Clinical trial NCT00979966: Study in Non-Clear Cell Renal Carcinoma (Ncc-RCC) Temsirolimus Versus Sunitinib
Official title: Prospective Randomized Phase-II Trial With Temsirolimus Versus Sunitinib in Previously Untreated Patients With Advanced or Metastatic Non-Clear Cell Renal Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non-clear Cell Renal Cell Cancer
Keywords: Locally advanced or metastatic non-clear cell renal cell cancer (ncc-RCC)
Lead sponsor: Central European Society for Anticancer Drug Research
Sponsor class: OTHER
First posted: 2009-09-18
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This will be a prospective, open-label, randomized multicenter phase-II study to evaluate progression free survival (PFS) in patients with locally advanced or metastatic non-clear cell renal cell cancer (ncc-RCC) receiving Temsirolimus in comparison to Sunitinib.

In most clinical trials in renal cell carcinoma (RCC), clear cell RCC have been included exclusively. There are only some limited data on the efficacy of Temsirolimus or Sunitinib in ncc-RCC showing interesting response rates for both agents. However, randomized clinical trials in this specific patient population have not yet been performed.

In the proposed study a comparison Temsirolimus and Sunitinib is scheduled in first line therapy of ncc-RCC.


Eligibility criteria: Inclusion Criteria:

1. Adult males and females: ≥18 years of age.
2. Locally advanced or metastatic, histological confirmed, non-clear cell RCC of all subtypes. Patients must have advanced non-clear cell of one of the following subtypes: papillary, chromophobe, collecting duct carcinoma (CDC), renal medullary carcinoma (RMC), or unclassified.
3. Patients with measurable disease (at least one uni-dimensionally measurable target lesion by CT-scan or MRI) according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) If prior palliative radiotherapy to metastatic lesions: ≥ 1 measurable lesion that has not been irradiated.
4. PS 0-2 ECOG
5. Signed written informed consent.
6. White blood cell count (WBC) ≥4x10\*9/L with neutrophils ≥1.5 x 10\*9/L, platelet count ≥100x10\*9/L, hemoglobin ≥9 g/dL.\]
7. Total bilirubin \<2 x upper limit of normal.
8. AST and ALT \<2.5 x upper limit of normal, or \<5 x upper limit of normal in case of liver metastases.
9. Serum creatinine \<2.0 x upper limit of normal.
10. Normal ECG without QT prolongation (QTc \< 450msec).
11. Adequate cardiac function (left ventricular ejection fraction \> 40% as assessed by ECHO.

Exclusion Criteria:

1. Predominant clear-cell RCC
2. Resectability or other curative options
3. Any investigational drug within the 30 days before inclusion.
4. Prior systemic treatment for their RCC.
5. Known or suspected allergy or hypersensitivity reaction to any of the components of study treatments.
6. Radiotherapy within the last 4 weeks.
7. Pregnancy (absence to be confirmed by beta-hCG test) or lactation period.
8. Men or women of child-bearing potential who are sexually active and unwilling to use a medically acceptable method of contraception during the trial.
9. Clinically symptomatic brain or meningeal metastasis. (known or suspected)
10. Cardiac arrhythmias requiring anti-arrhythmics (excluding beta blockers or digoxin).
11. History of any of the following cardiac events within the past 6 months:

    * myocardial infarction (including severe/unstable angina),
    * coronary/peripheral artery bypass graft,
    * congestive heart failure (CHF),
    * cerebrovascular accident,
    * transient ischemic attack,
    * pulmonary embolism.
12. No hemorrhage ≥ grade 3 within the past 4 weeks
13. Uncontrolled severe hypertension (failure of diastolic blood pressure to fall below 90 mm Hg despite the use of ≥3 anti-hypertensive drugs
14. History of relevant pulmonary hypertension or interstitial lung disease.
15. Acute or sub-acute intestinal occlusion or history of inflammatory bowel disease or chronic diarrhea
16. Previous malignancy (other than renal cancer cancer) in the last 5 years except basal cell cancer of the skin, pre-invasive cancer of the cervix or superficial bladder tumor \[Ta, Tis and T1\].
17. History of organ allograft
18. Significant disease which, in the investigator's opinion would exclude the patient from the study
19. Patients with seizure and epileptic disorder or other conditions requiring medication (such as phenytoin, carbamazepin, phenobarbital)
20. Patients under strong inducers or inhibitors to CYP Isoenzymes
21. Patients with hypersensitivity to the antihistamine or patients who cannot receive the antihistamine for other medical reasons
22. Patients requiring long-term cortisone therapy
23. Patients requiring oral anticoagulation treatment, such as marcoumar. (Anticoagulation treatment with heparin or low molecular weight heparin \[LMWH\] is allowed provided that close monitoring is performed).
24. Surgery within at least 2 weeks prior to randomization
25. HIV seropositivity.
26. Abnormal pulmonary function (DLCO \< 50%). \[Pulmonary function tests need only to be performed if abnormal pulmonary function present in medical history\].
27. Poorly controlled diabetes mellitus.
28. Liver cirrhosis, chronic hepatitis
29. Legal incapacity or limited legal capacity
30. Known alcohol or drug abuse.
31. Medical or psychological conditions that would not permit the patient to complete the study or sign informed consent.

Primary outcomes:
measure: Time to progression
timeFrame: 7-11 months expected
Secondary outcomes:
measure: Objective response
timeFrame: 7-11 months expected
measure: safety assessed using CTCAE v3.0 and safety assessed according to reported SAEs
timeFrame: 8-12 months (treatment duration + 1 months)
measure: one year progression free survival rate (1YPFSR)
timeFrame: 1 year
measure: overall survival (OS)
timeFrame: will be evaluated in 2013
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Charité - Campus Virchow Klinikum
city: Berlin
country: Germany
facility: Charité - Mitte
city: Berlin
country: Germany
facility: Vivantes Klinikum am Urban
city: Bonn
country: Germany
facility: Evangelische Kliniken Bonn gGmbH - Johanniter-Krankenhaus
city: Düsseldorf
country: Germany
facility: Universitätsklinikum Düsseldorf
city: Essen
country: Germany
facility: Universitätsklinikum Essen
city: Frankfurt
country: Germany
facility: Klinikum der J.W. Goethe Universität
city: Halle
country: Germany
facility: Martin-Luther-Universität Halle-Wittenberg
city: Jena
country: Germany
facility: Universitätskrankenhaus Jena
city: Lübeck
country: Germany
facility: UK-SH Campus Lübeck
city: Oldenburg
country: Germany
facility: Klinikum Oldenburg gGmbH
city: Stuttgart
country: Germany
facility: Klinikum Stuttgart, Katharinenhospital
city: Viersen
country: Germany
facility: Facharzt für Innere Medizin,
city: Weiden
country: Germany
facility: Kliniken Nordoberpfalz AG - Klinikum Weiden
Study officials:
References: