Trial to Evaluate Paclitaxel Plus RAD001 in Urothelial Carcinoma

NCT00933374 | Terminated Phase 2 DMC

• 1 other identifier: CRAD001L DE 17T
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 6

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.

Conditions

Bladder Cancer

Keywords

bladder cancer; RAD001; Paclitaxel

Outcome Measures

Primary Outcomes (1)

• Response rate

  3 years

Secondary Outcomes (4)

• Duration of response

  from first determination of response until progression

• Progression free survival

  3 years

• overall survival

  3 years

• safety profile of combination RAD001 and paclitaxel

  6 month

Study Arms (1)

Paclitaxel and RAD001

EXPERIMENTAL

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; Drug: RAD001

Interventions

paclitaxel DRUG

Paclitaxel (175 mg/m3)will be administered as a 3 hour continuous IV infusion after standard premedication every 3 weeks

Also known as: Taxol

Paclitaxel and RAD001

RAD001 DRUG

10 mg RAD001 once daily starting at day 1 of a 21 days treatment cycle

Also known as: Certican, Everolimus

Paclitaxel and RAD001

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Heinrich-Heine University, Duesseldorf: lead

Study Sites (6)

Klinik für Urologie, Klinikum rechts der Isar der TU München

München, Bavaria, 81675, Germany

Location

Universitätsklinik Hamburg, Medizinische Klinik und Poliklinik Onkologie - Hämatologie

Hamburg, Hamburg, 20246, Germany

Location

Heinrich-Heine-University of Duesseldorf, Department of Urology

Düsseldorf, North Rhine-Westphalia, 40225, Germany

Location

Universitätsklinik Essen, Klinik für Urologie

Essen, North Rhine-Westphalia, 45122, Germany

Location

Klinik für Urologie, Universitätsklinikum Muenster

Münster, North Rhine-Westphalia, 48149, Germany

Location

Klinik für Urologie und Kinderurologie, Universitätsklinikum des Saarlandes

Homburg, Saarland, 66421, Germany

Location

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

Paclitaxel; Everolimus

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Sirolimus; Macrolides; Lactones

Study Officials

• Peter Albers, Professor

  Heinrich-Heine-University, Department of Urology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 3, 2009
• First Posted: July 7, 2009
• Study Start: July 1, 2009
• Primary Completion: January 1, 2013
• Study Completion: September 1, 2013
• Last Updated: March 18, 2015

Record last verified: 2015-03

Locations

DE (6)