Summary
EudraCT Number:2004-003055-40
Sponsor's Protocol Code Number:Son-8184-1073
National Competent Authority:Spain - AEMPS
Clinical Trial Type:EEA CTA
Trial Status:Ongoing
Date on which this record was first entered in the EudraCT database:2006-01-30
Trial results
A. Protocol Information
A.1Member State ConcernedSpain - AEMPS
A.2EudraCT number2004-003055-40
A.3Full title of the trial
A PHASE 2 MULTICENTER EVALUATION OF THE
SAFETY AND EFFICACY OF TOCOSOL™ PACLITAXEL
(S-8184 PACLITAXEL INJECTABLE EMULSION) IN
PATIENTS WITH METASTATIC OR LOCALLY ADVANCED, UNRESECTABLE TRANSITIONAL CELL CARCINOMA OF THE UROTHELIUM
A.4.1Sponsor's protocol code numberSon-8184-1073
A.7Trial is part of a Paediatric Investigation Plan Information not present in EudraCT
A.8EMA Decision number of Paediatric Investigation Plan
B. Sponsor Information
B.Sponsor: 1
B.1.1Name of SponsorSONUS Pharmaceuticals Inc.
B.1.3.4CountryUnited States
B.3.1 and B.3.2Status of the sponsorNon-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1Name of organisation providing support
B.4.2Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1Name of organisation
B.5.2Functional name of contact point
D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3IMP RoleTest
D.2 Status of the IMP to be used in the clinical trial
D.2.1IMP to be used in the trial has a marketing authorisation Information not present in EudraCT
D.2.1.1.1Trade name TOCOSOL
D.2.1.1.2Name of the Marketing Authorisation holderSonus Pharmaceuticals Inc.
D.2.1.2Country which granted the Marketing AuthorisationUnited States
D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
D.2.5.1Orphan drug designation number
D.3 Description of the IMP
D.3.1Product nameTOCOSOL
D.3.2Product code S-8184
D.3.4Pharmaceutical form Intravenous infusion
D.3.4.1Specific paediatric formulation Information not present in EudraCT
D.3.7Routes of administration for this IMPIntravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNpaclitaxel
D.3.10 Strength
D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
D.3.10.2Concentration typeequal
D.3.10.3Concentration number10
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin Yes
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
The IMP is a:
D.3.11.3Advanced Therapy IMP (ATIMP) Information not present in EudraCT
D.3.11.3.1Somatic cell therapy medicinal product No
D.3.11.3.2Gene therapy medical product No
D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Information not present in EudraCT
D.3.11.5Radiopharmaceutical medicinal product No
D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
D.3.11.7Plasma derived medicinal product Information not present in EudraCT
D.3.11.8Extractive medicinal product Information not present in EudraCT
D.3.11.9Recombinant medicinal product Information not present in EudraCT
D.3.11.10Medicinal product containing genetically modified organisms No
D.3.11.11Herbal medicinal product No
D.3.11.12Homeopathic medicinal product No
D.3.11.13Another type of medicinal product No
D.8 Information on Placebo
E. General Information on the Trial
E.1 Medical condition or disease under investigation
E.1.1Medical condition(s) being investigated
PATIENTS WITH METASTATIC OR LOCALLY ADVANCED, UNRESECTABLE TRANSITIONAL CELL CARCINOMA OF THE UROTHELIUM
MedDRA Classification
E.1.3Condition being studied is a rare disease No
E.2 Objective of the trial
E.2.1Main objective of the trial
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, 120mg/m2/week over 15 minutes
E.2.2Secondary objectives of the trial
* 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
* Determine if this dosing regimen (dose and schedule) of TOCOSOL Paclitaxel is well tolerated in this patient population
* At selected study sites, 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
* Obtain additional data regarding the utility of histamine blockers and corticosteroids in ameliorating infusion reactions.
E.2.3Trial contains a sub-study Information not present in EudraCT
E.3Principal 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.4Principal 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 anticonvulsants known to induce P450 isoenzymes
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).
