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

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).

Inclusion Criteria:

1. 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.
2. Age ≥18 years
3. Histological centrally and molecularly confirmed diagnosis of solitary fibrous tumor (inclusive of the last available tumor sample)
4. 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
5. Measurable or evaluable disease with RECIST
6. Evidence of progression by RECIST during the 6 months before study entry
7. 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.
8. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2
9. Adequate bone marrow function
10. Adequate organ function
11. Cardiac ejection fraction ≥50% as measured by echocardiogram
12. 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.
13. No history of arterial and/or venous thromboembolic event within the previous 12 months.

Exclusion Criteria:

1. Any prior treatment with cytotoxic chemotherapy
2. >1 line of anticancer targeted agents
3. Previous treatment with any other investigational or not investigational agents within 14 days of first day of study drug dosing
4. 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
5. Previous radiotherapy to 25 % of the bone marrow
6. Major surgery within 4 weeks prior to study entry
7. 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
8. Pregnancy or breast feeding
9. 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
10. 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
11. Known history of human immunodeficiency virus infection
12. Active or chronic hepatitis B or C requiring treatment with antiviral therapy
13. 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
14. 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
15. Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation of the study drugs
16. Expected non-compliance to medical regimens