Trial of Nilotinib and Adriamycin as Treatment in Liposarcomas and Leiomyosarcomas of Retroperitoneum (GEIS-27)

October 23, 2015 updated by: Broto, Javier Martín, M.D.

GEIS-27: Phase I/II Multicenter and Prospective Trial of Nilotinib and Adriamycin as Neoadjuvant Treatment in Liposarcomas and Leiomyosarcomas of Retroperitoneum

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

40

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Spain
      • Badajoz, Spain
        • Recruiting
        • Hospital Infanta Cristina
        • Contact:
        • Principal Investigator:
          • Ignacio Delgado, MD
      • Badalona, Spain
        • Recruiting
        • Hospital Universitari Germans Trials i Pujol
        • Contact:
        • Principal Investigator:
          • Olatz Etxaniz, MD
      • Barcelona, Spain
        • Recruiting
        • Hospital Universitari Vall d'Hebron
        • Principal Investigator:
          • Claudia Valverde, MD
        • Contact:
      • Barcelona, Spain
        • Recruiting
        • Hospital de La Santa Creu I Sant Pau
        • Contact:
        • Principal Investigator:
          • Antonio López-Pousa, MD
      • Castellón, Spain
        • Recruiting
        • Hospital Provincial de Castellón
        • Principal Investigator:
          • Ramón de las Peñas, MD
        • Contact:
      • La Laguna, Spain
      • León, Spain
        • Recruiting
        • Complejo Asistencial Universitario de León
        • Contact:
        • Principal Investigator:
          • Luis Miguel de Sande, MD
      • Madrid, Spain
        • Recruiting
        • Hospital Universitario La Paz
        • Contact:
        • Principal Investigator:
          • Andrés Redondo, MD
      • Madrid, Spain
        • Recruiting
        • Hospital Universitario Ramon Y Cajal
        • Contact:
        • Principal Investigator:
          • Mª Ángeles Vaz, MD
      • Madrid, Spain
        • Recruiting
        • Hospital Puerta de Hierro
        • Contact:
        • Principal Investigator:
          • Ricardo Cubedo, MD
      • Murcia, Spain
        • Recruiting
        • Hospital Universitario Virgen de la Arrixaca
        • Contact:
      • Pamplona, Spain
      • Santander, Spain
        • Recruiting
        • Hospital Marques de Valdecilla
        • Contact:
        • Principal Investigator:
          • Ana de Juan, MD
      • Santiago de Compostela, Spain
        • Recruiting
        • Hospital Clinico Universitario de Santiago
        • Contact:
        • Principal Investigator:
          • Yolanda Vidal, MD
      • Sevilla, Spain
        • Recruiting
        • Hospital Virgen Del Rocio
        • Contact:
        • Principal Investigator:
          • Pilar Sancho, MD
      • Toledo, Spain
        • Recruiting
        • Hospital Virgen De La Salud
        • Contact:
        • Principal Investigator:
          • Javier Medina, MD
      • Valencia, Spain
        • Recruiting
        • Instituto Valenciano de Oncologia
        • Contact:
        • Principal Investigator:
          • Javier Lavernia, MD
      • Vigo, Spain
      • Zaragoza, Spain
        • Recruiting
        • Hospital Universitario Miguel Servet
        • Contact:
        • Principal Investigator:
          • Javier Martínez-Trufero, MD
    • Balearic Islands
      • Palma de Mallorca, Balearic Islands, Spain
        • Recruiting
        • Hospital Universitari Son Espases
        • Contact:
        • Principal Investigator:
          • Javier Martín, MD, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 68 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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).
Drug: 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).
Other Names:
  • Nilotinib Tasigna
  • Doxorubicin hydrochloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Relapse-free survival (RFS) at 5 years
Time Frame: 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.
5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective response rate (ORR) (confirmed complete response [CR] and partial response [PR])
Time Frame: 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
Baseline and at 4 months
Overall survival (OS)
Time Frame: 100 months
Overall survival measured from treatment start date until date of death, whichever the cause, assessed up to 100 months
100 months
Number of adverse events
Time Frame: 4 months
Number and type of adverse events according to CTCAE 4.0
4 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Broto, Javier Martín, M.D.

Investigators

  • Study Director: Javier Martín, MD, PhD, Spanish Sarcoma Group (GEIS)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2012

Primary Completion (Anticipated)

December 1, 2015

Study Completion (Anticipated)

December 1, 2015

Study Registration Dates

First Submitted

July 17, 2013

First Submitted That Met QC Criteria

October 23, 2015

First Posted (Estimate)

October 27, 2015

Study Record Updates

Last Update Posted (Estimate)

October 27, 2015

Last Update Submitted That Met QC Criteria

October 23, 2015

Last Verified

October 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EC10-150 RETRONEO
  • 2011-002368-26 (EudraCT Number)
  • GEIS-27 (Other Identifier: Spanish Sarcoma Group (GEIS))

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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