Status:

TERMINATED

Trial to Evaluate Paclitaxel Plus RAD001 in Urothelial Carcinoma

Lead Sponsor:

Heinrich-Heine University, Duesseldorf

Conditions:

Bladder Cancer

Eligibility:

All Genders

18+ years

Phase:

PHASE2

Brief Summary

This is a single arm open- label phase II- trial evaluating safety and efficacy of paclitaxel and RAD001 in patients with metastatic urothelial bladder cancer who failed prior platin-based systemic th...

Detailed Description

The screening phase for checking eligibility and evaluation of the patient prior start of study treatment will last up to 21 days.Tumor histology must be predominant urothelial carcinoma and confirmed...

Eligibility Criteria

Inclusion

  • Patients with histologically proven carcinoma of the urinary tract including urinary bladder, ureter, renal pelvis and lower urinary tract. Urothelial carcinoma should be the predominant histology
  • Confirmation of locally relapsed or metastatic disease by imaging. Measurable disease according to RECIST- guidelines with ≥1 measurable lesion has to be evident.
  • If bone is the only metastatic site a quantification of the target lesion(s) using MRI is mandatory.
  • Failure of prior platin- based chemotherapy
  • Patients may have shown progressive disease within the first 3 months of platin-based chemotherapy (primary failure) or progression within 3 months after the end of platin-based chemotherapy (early relapse)-Prior therapy with ≤ 4 chemotherapeutic drugs
  • Patients with tumor relapse within 3 months after cystectomy in the neoadjuvant or adjuvant setting are not eligible.
  • ECOG performance status 0-2
  • Adequate haematological, liver and renal functions.
  • Neutrophil count \> 1500/mm3, haemoglobin \> 9 g/dl, platelets ≥ 100.000/ mm3
  • Serum bilirubin ≤ 1.5 x ULN, ALT and AST ≤ 2.5x ULN. Patients with known liver metastases who have an AST and ALT ≤ 5x ULN.
  • serum creatinine ≤ 2 x ULN.
  • Women of childbearing potential must have a negative serum or urine pregnancy test within 14 days prior to the first dose of study drug. Female subjects of childbearing potential must be using two acceptable methods of contraception, from the time of screening and for the duration of the study, through study completion and for 3 months following study completion
  • Age \> 18 years.
  • Able to communicate well with the investigator, to understand and comply with the requirements of the study. Understand and sign the written informed consent.
  • Patients must give written informed consent
  • No concurrent treatment with other experimental drugs or anti-cancer drugs
  • Another distinguishable malignancy will be permitted

Exclusion

  • chemotherapy, radiation therapy or any other anticancer therapy within 4 weeks of the first dose of study drug.
  • Participation in any clinical investigation within 4 weeks prior to initial dosing.
  • known hypersensitivity to RAD001 or other rapamycin analogs and paclitaxel or other taxanes, or to its excipients.
  • previously received RAD001, other mTOR inhibitors or taxanes or epothilones
  • known metastasis of central nervous system.
  • symptomatic pleural effusions or symptomatic ascites.
  • wide field radiation therapy to up to ≥ 25% of the bone marrow within 4 weeks prior therapy.
  • intravenous radionuclide therapy, e.g. phosphorus (32P), strontium (89SrCl), rhenium (186Re)or samarium (153Sm).
  • Patients who have undergone major surgery within 4 weeks prior to starting study drug,open biopsy, or significant traumatic injury, or who have not recovered from the side effects of any of the above.
  • Chronic systemic treatment with corticosteroids corresponding to a prednisone equivalent of \> 10 mg daily. Patients receiving corticosteroids must be on a stable dose for ≥ 4 weeks prior to the first dose of RAD001. Topical or inhaled corticosteroids are permitted.
  • Concomitant medication with strong CYP3A4- inhibitors or CYP3A4- inducers.
  • active bleeding diathesis.
  • Neuropathy \> grade 1.
  • any severe and/or uncontrolled medical conditions(unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction ≤ 6 months, serious uncontrolled cardiac arrhythmia, uncontrolled hyperlipidemia, active or uncontrolled severe infection,cirrhosis,chronic or persistent active hepatitis)
  • severely impaired lung function as defined as spirometry and DLCO that is 50% of the normal predicted value and/or O2 saturation ≤ 88% at rest on room air
  • Uncontrolled diabetes
  • Hepatic impairment with a Child-Pugh score \>9

Key Trial Info

Start Date :

July 1 2009

Trial Type :

INTERVENTIONAL

Allocation :

ACTUAL

End Date :

September 1 2013

Estimated Enrollment :

28 Patients enrolled

Trial Details

Trial ID

NCT00933374

Start Date

July 1 2009

End Date

September 1 2013

Last Update

March 18 2015

Active Locations (6)

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Page 1 of 2 (6 locations)

1

Klinik für Urologie, Klinikum rechts der Isar der TU München

München, Bavaria, Germany, 81675

2

Universitätsklinik Hamburg, Medizinische Klinik und Poliklinik Onkologie - Hämatologie

Hamburg, Hamburg, Germany, 20246

3

Heinrich-Heine-University of Duesseldorf, Department of Urology

Düsseldorf, North Rhine-Westphalia, Germany, 40225

4

Universitätsklinik Essen, Klinik für Urologie

Essen, North Rhine-Westphalia, Germany, 45122