Study of Pralatrexate to Treat Advanced or Metastatic Relapsed Transitional Cell Carcinoma of the Urinary Bladder

NCT00722553 | Completed Phase 2 Results

• 2 other identifiers: PDX-0112007-004671-19
• Study Type: interventional
• Target: 30
• Locations: 6 countries
• Sites: 19

Brief 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).

Conditions

Carcinoma, Transitional Cell; Bladder Cancer; Bladder Neoplasm

Keywords

Transitional Cell Carcinoma of the Urinary Bladder; Transitional Cell Carcinoma; Bladder Cancer; Urinary Bladder Cancer; Bladder; Carcinoma; Urinary; Metastatic; Relapsed

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  The number of patients with a best overall confirmed response of either complete response (CR) or partial response (PR)

  Assessed at the end of each even-numbered cycle (every 8 weeks), or per standard of care but no more than every 12 weeks (+/- 1 week) if treatment has ended for up to 2 years after enrollment.

Secondary Outcomes (4)

• Duration of Response (DOR)

  Measured from the first day of documented response for up to 2 years after enrollment.

• Clinical Benefit Rate (CBR)

  Assessed at the end of each even-numbered cycle (every 8 weeks) or per standard of care, but no more than every 12 weeks (+/- 1 week) if treatment has ended, for up to 2 years after enrollment.

• Progression Free Survival (PFS)

  Assessed at the end of each even-numbered cycle (every 8 weeks), or per standard of care but no more than every 12 weeks (+/- 1 week) if treatment has ended, for up to 2 years after enrollment.

• Overall Survival (OS)

  Assessed at the end of each even-numbered cycle (every 8 weeks), or per standard of care if treatment has ended (at least every 12 weeks) for up to 2 years after enrollment. After PD or start of subsequent treatment, OS will be assessed every 4 months.

Study Arms (1)

Dietary Supplement Vitamin B12 & Folic Acid (Vitamin B9)

OTHER

Vitamin B12 : 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. Folic Acid: 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.

Drug: Pralatrexate Injection; Dietary Supplement: Vitamin B12; Dietary Supplement: Folic Acid

Interventions

Pralatrexate Injection DRUG

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.

Also known as: FOLOTYN, PDX, Pralatrexate, (RS)-10-propargyl-10-deazaaminopterin

Dietary Supplement Vitamin B12 & Folic Acid (Vitamin B9)

Vitamin B12 DIETARY_SUPPLEMENT

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.

Also known as: Cyanocobalamin

Dietary Supplement Vitamin B12 & Folic Acid (Vitamin B9)

Folic Acid DIETARY_SUPPLEMENT

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.

Also known as: Vitamin B9, Folate, Folacin

Dietary Supplement Vitamin B12 & Folic Acid (Vitamin B9)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Acrotech Biopharma Inc.: lead

Study Sites (19)

The University of Arizona Health Sciences Center

Tucson, Arizona, 85724, United States

Location

Peachtree Hematology/Oncology Consultants

Atlanta, Georgia, 30318, United States

Location

University of Rochester Cancer Center

Rochester, New York, 14642, United States

Location

University of Utah, Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

Centro de Terapia Radiante Cumbres (CAICI)

Rosario, Santa Fe Province, 2000, Argentina

Location

IONC (Instituto Oncológuci de Cordoba)

Córdoba, X5004BAL, Argentina

Location

Algemeen Ziekenhuis Middelheim

Antwerp, 2020, Belgium

Location

Institut Jules Bordet

Brussels, 1000, Belgium

Location

CH Split Clinic of Oncology and Radiotherapy

Split, 21000, Croatia

Location

CHU Zagreb University Hospital Center Rebro in Zagreb

Zagreb, 10000, Croatia

Location

Clinic of Oncology and Nuclear Medicine, CH "Sestre Milosrdnice"

Zagreb, 10000, Croatia

Location

Institut Sainte Catherine

Avignon, 84082, France

Location

Centre Oscar Lambret

Lille, 59020, France

Location

Centre Hospitalier Rene Dubos

Pontoise, 95301, France

Location

Hopital Foch

Suresnes, France

Location

Institut Gustave Roussy

Villejuif, 94 805, France

Location

Ciutat Sanitari de Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Del Mar - Barcelona

Barcelona, 8003, Spain

Location

Hospital Virgen del Rocio

Seville, 41013, Spain

Location

MeSH Terms

Conditions

Carcinoma, Transitional Cell; Urinary Bladder Neoplasms; Carcinoma; Neoplasm Metastasis; Recurrence

Interventions

10-propargyl-10-deazaaminopterin; Vitamin B 12; Folic Acid

Condition Hierarchy (Ancestors)

Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Disease Attributes

Intervention Hierarchy (Ancestors)

Corrinoids; Tetrapyrroles; Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Macrocyclic Compounds; Polycyclic Compounds; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring

Results Point of Contact

• Title: Medical Monitor
• Organization: Allos Therapeutics, Inc.

gweems@allos.com

303-426-6262

Study Officials

• Garry Weems, Pharm.D.

  Spectrum Pharmaceuticals, Inc

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 23, 2008
• First Posted: July 25, 2008
• Study Start: July 1, 2008
• Primary Completion: April 1, 2011
• Study Completion: September 1, 2011
• Last Updated: December 17, 2019
• Results First Posted: July 17, 2012

Record last verified: 2019-12

Locations

AR (2); US (4); BE (2); FR (5); ES (3); CR (3)