Phase 1/2 Study of Biweekly ALIMTA plus Cisplatin in patients with Locally Advanced, non-Resectable or Metastatic Urothelial Cancer
- Conditions
- ocally Advanced, non-Resectable or Metastatic Urothelial Cancer
- Registration Number
- EUCTR2004-004149-16-ES
- Lead Sponsor
- illy S.A.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 57
[1] Histologic or cytologic diagnosis of locally advanced or metastatic cancer with no standard potentially curative therapy.
[2]Performance status 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale.
[3]Measurable or non measurable disease.
[4]Estimated life expectancy of at least 12 weeks.
[5]Prior radiation to the whole pelvis is not allowed. Prior palliative radiation therapy allowed if completed at least 2 weeks prior to study enrollment.
[6]Patient compliance and geographic proximity that allow adequate follow-up.
[7]Adequate organ function including the following:Adequate bone marrow reserve: platelets ³100 x 109/L, hemoglobin ³90 g/L, absolute neutrophil count (ANC) ³1.5 x 109/L.Hepatic: bilirubin £1.5 times the upper limit of normal (x ULN); alkaline phosphatase (AP), aspartate transaminase (AST), and alanine transaminase (ALT) <3 x ULN, or <5 x ULN with liver metastases. ·Adequate renal function (Creatinine Clearance (CrCl) (>45 mL/min). CrCl will be assessed by calculation from serum/plasma creatinine formula (Cockcroft and Gault) or directly measured. If done measured value will take precedent over calculated. Urological procedures (such as ureteral stent (i.e. double j catheter) or percutaneous nephrostomy) are allowed prior to inclusion in the trial in order to relieve urinary tract obstruction and to improve renal function.
[8] Signed informed consent from patient.
[9]At least 18 years of age.
[10]Patients must take medically approved contraceptive precautions (if necessary) during the trial and for 3 months afterwards. Females with childbearing potential must have a negative serum pregnancy test within 7 days prior to study enrollment.
Inclusion criteria for Phase II:
[1]Histologically proven stage IV locally advanced disease (T4 b any N, or any T N2-3 ) or metastatic (M1) transitional cell carcinoma of the urothelium (pure or mixed) including bladder, urethra, ureter, and renal pelvis. Patients should not be suitable for surgery or radiation with curative intent. However patients whose pre-chemotherapy sites of disease are restricted to the primary or regional lymph node sites and who have a major response to chemotherapy will be evaluated for post-chemotherapy surgical resection of residual cancer if the tumor has become resectable at the end of chemotherapy.
[2]Measurable disease status, as defined in the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Patients must have measurable disease that is outside a previously irradiated area or a new lesion that has grown in a previous irradiated area.
[3]One course of prior radiation therapy is allowed. Prior radiation must have been completed at least 4 weeks before enrolment into the study and the patients must have recovered from all toxic effects.
[4]Patients may have previously received one neoadjuvant and/or adjuvant chemotherapy regimen. No previous chemotherapy for metastatic disease.
[5]ECOG performance status of 0, 1, or 2
[6] Estimated life expectancy ³ 12 weeks.
[7] Patient compliance and geographic proximity that allow adequate follow-up
[8] Adequate organ function including the following:Adequate bone marrow reserve: platelets ³100 x 109/L, hemoglobin ³90 g/L, absolute neutrophil count (ANC) ³1.5 x 109/L.Hepatic: bilirubin £1.5 times the upper limit of normal (x ULN); alkaline phosphatase (AP), aspartate transaminase (AST), and alanine transaminase (ALT) <3 x ULN, or <5 x
[1]Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry
[2] Have received other forms of chemotherapy within the four weeks prior to enrollment
[3]Have central nervous system (CNS) or leptomeningeal metastases (unless the patient has completed successful local therapy for CNS metastases and has been off corticosteroids for at least 4 weeks before starting study therapy). A screening CT or MRI before enrollment in the absence of a clinical suspicion of brain metastases is not required.
[4]Pregnancy or breast-feeding.
[5]Serious concomitant systemic disorders (e.g, active infection) that, in the opinion of the investigator, would compromise the safety of the patient and his or her ability to complete the study. Patients previously treated with a nephrotoxic antibiotic are at risk of further toxicity due to cisplatin and should be very carefully monitored..
[6]Inability to interrupt aspirin or other nonsteroidal anti-inflammatory agents 2 days before, the day of, and 2 days after the dose of ALIMTA plus cisplatin or cisplatin alone. If a patient is taking a NSAID or salicylate with a long half-life (for example, naproxen, piroxicam, diflunisal) it should not be taken 5 days before the dose of ALIMTA (8-day period for long-acting agents such as piroxicam), the day of, and 2 days after the dose of ALIMTA plus cisplatin or cisplatin alone.
[7]Presence of clinically significant third-space fluid collections (for example, ascites or pleural effusions).
[8]Inability or unwillingness to take folic acid or vitamin B12 supplementation.
[9]Grade 2 or greater peripheral neuropathy according to the CTC, version 3.0.
[10]Presence of any clinically significant cardiac arrhythmia, congestive heart failure, or complete bundle branch block functional Class III or worse, according to the New York Heart Association (NYHA.)
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method