Clinical trial NCT02587169: Trial of Nilotinib and Adriamycin as Treatment in Liposarcomas and Leiomyosarcomas of Retroperitoneum
Official title: GEIS-27: Phase I/II Multicenter and Prospective Trial of Nilotinib and Adriamycin as Neoadjuvant Treatment in Liposarcomas and Leiomyosarcomas of Retroperitoneum
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Retroperitoneal Liposarcoma
Retroperitoneal Leiomyosarcoma
Chondrosarcoma
Keywords: liposarcoma
leiomyosarcoma
retroperitoneum
chondrosarcoma
Lead sponsor: Broto, Javier Martín, M.D.
Sponsor class: INDIV
First posted: 2015-10-27
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Relapse-free survival (RFS) at 5 years
timeFrame: 5 years
Secondary outcomes:
measure: Objective response rate (ORR) (confirmed complete response [CR] and partial response [PR])
timeFrame: Baseline and at 4 months
measure: Overall survival (OS)
timeFrame: 100 months
measure: Number of adverse events
timeFrame: 4 months
Other outcomes:
Locations:
city: Palma de Mallorca
country: Spain
facility: Hospital Universitari Son Espases
state: Balearic Islands
city: Badajoz
country: Spain
facility: Hospital Infanta Cristina
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trials i Pujol
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Castellón
country: Spain
facility: Hospital Provincial de Castellón
city: La Laguna
country: Spain
facility: Hospital Universitario de Canarias
city: León
country: Spain
facility: Complejo Asistencial Universitario de León
city: Madrid
country: Spain
facility: Hospital Puerta de Hierro
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Murcia
country: Spain
facility: Hospital Universitario Virgen de la Arrixaca
city: Pamplona
country: Spain
facility: Complejo Hospitalario de Navarra
city: Santander
country: Spain
facility: Hospital Marqués de Valdecilla
city: Santiago de Compostela
country: Spain
facility: Hospital Clínico Universitario de Santiago
city: Sevilla
country: Spain
facility: Hospital Virgen del Rocío
city: Toledo
country: Spain
facility: Hospital Virgen de la Salud
city: Valencia
country: Spain
facility: Instituto Valenciano de Oncología
city: Vigo
country: Spain
facility: Hospital Xeral Cies
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
Study officials:
affiliation: Spanish Sarcoma Group (GEIS)
name: Javier Martín, MD, PhD
role: STUDY_DIRECTOR
References: