type

Interventional

Intervention

Toremifene

About this trial

This is an interventional treatment trial for Desmoid Type-fibromatosis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Fondazione IRCCS Istituto Tumori MilanoRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Toremifene treatment

Arm Description

Patients will receive 60 mg daily of Toremifene and the dose will be escalated to 180 mg daily in case of progression

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

Full Information

NCT ID

NCT02353429

First Posted

January 28, 2015

Last Updated

January 30, 2015

Sponsor

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Collaborators

Associazione Italiana per la Ricerca sul Cancro

1. Study Identification

Unique Protocol Identification Number

NCT02353429

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2015

Overall Recruitment Status

Unknown status

Study Start Date

November 2012 (undefined)

Primary Completion Date

June 2015 (Anticipated)

Study Completion Date

December 2015 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Collaborators

Associazione Italiana per la Ricerca sul Cancro

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

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

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Desmoid Type-fibromatosis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

25 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Toremifene treatment

Arm Type

Experimental

Arm Description

Patients will receive 60 mg daily of Toremifene and the dose will be escalated to 180 mg daily in case of progression

Intervention Type

Drug

Intervention Name(s)

Toremifene

Intervention Description

Patients will receive 60 mg daily and then 180 daily in case of progression

Primary Outcome Measure Information:

Title

Time to progression

Description

Time Frame

2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Chiara Colombo, MD

Phone

+39022390

Ext

3234

chiara.colombo@istitutotumori.mi.it

First Name & Middle Initial & Last Name or Official Title & Degree

Lorella Rusi, MD

Phone

+39022390

Ext

3714

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Chiara Colombo, MD

Organizational Affiliation

Fondazione IRCCS Istituto Tumori Milano

Official's Role

Principal Investigator

Facility Information:

Facility Name

Fondazione IRCCS Istituto Tumori Milano

City

Milan

ZIP/Postal Code

20133

Country

Italy

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Chiara Colombo, MD

Phone

+39023903234

chiara.colombo@istitutotumori.mi.it

12. IPD Sharing Statement

Citations:

PubMed Identifier

26602014

Citation

Fiore M, Colombo C, Radaelli S, Callegaro D, Palassini E, Barisella M, Morosi C, Baldi GG, Stacchiotti S, Casali PG, Gronchi A. Hormonal manipulation with toremifene in sporadic desmoid-type fibromatosis. Eur J Cancer. 2015 Dec;51(18):2800-7. doi: 10.1016/j.ejca.2015.08.026. Epub 2015 Nov 18.

Results Reference

derived

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

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