Trial to Evaluate Paclitaxel Plus RAD001 in Urothelial Carcinoma (RAD001)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00933374
Recruitment Status : Terminated (delayed recruitment)
First Posted : July 7, 2009
Last Update Posted : March 18, 2015
Information provided by (Responsible Party):
Heinrich-Heine University, Duesseldorf

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 therapy.

Condition or disease Intervention/treatment Phase
Bladder Cancer Drug: paclitaxel Drug: RAD001 Phase 2

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 histological or cytological.Patients who meet the inclusion criteria will be treated with paclitaxel 175 mg/m2 every 3 weeks and RAD001 10 mg once daily. Each cycle will use the combination of paclitaxel 175 mg/m2 3-weekly with RAD001 10 mg daily starting at day 1 of a 21 days treatment cycle. Additional visits after day 1 are performed at day 8 and day 15 of each cycle Assessment of safety and toxicity will be performed at every visit.

Patients will be treated until no signs of clinical or radiological progression are evident and the study treatment is well tolerated for a maximum of 6 cycles.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 28 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Single Arm, Multi-center Phase II Trial to Evaluate Paclitaxel Plus RAD001 in Urothelial Carcinoma After Failure of Prior Platin-based Chemotherapy
Study Start Date : July 2009
Actual Primary Completion Date : January 2013
Actual Study Completion Date : September 2013

Arm Intervention/treatment
Experimental: Paclitaxel and RAD001
175 mg /m3 paclitaxel every 3 weeks and 10 mg RAD001 once daily starting at day 1 of a 21 days treatment cycle
Drug: paclitaxel
Paclitaxel (175 mg/m3)will be administered as a 3 hour continuous IV infusion after standard premedication every 3 weeks
Other Name: Taxol
Drug: RAD001
10 mg RAD001 once daily starting at day 1 of a 21 days treatment cycle
Other Name: Certican, Everolimus

Primary Outcome Measures :
  1. Response rate [ Time Frame: 3 years ]

Secondary Outcome Measures :
  1. Duration of response [ Time Frame: from first determination of response until progression ]
  2. Progression free survival [ Time Frame: 3 years ]
  3. overall survival [ Time Frame: 3 years ]
  4. safety profile of combination RAD001 and paclitaxel [ Time Frame: 6 month ]

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 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 Criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00933374

Klinik für Urologie, Klinikum rechts der Isar der TU München
München, Bavaria, Germany, 81675
Heinrich-Heine-University of Duesseldorf, Department of Urology
Duesseldorf, NRW, Germany, 40225
Universitätsklinik Essen, Klinik für Urologie
Essen, NRW, Germany, 45122
Klinik für Urologie, Universitätsklinikum Muenster
Muenster, NRW, Germany, 48149
Klinik für Urologie und Kinderurologie, Universitätsklinikum des Saarlandes
Homburg, Saarland, Germany, 66421
Universitätsklinik Hamburg, Medizinische Klinik und Poliklinik Onkologie - Hämatologie
Hamburg, Germany, 20246
Sponsors and Collaborators
Heinrich-Heine University, Duesseldorf
Principal Investigator: Peter Albers, Professor Heinrich-Heine-University, Department of Urology

Responsible Party: Heinrich-Heine University, Duesseldorf Identifier: NCT00933374     History of Changes
Other Study ID Numbers: CRAD001L DE 17T
First Posted: July 7, 2009    Key Record Dates
Last Update Posted: March 18, 2015
Last Verified: March 2015

Keywords provided by Heinrich-Heine University, Duesseldorf:
bladder cancer

Additional relevant MeSH terms:
Urinary Bladder Neoplasms
Carcinoma, Transitional Cell
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Urinary Bladder Diseases
Urologic Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents