Study With Trabectedin Versus Adriamycin Plus Dacarbazine, in Patients With Advanced Solitary Fibrous Tumor

Study Overview
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Brief Summary
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Phase II randomized study for the comparison of trabectedin versus doxorubicin plus dacarbazine in patients with advanced solitary fibrous tumor

Detailed Description
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Patients with solitary fibrous tumor will be randomized to receive 6 cycles of trabectedin or doxorubicin plus dacarbazine. In case of progression or unacceptable toxicity while under the experimental treatment prior to the completion of the 6 cycles, the patients will be offered to cross to the other arm (trabectedin arm to doxorubicin plus dacarbazine arm and vice versa).

Official Title
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Solitary Fibrous Tumor: Phase II Study on Trabectedin Versus Adriamycin Plus Dacarbazine in Advanced Patients

Conditions
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Solitary Fibrous Tumors

Intervention / Treatment
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* Drug: Trabectedin
* Drug: Adriamycin
* Drug: Dacarbazine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patient or legal representative must be able to read and understand the informed consent form (ICF) and must have been willing to give written informed consent and any locally required authorisation before any study-specific procedures, including screening evaluations, sampling, and analyses. Age ≥18 years Histological centrally and molecularly confirmed diagnosis of solitary fibrous tumor (inclusive of the last available tumor sample) Locally advanced disease (i.e. surgical resection of local disease unfeasible radically, or unaccepted by the patient, or amenable to become less demolitive, or feasible, or easier, after cytoreduction) and/or metastatic disease Measurable or evaluable disease with RECIST Evidence of progression by RECIST during the 6 months before study entry Patients must be cytotoxic chemotherapy naïve (patients treated with neoadjuvant/adjuvant chemotherapy cannot be included) or could have received a previous target agent in front-line setting. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2 Adequate bone marrow function Adequate organ function Cardiac ejection fraction ≥50% as measured by echocardiogram Female patients of child-bearing potential must have negative pregnancy test within 7 days before initiation each cycle of chemotherapy. Post-menopausal women must be amenorrhoeic 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 method of birth control throughout the study. No history of arterial and/or venous thromboembolic event within the previous 12 months. Exclusion Criteria: Any prior treatment with cytotoxic chemotherapy >1 line of anticancer targeted agents Previous treatment with any other investigational or not investigational agents within 14 days of first day of study drug dosing Previous treatment with radiation therapy within 14 days of first day of study drug dosing, or patients who have not recovered from adverse events due to agents previously administered Previous radiotherapy to 25 % of the bone marrow Major surgery within 4 weeks prior to study entry Other primary malignancy with <5 years clinically assessed disease-free interval, except basal cell skin cancer, cervical carcinoma in situ, or other neoplasms judged to entail a low risk of relapse Pregnancy or breast feeding Cardiovascular diseases resulting in a New York Heart Association Functional Status >2 (24). Medical history of a myocardial infarction < 6 months prior to initiation of study treatment Medical history of arterial thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), or pulmonary embolism within 6 months prior to the initiation of study treatment Known history of human immunodeficiency virus infection Active or chronic hepatitis B or C requiring treatment with antiviral therapy Medical history of hemorrhage or a bleeding event ≥ Grade 3 (NCI-CTCAE v 4.0) within 4 weeks prior to the initiation of study treatment Evidence of any other serious or unstable illness, or medical, psychological, or social condition, that could jeopardize the safety of the subject and/or his/her compliance with study procedures, or may interfere with the subject's participation in the study or evaluation of the study results Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation of the study drugs Expected non-compliance to medical regimens

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
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Trabectedin<br>trabectedin: 1.5 mg/m² - 1.3 mg/m² given in 24-hour continuous infusion every 21 days for 6 cycles | Drug: Trabectedin<br>* Treatment with trabectedin repeated every 21 days for 6 cycles<br>|
| Experimental: Adriamycin and Dacarbazine<br>Adriamycin: 75 mg/m2/day, bolus, day 1 every 21 days for 6 cycles Dacarbazine: 400 mg/m2/day, days 1, 2 every 21 days for 6 cycles | Drug: Adriamycin<br>* Treatment with Adriamycin at day 1 every 21 days for 6 cycles<br>Drug: Dacarbazine<br>* Treatment with Dacarbazine at days 1 and 2 every 21 days for 6 cycles<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Tumor Response Rate | evaluate the activity of trabectedin and of adriamycin in combination with dacarbazine, according to Response Evaluation Criteria in Solid Tumor (RECIST), version 1.1 | From the date of randomization until the date of first documented progression or date of death from any cause, whichever came first assessed up to 54 weeks. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Choi Response Rate | Percentage of patient who experienced Complete or Partial Responses after treatment according to Choi Criteria. | week 6, week 12, week 18, then every 12 weeks up to 54 weeks | 
| Overall Survival (OS) | Time from the date of enrollment to date of death | From enrollment up to 5 years | 
| Progression Free Survival (PFS) | Survival free of progressive disease evaluated from enrollment up to progression according to RECIST, or death | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 52 weeks | 
| Clinical Benefit Rate (CBR) | Percentage of patients who have achieved complete response, partial response or stable disease ≥ 6 months | week 6, week 12, week 18, then every 12 weeks up to 54 weeks | 
| Response rate by RECIST after the cross over | Percentage of patient who experienced Complete or Partial Responses according RECIST 1.1 after cross over | week 18, week 24, week 30, week 36 and then every 12 weeks up to 54 weeks | 
| Progression Free Survival (PFS) after cross over up to progression according to RECIST, or death | Survival free of progressive disease evaluated from | From date of cross over until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 52 weeks | 
| Safety according to Common Terminology Criteria for Adverse Events (CTCAE) | Safety profile of the treatment evaluated according to Common Terminology Criteria for Adverse Events version 4.03 | From enrollment every 3 weeks up to 54 weeks |