E.5 End points
E.5.1Primary 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 (see Section 9.3) will be assessed for all eligible patients and descriptively reported with 95% confidence intervals.
E.6 and E.7 Scope of the trial
E.6Scope of the trial
E.6.1Diagnosis Information not present in EudraCT
E.6.2Prophylaxis Information not present in EudraCT
E.6.3Therapy Information not present in EudraCT
E.6.4Safety Yes
E.6.5Efficacy Yes
E.6.6Pharmacokinetic Information not present in EudraCT
E.6.7Pharmacodynamic Information not present in EudraCT
E.6.8Bioequivalence Information not present in EudraCT
E.6.9Dose response Information not present in EudraCT
E.6.10Pharmacogenetic Information not present in EudraCT
E.6.11Pharmacogenomic Information not present in EudraCT
E.6.12Pharmacoeconomic Information not present in EudraCT
E.6.13Others Information not present in EudraCT
E.7Trial type and phase
E.7.1Human pharmacology (Phase I) No
E.7.1.1First administration to humans No
E.7.1.2Bioequivalence study No
E.7.1.3Other No
E.7.1.3.1Other trial type description
E.7.2Therapeutic exploratory (Phase II) Yes
E.7.3Therapeutic confirmatory (Phase III) No
E.7.4Therapeutic use (Phase IV) No
E.8 Design of the trial
E.8.1Controlled No
E.8.1.1Randomised No
E.8.1.2Open Information not present in EudraCT
E.8.1.3Single blind Information not present in EudraCT
E.8.1.4Double blind Information not present in EudraCT
E.8.1.5Parallel group Information not present in EudraCT
E.8.1.6Cross over Information not present in EudraCT
E.8.1.7Other Information not present in EudraCT
E.8.2 Comparator of controlled trial
E.8.2.1Other medicinal product(s) No
E.8.2.2Placebo No
E.8.2.3Other No
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.8.5The trial involves multiple Member States Yes
E.8.6 Trial involving sites outside the EEA
E.8.6.1Trial being conducted both within and outside the EEA Yes
E.8.6.2Trial being conducted completely outside of the EEA Information not present in EudraCT
E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
E.8.7Trial 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.8.9.1In the Member State concerned years2
E.8.9.1In the Member State concerned months9
E.8.9.1In the Member State concerned days
E.8.9.2In all countries concerned by the trial years3
F. Population of Trial Subjects
F.1 Age Range
F.1.1Trial has subjects under 18 No
F.1.1.1In Utero Information not present in EudraCT
F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) Information not present in EudraCT
F.1.1.3Newborns (0-27 days) Information not present in EudraCT
F.1.1.4Infants and toddlers (28 days-23 months) Information not present in EudraCT
F.1.1.5Children (2-11years) Information not present in EudraCT
F.1.1.6Adolescents (12-17 years) Information not present in EudraCT
F.1.2Adults (18-64 years) Yes
F.1.3Elderly (>=65 years) Yes
F.2 Gender
F.2.1Female Yes
F.2.2Male Yes
F.3 Group of trial subjects
F.3.1Healthy volunteers No
F.3.2Patients Yes
F.3.3Specific vulnerable populations Information not present in EudraCT
F.3.3.1Women of childbearing potential not using contraception No
F.3.3.2Women of child-bearing potential using contraception Information not present in EudraCT
F.3.3.3Pregnant women No
F.3.3.4Nursing women No
F.3.3.5Emergency situation No
F.3.3.6Subjects incapable of giving consent personally No
F.3.3.7Others No
F.4 Planned number of subjects to be included
F.4.1In the member state20
F.4.2 For a multinational trial
F.4.2.1In the EEA 25
F.4.2.2In the whole clinical trial 44
G. Investigator Networks to be involved in the Trial
N. Review by the Competent Authority or Ethics Committee in the country concerned
N.Competent Authority Decision Authorised
N.Date of Competent Authority Decision2005-05-08
N.Ethics Committee Opinion of the trial applicationFavourable
N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
N.Date of Ethics Committee Opinion2005-01-25
P. End of Trial
P.End of Trial StatusOngoing