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Study to Assess Various Sunitinib Schedules in Renal Cell Carcinoma

Phase 2
Conditions
Metastatic Renal Cell Cancer
Kidney Neoplasms
Interventions
Registration Number
NCT02689167
Lead Sponsor
Centre Hospitalier Universitaire de Besancon
Brief Summary

Patients who are candidates for first line treatment with Sunitinib 50mg 4/6 regimen in accordance with the Marketing Authorisation who meet the inclusion/exclusion criteria will be offered participation in this study during the consultation as part of their usual care. The patients will be included before Sunitinib treatment is started. Thereafter, sunitinib is initiated 50 mg/day; regimen 4/6 (Marketing Authorisation Indication), 4 weeks "on " alternating with 2 weeks "off "

As soon as a dose or schedule adjustment is required, regardless of cause, the patient will be randomised 1/1:

* Either into arm A and will receive 37.5mg of Sunitinib per day by the 4/6 regimen (in accordance with the Marketing Authorisation); 4 weeks "on " alternating with 2 weeks "off "

* Or into arm B and will receive 50mg of Sunitinib per day by the 2/3 regimen (investigational arm); 2 weeks "on " alternating with 1 week "off "

Detailed Description

Not available

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
226
Inclusion Criteria
  • Men or women over 18 years old

  • Patients with local, advanced or inoperable or metastatic (MRCC) renal cell carcinoma who are starting first line treatment with Sunitinib 50mg (4/6 regimen) according to the Marketing Authorisation Indication

  • Patients with histologically or cytologically confirmed renal cancer, clear cell variant or with a clear cell component

  • Karnofsky performance status ≥ 70%

  • Adequate organ function:

    • Absolute neutrophil (N) count ≥ 1 500 / µL
    • Platelets ≥ 100 000 / µL
    • Haemoglobin ≥ 10 g/dL
    • Adjusted serum calcium ≤ 2.6 mmol/L
    • Creatinine clearance ≥ 30 mL/min (by the MDRD formula)
    • Total bilirubin ≤ 1.5 x ULN (upper limit of the normal range)
    • AST ≤ 2.5 x ULN and ALT ≤ 2.5 x ULN OR AST and ALT ≤ 5 x ULN if liver abnormalities due to liver metastases AST = aspartate aminotransferase ALT = alanine aminotransferase

Key

Exclusion Criteria
  • Renal carcinoma with no clear cell component.
  • Previous systemic treatment for the RCC regardless of type (including targeted therapy, immunotherapy, chemotherapy, hormone or experimental therapy). Previous or concomitant treatment with a bisphosphonate or denosumab is allowed.
  • Patients whose clinical state and comorbidities are not consistent with administration of Sunitinib at the initial dose of 50mg/day 4 weeks out of 6.
  • Grade 3 haemorrhage within 4 weeks before starting treatment with Sunitinib (according to the NCI-CTCAE toxicity score version 3.0).
  • The presence of a past history of cancer in the 3 years before inclusion into the study
  • Major surgery within 4 weeks before sunitinib initiation
  • Past history of symptomatic cerebral metastases, spinal cord compression or meningeal carcinomatosis. Patients with cerebral metastases discovered incidentally on imaging and who are asymptomatic are not excluded if these metastases have been treated (radiotherapy and/or surgery) with a period of at least 4 weeks between the end of treatment and inclusion into the study and no clinical or radiological signs of relapse, and corticosteroid dose is not exceeding 10mg/day of prednisone or equivalent. Subjects will be excluded if subjects have signs of grade ≥ 2 treatment-related complications.
  • Any of the following features within 6 months of the administration of Sunitinib: myocardial infarction, severe/unstable angina, coronary artery/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack.
  • Pulmonary embolism or deep vein thrombosis within 3 months of inclusion (unless it's stable, asymptomatic and treated with a low molecular weight heparin for at least 6 weeks before inclusion).
  • Any known acute or chronic disorder (such as severe chronic obstructive pulmonary disease) which in the opinion of the investigator could impact on the patient's capacity to receive the study treatment or make interpretation of toxicity or adverse events difficult.
  • Known HIV infection.
  • History of chronic active hepatitis including subjects who are carriers of the hepatitis B (HBV) or hepatitis C (HCV) virus.
  • Existence of uncontrolled infection.
  • Uncontrolled hypertension defined as a blood pressure of > 150 mmHg systolic or > 100 mmHg diastolic despite optimal anti-hypertensive therapy (blood pressure must be controlled at inclusion).

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Arm A 4/6SunitinibSunitinib 37.5 mg/day; regimen 4/6 (Marketing Authorisation Indication) 4 weeks "on " alternating with 2 weeks "off "
Arm B 2/3SunitinibSunitinib 50 mg/day; regimen 2/3 (experimental arm) 2 weeks "on " alternating with 1 week "off "
Primary Outcome Measures
NameTimeMethod
MDT (median duration of treatment)12 mo

The primary objective of this study is to estimate the median duration of treatment in each treatment group (arm A vs arm B) calculated from sunitinib initiation.

Secondary Outcome Measures
NameTimeMethod
PFS (progression-free survival)12 months

To estimate progression-free survival in patients included in each of the groups and in the overall population included in this study.

duration of sunitinib post randomization12 months

Estimation of the time between date of randomization and sunitinib arrest (for any reason) in the two treatment arms.

time to randomization4 months

To estimate the time to randomization defined as the time between the date of sunitinib initiation and the date of randomization.

OS (overall survival)30 months

To estimate overall survival in patients included in each of the groups and in the overall population included in this study.

ORR (objective response rate)6 months

To measure the objective response rate according to RECIST 1.1 criteria.

QOL (quality of life)24 months

To assess health-related quality of life since sunitinib is started (before randomization, at the time of randomization and after randomization)

Number of participants with treatment-related adverse events as assessed by CTCAE v4.024 months

To assess safety profile before and after randomization.

Trial Locations

Locations (1)

CHU Besancon

🇫🇷

Besancon, Franche-Comté, France

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