E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated | PATIENTS WITH METASTATIC OR LOCALLY ADVANCED, UNRESECTABLE TRANSITIONAL CELL CARCINOMA OF THE UROTHELIUM | |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial | To estimate the confirmed objective response rate (ORR), defined by RECIST criteria as the percentage of patients who achieve a complete response (CR) or a partial response (PR), in patients with previously treated TCC of the urothelium following administration of TOCOSOL® Paclitaxel, 100 mg/m2/week over 15 minutes. | |
E.2.2 | Secondary objectives of the trial | •To estimate time to treatment failure (TTF), time to progression (TTP), progression free survival (PFS), and 2-year overall survival (2-yr OS) in this population •To determine if this dosing regimen (dose and schedule) of TOCOSOL® Paclitaxel is well tolerated in this patient population •at selected study sites, to investigate whether there is accumulation of vitamin E in the serum, i.e., progressive rise in steady state serum vitamin E concentration after successive doses •To obtain additional data regarding the utility of histamine blockers and corticosteroids in ameliorating infusion reactions | |
E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria | a)Histologic diagnosis of TCC of the urothelium including bladder, renal pelvis, ureter, or urethra. Patients with mixed tumors (i.e. tumors containing elements of squamous cell or adenocarcinoma in addition to transitional cell carcinoma) are eligible, but patients with pure non-transitional cell carcinoma are not. b)Stage IV disease, i.e., metastatic (any T any N M1) or locally advanced (T4b N0 M0 or any T N1-3 M0) disease deemed incurable by surgical resection c)One and only one prior systemic cytotoxic chemotherapy regimen administered as adjuvant or neoadjuvant chemotherapy or to treat locally advanced or metastatic disease. (Intravesical treatments are not included in the definition of systemic cytotoxic chemotherapy.) Prior chemotherapy should have included a minimum of two cycles of standard dose MVAC (methotrexate, vinblastine, Adriamycin and cisplatin) or cis/carboplatin and gemcitabine. Other prior chemotherapy regimens of presumed comparable efficacy and dose intensity may be acceptable if approved by the Sonus Medical Director or his designee. d)Adequate hematologic function (ANC > 1500 cells/mm3 and platelet count >100,000/mm3) e)Serum creatinine < 2.0 mg/dL f)Total bilirubin < 1.5 mg/dL g)SGOT and SGPT < 3 times the upper limit of institutional normal values h)PT (INR) and PTT within institutional laboratory normal range i)Karnofsky performance status of 60-100% (see Appendix 2) j)At lease one unidimensionally measurable lesion, suitable for radiographic evaluation of disease response, consistent with RECIST criteria (see Section 9.2, Appendix 4 and Reference 14) k)A signed IRB / Ethics Committee-approved Informed Consent l)Life expectancy of at least 12 weeks m)18 years of age or older n)Fully recovered from any previous surgery (at least 4 weeks since major surgery) o)Not pregnant and willing to use a medically effective form of contraception during periods of chemotherapy treatment (both males and females, unless surgically sterilized or post-menopausal females). p)Agree not to take vitamin E supplementation while receiving study medication. q)Willing to participate in requested follow-up evaluations for 1 month after completion of treatment, or until treatment-related toxicities have resolved or clinically stabilized. r)Willing to permit treating physicians to provide information to the Sponsor regarding disease status and survival for 2 years after the first dose of study drug | |
E.4 | Principal exclusion criteria | a)Prior taxane-containing chemotherapy including Taxol (paclitaxel) or generic equivalent, or Taxotere (docetaxel) b)Peripheral neuropathy NCI-CTC grade 2 or greater c)Wide-field radiation (radiation to more than 20% of the marrow bearing skeleton), cytotoxic chemotherapy or hormonal therapy within 4 weeks of first dose, or mitomycin or nitrosoureas within 6 weeks of first dose, of study drug d)An investigational agent within 4 weeks of first dose of study drug e)Concurrent therapy with substrates known to produce clinically significant inhibition of the cytochrome P450 isoenzymes CYP2C8 or CYP3A4, e.g., dexamethasone is NOT an excluded concomitant medication. f)Patients who are pregnant or lactating g)A history of carcinoma of another primary site (other than non-melanoma skin cancers or carcinoma-in-situ of the cervix) within the previous 5 years, unless metastatic disease has been biopsied and documented to be TCC h)Bone metastasis, effusions, ascites or elevated tumor markers as the only evidence of metastatic TCC. (Patients with these findings in addition to a measurable target lesion are eligible.) i)Brain metastasis j)Active bowel obstruction k)Active, serious infection or other serious medical problems (other than TCC) likely to impair completion of the study protocol. (Any ambiguous clinical circumstances must be reviewed and approved by a Sonus Medical Director). l) Concurrent therapy with warfarin or other coumarin derivatives. | |
E.5 End points |
E.5.1 | Primary end point(s) | *Objective response rate *Median time to treatment failure *Median time to disease progression *Median progression-free survival and overall survival rate at 2 years will be assessed for all eligible patients and descriptively reported with 95% confidence intervals | |
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 | The trial involves single site in the Member State concerned | No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned | |
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 | Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial | Patients will be considered to have completed this study once they complete the Study Exit evaluation and all necessary follow-up for adverse events or serious adverse events. However, documented time to disease progression, time to treatment failure, and overall 2-year survival data will be collected for all patients. | |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |