Study of Continuous Dosing of Sunitinib in Non GIST Sarcomas With Concomitant Radiotherapy

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Centre Leon Berard
Sponsor:
Collaborator:
Ministry of Health, France
Information provided by (Responsible Party):
Centre Leon Berard
ClinicalTrials.gov Identifier:
NCT01308034
First received: March 1, 2011
Last updated: February 24, 2014
Last verified: February 2014
  Purpose

The purpose of this study is to determine the safety of continuous dosing of sunitinib in association with radiotherapy in patients with non GIST (gastro intestinal stromal tumor) sarcomas who cannot be treated by surgery.

The primary objective of the study is to determine the maximum tolerated dose (MTD) of continuous dosing of sunitinib in association with radiotherapy in patients with non GIST sarcomas who cannot be treated by surgery.

This study is a multicentre, open-label phase I with dose escalation : 3 dose levels.

3-6 patients will be included at each dose level.3-18 patients will be included in the study.


Condition Intervention Phase
Non GIST Sarcomas
Drug: sunitinib
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of Continuous Dosing of Sunitinib in Non GIST Sarcomas With Concomitant Radiotherapy

Resource links provided by NLM:


Further study details as provided by Centre Leon Berard:

Primary Outcome Measures:
  • the number of DLT occurring at each dose level of sunitinib within 14 weeks after the start of treatment [ Time Frame: within 14 weeks after the start of treatment ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • the number of early toxicities (within 14 weeks after the beginning of treatment) and late toxicities (after 14 weeks and until 12 months after the start of treatment) using NCI-CTC v3.0 and RTOG-EORTC [ Time Frame: within 12 months after the start of treatment ] [ Designated as safety issue: Yes ]
  • response rate at 6 months using MRI (magnetic resonance imaging) [ Time Frame: 6 months after the start of treatment ] [ Designated as safety issue: No ]
  • progression free survival measured from the date of inclusion to the date of first evidence of progression or date of death of any cause, or to the date of last follow up [ Time Frame: within 12 months after the start of treatment ] [ Designated as safety issue: No ]
  • evolution of neo-angiogenesis during treatment measured by DCE-US [ Time Frame: within 6 weeks after the start of treatment ] [ Designated as safety issue: No ]
  • correlation between clinical response and change of tumor perfusion measured by DCE-US [ Time Frame: within 12 months after the start of treatment ] [ Designated as safety issue: No ]
  • proportion of patients operable after treatment [ Time Frame: at week 6 after the start of treatment ] [ Designated as safety issue: No ]

Estimated Enrollment: 18
Study Start Date: March 2011
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: association sunitinib radiotherapy Drug: sunitinib

All patients will be treated with sunitinib (3 dose level) once a day (in the morning) for 6 weeks in association with radiotherapy.Radiotherapy will be realised 1-4h after taking sunitinib.

Dose level 1 : 12.5 mg once daily Dose level 2 : 25 mg once daily Dose level 3 : 50 mg once daily. Authorization to include a patient in the upper step will be given only if the deadline of 14 weeks after the start of treatment of last patient included were strictly respected and depending of number of DLT occuring.


Detailed Description:

Study design : 3 dose levels

Step 1 : 25 mg once daily Step 2 : 37.5 mg once daily Step 3 : 50 mg once daily

3-6 patients will be included at each of the sunitinib dose levels, depending on the number of DLTs (dose limiting toxicity) occurring in 14 weeks after start of treatment

DLT is defined as :

any grade 3 or 4 musculoskeletal or cutaneous toxicity within the field of radiation any other toxicity > or = 4

Secondary objectives are :

  • to evaluate the safety with late toxicities
  • to estimate the response rate at 6 months
  • to estimate the progression free survival
  • to evaluate the proportion of patients with an operable tumour after treatment

Exploratory objectives are :

  • to study evolution during treatment of neo-angiogenesis measured by dynamic contrast enhanced-ultrasonography (DCE-US)
  • to study the correlation between clinical response and changes of tumor perfusion measured by DCE-US
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female patients > 18 years of age
  2. Histologically or cytologically (in case of recurrence) confirmed connective tissue neoplasm, including any of the following subtypes:

    • Liposarcomas
    • Fibrosarcoma, myxofibrosarcoma
    • Undifferentiated pleomorphic sarcoma
    • Leiomyosarcomas
    • Pleomorphic rhabdomyosarcomas only
    • Angiosarcomas
    • Uncertain differentiated tumors: synovial sarcomas, epithelioid sarcomas, alveolar sarcomas, clear cells sarcomas.

    or osteosarcoma diagnosis, chondrosarcoma or chordoma.

  3. Locally advanced or locally recurrent inoperable tumor without previous irradiation [inoperable status must be assessed by staff including a surgeon specialized in sarcoma].
  4. No prior treatment by sunitinib malate
  5. Life expectancy > 6 months
  6. ECOG performance status ≤ 2
  7. Blood tests, renal and liver functions in the normal range with, in the 7 days prior to study entry, blood or serum values as follows:

    • Absolute neutrophil count ≥ 1.,5 G/L
    • Platelet count ≥ 100 G/L
    • Bilirubin ≤ 1.5 mg/dL
    • PT and INR ≤ 1.5 times upper limit of normal [Patients under preventive anticoagulant therapy are allowed to participate]
    • AST and ALT ≤ 2.5 times upper limit of normal
    • Creatinine ≤ 150 umol/L
    • Calcium ≤ 12 mg/dL
    • Blood glucose < 150 mg/dL
  8. Fertile patients must use effective contraception prior to, during, and for 28 days after completion of study therapy
  9. Ability to swallow oral medications
  10. Mandatory affiliation with a health insurance company
  11. Signed written informed consent.

