A Phase 2, Single-Arm Study of Pralatrexate in Patients with Advancedor Metastatic Relapsed Transitional Cell Carcinoma of the Urinary Bladder

Conditions: Advanced or Metastatic Relapsed Transitional Cell Carcinoma of the Urinary Bladder
MedDRA version: 9.1Level: LLTClassification code 10007294Term: Carcinoma bladder recurrent

Registration Number: EUCTR2007-004671-19-FR

Lead Sponsor: Allos Therapeutics, Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 50

Inclusion Criteria

1. Histologically confirmed TCC (> 50% TCC in tumor) of the urinary bladder. Fine needle aspirate will not be accepted.
2. Relapsed after treatment with no more than 1 platinum-based systemic chemotherapy regimen for metastatic disease or relapsed within 6 months of previous platinum-based neoadjuvant/adjuvant therapy. Patient has recovered from the toxic effects of prior therapy. Previous intravesical therapy is allowed. Prior surgical resection is allowed, as long as the patient has recovered.
3. Measurable disease, outside a previously irradiated region, per Response Evaluation Criteria in Solid Tumors (RECIST).
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
5. = 18 years of age.
6. Adequate hematologic, hepatic, and renal function as defined by: Hgb = 10 g/dL (= 100 g/L); WBC count = 2500 cells/mm3 (= 2.5 x 109 cells/L); absolute neutrophil count (ANC)= 1500 cells/mm3 (= 1.5 x 109 cells/L); platelet count = 100,000/mm3; calculated CrCl of = 50 mL/min; total bilirubin = 1.5 x upper limit of normal (ULN); and aspartate aminotransferase (AST, serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT, serum glutamic-pyruvic transaminase [SGPT]) = 3 x ULN.
7. The patient has been on a regimen of 1-1.25 mg PO QD of folic acid for at least 7 days prior to enrollment and has received 1 mg IM of vitamin B12 within 10 weeks of enrollment.
8. Women of childbearing potential have a negative serum pregnancy test within 14 days prior to enrollment and must agree to practice a medically acceptable contraceptive regimen from enrollment until at least 30 days after the last administration of pralatrexate. Patients who are postmenopausal for at least 1 year (> 12 months since last menses) or are surgically sterilized do not require this test.
9. Men who are not surgically sterile and whose partner is of childbearing potential must be practicing a medically safe and effective contraceptive regimen from the time of pralatrexate initiation, and agree to continue practicing until at least 90 days after the last administration of pralatrexate.
10. Accessible for repeat dosing and follow-up.
11. Given written informed consent (IC).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Active concurrent primary malignancy (except non-melanoma skin cancer, in situ carcinoma of the cervix, or occult, indolent carcinoma of the prostate [undetectable prostate-specific antigen, Gleason score = 7, no seminal vesicle invasion, and no extraprostatic extension]). If there is a history of prior malignancy, the patient must be disease-free for = 5 years. In the case of a single extrapelvic metastatic site, irrespective of the patient having a history of previous malignancy, a biopsy proof of the metastatic diseased organ will be necessary.
2. More than one previous regimen for either neoadjuvant/adjuvant or advanced disease (except simultaneous chemoradiotherapy).
3. Evidence of clinically significant active thirdspace phenomenon; ie, peripheral edema (= +2), active pleural effusions, or ascites.
4. Use of any investigational drugs, biologics, or devices within 28 days prior to study
enrollment.
5. Previous exposure to other antifolates (eg, methotrexate, pemetrexed [Alimta]). Previous methotrexate is allowed, only if it was part of a M-VAC or MCV regimen and provided that 6 months has elapsed since treatment with M-VAC or MCV.
6. Previous exposure to pralatrexate.
7. Women who are pregnant or breastfeeding.
8. Congestive Heart Failure Class III/IV according to New York Heart Association (NYHA) Functional Classification.
9. Uncontrolled hypertension.
10. Known human immunodeficiency virus (HIV)-positive status.
11. CNS metastatic disease.
12. Major surgery within 2 weeks of study enrollment.
13. Receipt of any conventional systemic chemotherapy or RT within 4 weeks (6 weeks for nitrosoureas, mitomycin C) prior to study enrollment.
14. Active infection or any serious underlying medical condition, which would impair the ability of the patient to receive protocol treatment.
15. Dementia or significantly altered mental status that would prohibit the understanding and giving of IC or limit study compliance.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To determine the objective response rate (CR + PR) for pralatrexate with concurrent vitamin B12 and folic acid supplementation in the treatment of patients with advanced or metastatic relapsed TCC (Transitional Cell Carcinoma) of the urinary bladder.;Secondary Objective: 1. To determine the duration of response, clinical benefit rate, progression-free survival (PFS), and overall survival (OS) in patients with advanced or metastatic relapsed TCC of the urinarybladder treated with pralatrexate.<br><br>2. To evaluate the safety and tolerability of administration of pralatrexate with concurrent vitamin B12 and folic acid supplementation in patients with advanced or metastatic relapsed TCC of the urinary bladder.;Primary end point(s): Objective response

Secondary Outcome Measures

Name	Time	Method

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