Study of Pralatrexate to Treat Advanced or Metastatic Relapsed Transitional Cell Carcinoma of the Urinary Bladder
Condition: Carcinoma, Transitional Cell; Bladder Cancer; Bladder Neoplasm
MeSH terms: Carcinoma; Urinary Bladder Neoplasms; Carcinoma, Transitional Cell
Intervention: Pralatrexate Injection; Vitamin B12; Folic Acid
Intervention description: Intravenous (IV) push administration over 3-5 minutes via a peripheral IV line containing normal saline (0.9% sodium chloride).
Initial dose: 190 mg/m2
Dose reductions per protocol: 150 mg/m2, 120 mg/m2 and 100 mg/m2 will be allowed for defined toxicity.
Administered on days 1 and 15 of a 4-week cycle (every 2 weeks) until criteria for discontinuation per the protocol are met.; 1 mg intramuscular injection
Administered within 10 weeks of enrollment, every 8-10 weeks throughout the study and for at least 30 days after last dose of pralatrexate.; 1-1.25 mg orally
Administered daily for at least 7 days prior to enrollment, throughout the study and for at least 30 days after last dose of pralatrexate.
Intervention MeSH terms: Vitamins; Folic Acid; Vitamin B 12; Vitamin B Complex; 10-deazaaminopterin; Aminopterin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 30.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Transitional Cell Carcinoma of the Urinary Bladder; Transitional Cell Carcinoma; Bladder Cancer; Urinary Bladder Cancer; Bladder; Carcinoma; Urinary; Metastatic; Relapsed

Summary:

      The purpose of this study is to determine whether pralatrexate, given with vitamin B12 and
      folic acid, is effective in the treatment of advanced or metastatic bladder cancer. The study
      will also investigate the safety of pralatrexate with vitamin B12 and folic acid in this
      patient population. Additionally, this study includes the collection of blood samples to
      investigate the pharmacokinetics (PK) of pralatrexate in this patient population (PK is the
      activity of a drug in the body over a period of time, including how the drug is absorbed,
      distributed in the body, localized in the tissues, and excreted from the body).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed transitional cell carcinoma of the urinary bladder. Fine
             needle aspirate will not be accepted.

          -  Relapsed or progressed after treatment with a platinum- and/or methotrexate-based
             systemic chemotherapy regimen. No more than 1 prior regimen is permitted for
             recurrent/metastatic disease. Patients has had a chemotherapy-free interval of ≥ 12
             months from last dose if most recent prior chemotherapy was in neoadjuvant/adjuvant
             setting and has had ≥ 6-month chemotherapy-free interval in 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.

          -  Measurable disease outside a previously irradiated region, per Response Evaluation
             Criteria in Solid Tumors (RECIST).

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

          -  At least 18 years of age.

          -  Adequate blood, liver, and kidney function as defined by laboratory results.

          -  Patient has received 1.0-1.25 mg of oral folic acid daily for at least 7 days of
             enrollment & 1 mg intramuscular vitamin B12 within 10 weeks of enrollment.

          -  Women of childbearing potential have a negative serum pregnancy test within 14 days
             prior to enrollment and agree to use medically acceptable and effective birth control
             from enrollment until at least 30 days after the last dose of pralatrexate.

          -  Men who are not surgically sterile and whose partner is of childbearing potential must
             use medically safe and effective birth control start of pralatrexate until at least 90
             days after the last dose of pralatrexate.

          -  Accessible for repeat dosing and follow up.

          -  Give written informed consent.

        Exclusion Criteria:

          -  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). 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 < 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.

          -  More than 1 previous regimen for recurrent/metastatic disease.

          -  Evidence of clinically significant active third-space phenomenon

          -  Use of investigational drugs, biologics, or devices within 28 days prior to study
             enrollment.

          -  Previous exposure to other antifolates, including pralatrexate. Previous methotrexate
             is allowed, only if it was part of an M-VAC or MCV regimen.

          -  Women who are pregnant or breastfeeding.

          -  Congestive Heart Failure Class III/IV according to New York Heart Association (NYHA)
             Functional Classification.

          -  Uncontrolled hypertension.

          -  Human immunodeficiency virus (HIV)-positive diagnosis with a CD4 count of < 100 mm3 or
             detectable viral load within the past 3 months, and receiving combination
             anti-retroviral therapy.

          -  Central nervous system metastatic disease.

          -  Major surgery within 2 weeks of study enrollment.

          -  Radiation therapy (RT) within 4 weeks (within 3 months for RT to the pelvis) prior to
             study enrollment.

          -  Active infection or any serious underlying medical condition, which would impair the
             ability of the patient to receive protocol treatment.

          -  Dementia or significantly altered mental status that would prohibit the understanding
             and giving of informed consent or limit study compliance.