Trial of Nilotinib and Adriamycin as Treatment in Liposarcomas and Leiomyosarcomas of Retroperitoneum
- Conditions
- ChondrosarcomaRetroperitoneal LiposarcomaRetroperitoneal Leiomyosarcoma
- Interventions
- Drug: Nilotinib-adriamycin
- Registration Number
- NCT02587169
- Lead Sponsor
- Broto, Javier Martín, M.D.
- Brief Summary
Phase I/II multicenter and prospective trial of nilotinib and adriamycin as neoadjuvant treatment in liposarcomas and leiomyosarcomas of retroperitoneum.
The main objective of this study is to improve relapse-free survival (RFS)and overall survival (OS) decreasing from 50% to 30% the relapse percentage at 5 years in patients with resected sarcoma of retroperitoneum.
Secondary objectives include the analysis of antitumoral activity through response rate (RECIST and tissular changes), the assessment of positive correlation between biomarkers and clinical results, the study of long term overall survival, and the analysis of the safety profile of the nilotinib-adriamycin combination.
The trial hypothesis is that the nilotinib-adriamycin combination is synergistic and therefore better response results are expected (from 20% as P0 to 40% as P1). The study seeks to find a positive correlation between biomarkers and clinical results in retroperitoneal liposarcoma and leiomyosarcoma treated with the mentioned combination.
The study involves the participation of 20 hospitals of the Spanish Sarcoma Group (GEIS). The treatment consists of 4 neoadjuvant cycles of nilotinib-adriamycin on patients with resectable retroperitoneal sarcoma. The research comprises a robust translational study as well as histological and radiological reviews.
- Detailed Description
The nilotinib-adriamycin combination will be given in 4 cycles of 21 days. In each cycle, nilotinib will be administered at fixed dose of 400 mg/12h orally during 6 consecutive days (1-6) and endovenous adriamycin (20 minutes) on day 5 at three levels (in phase I, dosage of 60 mg/m2, 65 mg/m2, and 75 mg/m2 will be tested to determine the recommended dose for phase II).
Phase I includes patients with retroperitoneal liposarcoma, retroperitoneal leiomyosarcoma and chondrosarcoma. Phase II is focused on retroperitoneal liposarcoma and leiomyosarcoma only.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 40
- Patients with histological diagnosis of well differentiated liposarcoma, dedifferentiated liposarcoma or primary leiomyosarcoma of retroperitoneum and resectable. In phase I the study will recruit patients with high-grade chondrosarcoma of non-mesenchymal type.
- Age: 18-70 years.
- Measurable disease, according to RECIST criteria.
- Functional status: 0-1 (ECOG).
- Baseline medullar function (hemoglobin > 10 g/dL, leukocytes ≥ 3.000/mm3, RAN≥ 1,5 x 109 /l, granulocytes ≥ 1.500/mm3, platelets ≥ 100.000/mm3). Patients with alteration of transaminases ≤ 2.5 times the normal limits, bilirubin total ≤ LSN, CPK≤ 2.5 times the normal limits, alkaline phosphatase ≤ 2.5 times more the normal limits or creatinine values ≤ 1.6 mg/dL, are accepted.
- Cardiac function (LVEF) normal, considering the normal ranges of the institution.
- The patient must voluntarily sign the informed consent before any trial test, knowing that he/she can leave the trial at any time, without any consequence for his/her posterior medical attention.
- Patients in fertile age (both male and female) must use an effective contraceptive method before the entry in the study and during the trial. Moreover, women must maintain contraceptive measures up to 5 months after the treatment. Pregnancy must be ruled out though urine test (negative pregnancy test) for study enrolment.
- Patients having received previous chemotherapy.
- Patient having been irradiated on the tumoral disease.
- Functional status > 1 (ECOG).
- Metastasis in any location.
- Bilirubin values over the normal level. Creatinine over 1.6 mg/dL.
- History of another oncological disease except basalioma or in situ cervical carcinoma adequately treated.
- Serious cardiovascular diseases (dyspnea >= 2 NYHA, ie.)
- Systemic pathologies limiting survival to less than 2 years, limiting patient availability, or those that, by clinical judgement, may interfere significantly with treatment toxicity.
- Bacterial, viral, or uncontrolled mycotic infectious diseases.
- Pregnant or lactating patients.
- Psychological, family, sociological or geographical situations not allowing protocol fulfilment or informed consent signature.
- Patients currently involved in other clinical trials receiving any other agent under investigation.
- Patient having participated in a clinical trial and/or having received an agent under investigation in the 30 days prior to enrolment.
- Patients requiring treatments with prolongation of QT interval as amiodarone, disopyramide, procainamide, quinidine, and sotalol.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Nilotinib-adriamycin Nilotinib-adriamycin The nilotinib-adriamycin combination will be given in 4 cycles of 21 days. In each cycle, nilotinib will be administered at fixed dose of 400 mg/12h orally during 6 consecutive days (1-6) and endovenous adriamycin (20 minutes) on day 5 at three levels (in phase I, dosage of 60 mg/m2, 65 mg/m2, and 75 mg/m2 will be tested to determine the recommended dose for phase II).
- Primary Outcome Measures
Name Time Method Relapse-free survival (RFS) at 5 years 5 years The main goal of the study is to improve relapse-free survival (RFS) and overall survival (OS) decreasing from 50% to 30% the percentage of relapse at 5 years in patients with resected retroperitoneal sarcoma.
- Secondary Outcome Measures
Name Time Method Overall survival (OS) 100 months Overall survival measured from treatment start date until date of death, whichever the cause, assessed up to 100 months
Number of adverse events 4 months Number and type of adverse events according to CTCAE 4.0
Objective response rate (ORR) (confirmed complete response [CR] and partial response [PR]) Baseline and at 4 months To determine the objective response rate (ORR) (confirmed complete response \[CR\] and partial response \[PR\]) using RECIST 1.1 criteria
Trial Locations
- Locations (20)
Hospital Puerta de Hierro
🇪🇸Madrid, Spain
Hospital Universitari Germans Trials i Pujol
🇪🇸Badalona, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Hospital Clínico Universitario de Santiago
🇪🇸Santiago de Compostela, Spain
Hospital Universitario Ramón y Cajal
🇪🇸Madrid, Spain
Hospital Marqués de Valdecilla
🇪🇸Santander, Spain
Hospital Virgen del Rocío
🇪🇸Sevilla, Spain
Hospital Xeral Cies
🇪🇸Vigo, Spain
Hospital Infanta Cristina
🇪🇸Badajoz, Spain
Hospital Universitari Son Espases
🇪🇸Palma de Mallorca, Balearic Islands, Spain
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Complejo Asistencial Universitario de León
🇪🇸León, Spain
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Provincial de Castellón
🇪🇸Castellón, Spain
Complejo Hospitalario de Navarra
🇪🇸Pamplona, Spain
Hospital Virgen de la Salud
🇪🇸Toledo, Spain
Instituto Valenciano de Oncología
🇪🇸Valencia, Spain
Hospital Universitario de Canarias
🇪🇸La Laguna, Spain
Hospital Universitario Miguel Servet
🇪🇸Zaragoza, Spain
Hospital Universitario Virgen de la Arrixaca
🇪🇸Murcia, Spain