Stage IV urothelial Cancer Cáncer de urotelio estadío 4
Conditions
Interventions
Product Name: AZD4877
Product Code: AZD4877
Pharmaceutical Form: Solution for infusion
CAS Number: 876308-78-0
Current Sponsor code: AZD4877
Concentration unit: mg/ml milligram(s)/millilitre
Concentra
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Provision of written informed consent 2.Male or female age =18 years 3.Histologically confirmed transitional cell carcinoma (TCC) of the urothelium (bladder, renal pelvis, ureter, or urethra). Mixed histology is allowed as long as the predominant histology is TCC 4.TNM Stage IV disease (see Appendix G) that is not amenable to curative surgery and/or radiotherapy 5.First recurrence after treatment with a maximum of two chemotherapeutic regimens, one of which must have been for unresectable and/or locally advanced disease, and the other of which must have been in either the adjuvant or neo-adjuvant setting. 6.Measurable disease per RECIST criteria (Appendix D). Previously irradiated lesions are not considered measurable 7.Eastern cooperation Oncology Group (ECOG) performance status of 0, 1, or 2 (Appendix C) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1.Prior treatment with investigational or standard anti-cancer agents, including radiotherapy, within 4 weeks prior to first dose of study treatment; 6 weeks if prior systemic mitomycin, nitrosourea, or suramin. One exception to this is palliative radiotherapy given (up to one week prior to study entry) for pain to non-target lesion bony metastases. Another exception to this is hormonal therapy for prostate cancer. 2.Inadequate bone marrow reserve as demonstrated by absolute neutrophil count (ANC) 2.5 x upper limit of normal (ULN); >5 x ULN in the presence of liver metastases 4.Impaired renal function, defined by creatinine >1.5 x ULN or creatinine clearance <40 mL/min, estimated by Cockcroft-Gault equation or measured via 24 h urine creatinine 5.Any evidence of severe or uncontrolled systemic diseases including known cases of Hepatitis B or C or human immunodeficiency virus (HIV). Screening for chronic conditions is not required, although patients known to have such conditions at screening should not be included 6.Unresolved toxicity greater than CTCAE grade 1 from previous anti-cancer therapy (excluding neurotoxicity or alopecia) or incomplete recovery or healing from previous surgery, unless agreed by AZ and the PI with documentation 7.Presence of currently active CNS involvement or clinical evidence of active CNS disease. 8.Patients with massive pleural effusions or ascites unless drained 9.Pregnancy or breast-feeding. Women of childbearing potential must have a negative pregnancy test prior to starting first dose of study treatment 10.Any severe concomitant condition which, in the opinion of the PI, makes it undesirable for the patient to participate in the study or which could jeopardize compliance with the protocol 11.Involvement in the planning and conduct of the study (applies to both AZ staff and study centre personnel) 12.Major surgery, in the opinion of the PI, within 4 weeks prior to first dose of study treatment 13.Incomplete healing from prior bladder surgery, biopsy, or exenteration, or if surgical revisions anticipated in next 2 months after study entry 14.Previous (within the last 5 years) or concurrent malignancies of other histologies, with the exception of cervical carcinoma in situ, adequately treated basal cell, squamous cell carcinoma of the skin, or prostate cancer 15.Use of any known significant modulators of CYP3A4 within 2 weeks of the first dose of AZD4877 and until Cycle 1, Day 8: Barbiturates including primidone, carbamazepine drugs including oxcarbazepine, clarithromycin, erythromycin, fluconazole, griseofulvin, hydantoins, itraconazole, ketoconazole, miconazole, nefazodone, rifampicin, troleandomycin, protease inhibitors, St. John’s wort, grapefruit juice and Seville orange juice (Preceding agents may be used after Cycle 1 Day 8 if deemed medically necessary by the PI and AZ) 16.Previous participation in any AZD4877 study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the effect of AZD4877 on the objective response rate (ORR) in patients with recurrent advanced urothelial cancer receiving AZD4877 at the selected dose level of 25 mg once weekly, with response including complete response (CR) or partial response (PR) as assessed by Response Evaluation Criteria In Solid Tumours (RECIST);Secondary Objective: To describe the efficacy of AZD4877 in terms of disease control rate (DCR: CR, PR, and durable stable disease (SD)), duration of objective tumour response (DoR), progression-free survival (PFS) and overall survival (OS) To evaluate the safety and tolerability of AZD4877 by assessment of adverse events (AE), changes in laboratory values, vital signs and incidence of protocol-defined dose modifications or omissions To evaluate the pharmacokinetics (PK) of AZD4877 in urothelial cancer patients by Cmax ;Primary end point(s): The primary efficacy variable is: ORR: defined as the proportion of patients with CR or PR as per RECIST. CR and PR must be confirmed 4 weeks later, as described in Appendix D. Patients without sufficient information (including missing values) for response assessment will be considered non-responders | — |
Countries
Germany, Spain, United Kingdom
Outcome results
None listed