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

January 3, 2022 updated by: Centre Leon Berard

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

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 : 2 dose levels.

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Study design : 2 dose levels

Step 1 : 25 mg once daily Step 2 : 37.5 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

Study Type

Interventional

Enrollment (Actual)

25

Phase

  • 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 Locations

  • France
      • Bordeaux, France
        • Institut Bergonié
      • Lille, France
        • Centre Oscar Lambret
      • Lyon, France, 69373
        • Centre Leon Berard
      • Marseille, France
        • CHU La Timone
      • Saint Herblain, France
        • Institut de Cancérologie de l'Ouest
      • Villejuif, France
        • Institut Gustave Roussy

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

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

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: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: association sunitinib radiotherapy
Drug: sunitinib

All patients will be treated with sunitinib (2 dose levels) 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 : 25 mg once daily Dose level 2 : 37.5 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
within 14 weeks after the start of treatment

Secondary Outcome Measures

Outcome Measure
Time Frame
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
within 12 months after the start of treatment
response rate at 6 months using MRI (magnetic resonance imaging)
Time Frame: 6 months after the start of treatment
6 months after the start of treatment
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
within 12 months after the start of treatment
evolution of neo-angiogenesis during treatment measured by DCE-US
Time Frame: within 6 weeks after the start of treatment
within 6 weeks after the start of treatment
correlation between clinical response and change of tumor perfusion measured by DCE-US
Time Frame: within 12 months after the start of treatment
within 12 months after the start of treatment
proportion of patients operable after treatment
Time Frame: at week 6 after the start of treatment
at week 6 after the start of treatment

Collaborators and Investigators

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

Sponsor

Centre Leon Berard

Collaborators

Ministry of Health, France

Investigators

  • Principal Investigator: Marie Pierre Sunyach, Centre Leon Berard, Lyon

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.

General Publications

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

March 1, 2011

Primary Completion (ACTUAL)

May 1, 2016

Study Completion (ACTUAL)

September 21, 2016

Study Registration Dates

First Submitted

March 1, 2011

First Submitted That Met QC Criteria

March 2, 2011

First Posted (ESTIMATE)

March 3, 2011

Study Record Updates

Last Update Posted (ACTUAL)

January 18, 2022

Last Update Submitted That Met QC Criteria

January 3, 2022

Last Verified

January 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RT - SUTENT
  • 2010-021551-11 (EUDRACT_NUMBER)

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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