Exclusion Criteria:

  1. GIST, Ewing sarcoma or embryonic rhabdomyosarcomas
  2. Radiation field including lung, bowel, or central nervous system
  3. Pre-existing thyroid abnormality, defined as abnormal thyroid function tests despite medication
  4. NCI grade ≥ 3 hemorrhage within the past 4 weeks prior to study drug administration
  5. Significant cardiovascular disease (New York Heart Association (NYHA) > grade 2 congestive cardiac failure, myocardial infarction within 6 months prior to inclusion, unstable angina, severe cardiac arrhythmia, severe cerebrovascular accident within 6 months prior to inclusion, history of severe thromboembolism (pulmonary embolism or deep vein thrombosis DVT) within 6 months prior to inclusion (patients with recent history of DVT treated by anticoagulant (except therapeutic warfarin)during at least 6 weeks are eligibles), prolonged QTc interval (QTc > 480 msec with Bazett), bradycardia (heart rate < 45bpm), electrolytic troubles (hyponatremia<120mmol/l, kalemia≥6mmol/l) or uncontrolled hypertension while receiving appropriate medication (≥ 160 mm Hg systolic and/or ≥ 90 mm Hg diastolic).
  6. Less than 6 weeks between prior neoplastic treatment by tyrosine kinase inhibitor and inclusion and less than 4 weeks for other neoplastic treatments
  7. Major surgical procedure, open biopsy, or serious non healing wound within 28 days prior to first day of treatment
  8. Concurrent participation in another clinical trial
  9. Other disease or illness within the past 6 months prior to study drug administration, including the following:

    • Psychiatric illness or social situation that would preclude study compliance
    • Known human immunodeficiency virus (HIV)- or acquired immunodeficiency syndrome (AIDS)-related illness or other active infection
  10. Known brain metastases, spinal cord compression, or carcinomatous meningitis, or evidence of symptomatic brain or leptomeningeal disease
  11. peritoneal carcinosis
  12. number of metastatic sites > 2
  13. Restriction of freedom by judicial or administrative decision
  14. Pregnant or lactating women
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01308034

Contacts
Contact: Ellen Blanc + 33 478 78 29 67 blanc@lyon.fnclcc.fr

Locations
France
Institut Bergonié Recruiting
Bordeaux, France
Contact: Guy Kantor, PR    +33 556 33 33 44      
Principal Investigator: Guy Kantor         
Centre Oscar Lambret Recruiting
Lille, France
Contact: Philippe Nickers, PR    +33 320 29 59 11    p-nickers@o-lambret.fr   
Principal Investigator: Philippe Nickers         
Sub-Investigator: Eric Lartigau         
Sub-Investigator: Nicolas PENEL         
Sub-Investigator: Fabienne WATELLE         
Centre Léon Bérard Recruiting
Lyon, France, 69373
Contact: Jean Yves Blay    +33 478 78 27 57    jean-yves.blay@lyon.unicancer.fr   
Principal Investigator: Jean Yves Blay         
Principal Investigator: Marie Pierre Sunyach         
Sub-Investigator: Philippe CASSIER         
Sub-Investigator: Pierre HEUDEL         
CHU La Timone Not yet recruiting
Marseille, France
Contact: Florence Duffaud, PR    +33 491 38 74 14    fduffaud@mail.ap-hm.fr   
Principal Investigator: Florence Duffaud         
Sub-Investigator: Laetitia PADOVANI         
Sub-Investigator: Delphine Badinand         
Sub-Investigator: Thomas DUBERGE         
Institut de Cancérologie de l'ouest Not yet recruiting
Saint Herblain, France
Contact: Marc MAHE       Marc-Andre.Mahe@ico.unicancer.fr   
Principal Investigator: Marc MAHE         
Sub-Investigator: Emmanuelle BOMPAS         
Institut Gustave Roussy Not yet recruiting
Villejuif, France
Contact: Cécile Le Pechoux    +33 142 11 47 57    cecile.lepechoux@igr.fr   
Principal Investigator: Cécile Le Pechoux         
Sub-Investigator: Axel Le Cesne         
Sub-Investigator: Julien Domont         
Sub-Investigator: Aurore Blesius         
Sub-Investigator: Angela Cioffi         
Sponsors and Collaborators
Centre Leon Berard
Ministry of Health, France
Investigators
Principal Investigator: Jean Yves Blay, PR Centre Léon Bérard, Lyon
Principal Investigator: Marie Pierre Sunyach Centre Léon Bérard, Lyon
  More Information

Publications:

Responsible Party: Centre Leon Berard
ClinicalTrials.gov Identifier: NCT01308034     History of Changes
Other Study ID Numbers: RT - SUTENT, 2010-021551-11
Study First Received: March 1, 2011
Last Updated: February 24, 2014
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Centre Leon Berard:
non GIST sarcomas
sunitinib
radiotherapy
dose escalation

Additional relevant MeSH terms:
Sarcoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Connective and Soft Tissue
Sunitinib
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antineoplastic Agents
Growth Inhibitors
Growth Substances
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014