Trial assessing the activity of TrabectedIn vs gemCitabine in patients with advanced LEiomyosarcoma

Phase 1

• Conditions: metastatic or locally advanced Leiomyosarcoma pretreated with conventional chemotherapy; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2020-000741-13-IT
• Lead Sponsor: ITALIAN SARCOMA GROUP

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-06-08
• Last Update Posted: 30 August 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

1.Patients with histologically documented diagnosis of leiomyosarcoma and not surgically resectable or metastatic leiomyosarcoma that progressed after first- or further-line treatments for relapsing disease.
2.Patients with diagnosis of unresectable or metastatic leiomyosarcoma
3.Patients who received at least on previous systemic treatment with Anthracycline-based chemotherapy.
4.Patients suitable to receive gemcitabine or trabectedin therapy (for the randomized cohort only)
5.Measurable or evaluable disease with RECIST 1.1 criteria.
6.Evidence of progression according RECIST 1.1 during the 6 months before study entry.
7.Age =18 years
8.Eastern Cooperative Oncology Group (ECOG) Performance Status = 2
9.All previous anticancer treatments must have completed = 3 weeks (21 days) prior to first dose of study drug.
10. The patient has resolution of adverse events, with the exception of alopecia, and of all clinically significant toxic effects of prior loco-regional therapy, surgery, radiotherapy or systemic anticancer therapy to = Grade 1, by National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0
11.Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted at screening and repeated within 7 days prior to start of treatment:
12.Left Ventricular Ejection Fraction = 50% and/or above lower institutional limit of normality.
13.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 amenorhoic 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 during the trial and up to 3 months following the last dose of study treatment.
14.No history of arterial and/or venous thromboembolic event within the previous 12 months.
15.The patient or legal representative must be able to read and understand the informed consent form and must have been willing to give written informed consent prior to any study specific procedure. The subject may also provide an optional consent for the biological/translational sub-study associated. However, the subject may participate in the main trial without participating in biological/translational

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 60
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 40

Exclusion Criteria

1.Prior treatment with Trabectedin and/or Gemcitabine (for the randomized cohort only)
2.Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation of the study drugs
3.History of other malignancies (except basal cell carcinoma or cervical carcinoma in situ, adequately treated), unless in remission from 5 years or more and judged of negligible potential of relapse.
4.Persistent toxicities (=CTCAE grade 2) with the exception of alopecia, caused by previous anticancer therapies
5.Metastatic brain or meningeal tumors (unless the patient is > 6 months from definitive therapy, does not require corticosteroid treatment, has a negative imaging study within 4 weeks of study entry and is clinically stable with respect to the tumor at the time of study entry).
6.Active viral hepatitis (HBV or HCV infection). Active hepatitis B virus (HBV) is defined by a known positive HBV surface antigen (HBsAg) result. Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody and absence of HBsAg) are eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
7.Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV).
8.Patients with any severe and/or uncontrolled medical conditions such as unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction = 6 months, serious uncontrolled cardiac arrhythmia, uncontrolled hyperlipidemia, cirrhosis, chronic or persistent active hepatitis or severely impaired lung function. In particular for history of cardiac disease: congestive heart failure = NYHA class 2; active coronary artery disease (myocardial infarction more than 6 months prior to study entry is allowed); cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted) or uncontrolled hypertension, unstable spinal cord compression (untreated and unstable for at least 28 days prior to study entry), superior vena cava syndrome, extensive bilateral lung disease on High Resolution CT scan.
9.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
10.Active clinically serious infections (> grade 2 NCI-CTC version 5.0).
11.Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV).
12.Previous treatment with radiation therapy within 14 days of first day of study drug dosing,
13.Major surgery within 4 weeks prior to study entry
14.Concomitant use of known strong CYP3A inhibitors (eg. Ketoconazole, itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (eg. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil).
15.Concomitant use of known strong (eg. phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John’s Wort ) or moderate CYP3A inducers (eg. bosentan, efavirenz, modafinil).
16.Patients undergoing renal dialysis or with ClCr <30 ml/min or Creatinine >1,5 mg/dL
17.Pregnant or breast feeding patients
18.Patients with severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could caus

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified