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

Phase 1

• Conditions: Advanced or Metastatic Relapsed Transitional Cell Carcinoma of the Urinary Bladder; MedDRA version: 13.1Level: LLTClassification code 10007294Term: Carcinoma bladder recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

• Registration Number: EUCTR2007-004671-19-BE
• Lead Sponsor: Allos Therapeutics, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-03-27
• Last Update Posted: 21 August 2017

Recruitment & Eligibility

• Status: ot Recruiting
• 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 or progressed after treatment with a platinum- and/or methotrexate-based systemic chemotherapy regimen. No more than 1 prior regimen is permitted in the recurrent/metastatic setting. Patient has had a chemotherapy-free interval of at least 12 months from the last dose of chemotherapy if the most recent prior regimen was in the neoadjuvant or adjuvant setting and has had at least a 6-month chemotherapy-free interval from regimens in the recurrent/metastatic setting. 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 from the procedure.
3. Measurable disease, outside a previously irradiated region, per Response Evaluation Criteria in Solid Tumors (RECIST) (see http://www.eortc.be/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 10^9 cells/L); absolute neutrophil count (ANC)= 1500 cells/mm3 (= 1.5 x 10^9 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 or prior malignancies occurring within 5 years (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 malignancies other than those exceptions listed above, the patient must be disease free for = 5 years. Patients with other prior malignancies less than 5 years before study entry may still be enrolled if they have received treatment resulting in complete resolution of the cancer and currently have no clinical, radiologic, or laboratory evidence of active or recurrent disease. 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 1 previous chemotherapeutic regimen in the recurrent/metastatic setting.
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 methotrexate, vinblastine, doxorubicin (Adriamycin), and cisplatin (M-VAC) or methotrexate, cisplatin, and vinblastine (MCV) regimen.
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. Human immunodeficiency virus (HIV)-positive diagnosis with a CD4 count of < 100 mm3 or detectable viral load within the past 3 months, and is receiving combination anti-retroviral therapy.
11. CNS metastatic disease.
12. Major surgery within 2 weeks of study enrollment.
13. Radiation therapy within 4 weeks (within 3 months for RT to the pelvis) 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