Carcinoma, Transitional CellPhase 2NCT00722553
Study of Pralatrexate to Treat Advanced or Metastatic Relapsed Transitional Cell Carcinoma of the Urinary Bladder
A Phase 2 study testing Pralatrexate Injection, Vitamin B12 and Folic Acid in people with Carcinoma, Transitional Cell and Bladder Cancer, run by Acrotech Biopharma Inc. at 19 sites in 6 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Carcinoma, Transitional Cell, Bladder Cancer, Bladder Neoplasm
- What is being tested?
- Pralatrexate Injection, Vitamin B12 and Folic Acid
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 19 sitesin 6 countries
- Study dates
- Jul 2008to Sep 2011
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
19 sites in 6 countries.
19 sites in 6 countries
France5 sites
Institut Sainte Catherine
Avignon, 84082
Centre Oscar Lambret
Lille, 59020
Centre Hospitalier Rene Dubos
Pontoise, 95301
Hopital Foch
Suresnes
Institut Gustave Roussy
Villejuif, 94 805
United States4 sites
Peachtree Hematology/Oncology Consultants
Atlanta, Georgia, 30318
University of Rochester Cancer Center
Rochester, New York, 14642
University of Utah, Huntsman Cancer Institute
Salt Lake City, Utah, 84112
The University of Arizona Health Sciences Center
Tucson, Arizona, 85724
Croatia3 sites
CH Split Clinic of Oncology and Radiotherapy
Split, 21000
CHU Zagreb University Hospital Center Rebro in Zagreb
Zagreb, 10000
Clinic of Oncology and Nuclear Medicine, CH "Sestre Milosrdnice"
Zagreb, 10000
Spain3 sites
Ciutat Sanitari de Vall d'Hebron
Barcelona, 08035
Hospital Del Mar - Barcelona
Barcelona, 8003
Hospital Virgen del Rocio
Seville, 41013
Argentina2 sites
IONC (Instituto Oncológuci de Cordoba)
Córdoba, X5004BAL
Centro de Terapia Radiante Cumbres (CAICI)
Rosario, Santa Fe Province, 2000
Belgium2 sites
Algemeen Ziekenhuis Middelheim
Antwerp, 2020
Institut Jules Bordet
Brussels, 1000
About this study
Official title: A Phase 2, Single-Arm Study of Pralatrexate in Patients With Advanced or Metastatic Relapsed Transitional Cell Carcinoma of the Urinary Bladder
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).
- Being tested
- Pralatrexate Injection, Vitamin B12, Folic Acid
- Keywords
- Transitional Cell Carcinoma of the Urinary Bladder, Transitional Cell Carcinoma, Bladder Cancer, Urinary Bladder Cancer, Bladder, Carcinoma, Urinary, Metastatic, Relapsed
- Medical subject headings
- Carcinoma, Transitional Cell, Urinary Bladder Neoplasms, Carcinoma, Neoplasm Metastasis, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pralatrexate InjectionDrug
Also called FOLOTYN, PDX, Pralatrexate, (RS)-10-propargyl-10-deazaaminopterin
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.
Vitamin B12Dietary supplement
Also called Cyanocobalamin
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 AcidDietary supplement
Also called Vitamin B9, Folate, Folacin
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Pralatrexate Injection; Dietary Supplement: Vitamin B12; Dietary Supplement: Folic Acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate (ORR)
The number of patients with a best overall confirmed response of either complete response (CR) or partial response (PR)
Measured: 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)
Duration of time from when tumor measurement criteria were met for CR or PR (whichever status was recorded first) until the first date that recurrent disease or progressive disease (PD) or death was objectively documented. Progression is defined, using RECIST, as an increase in the smallest dimension of any target or non-target lesion, or the appearance of new lesions, since baseline. Calculated for those patients with a best overall confirmed or unconfirmed response of CR or PR.
Measured: Measured from the first day of documented response for up to 2 years after enrollment.
Clinical Benefit Rate (CBR)
The number of patients with a best confirmed or unconfirmed response of CR, PR, or stable disease (SD) for at least 24 weeks (approximately 5.5 months)
Measured: 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)
Length of time from study day 1 to the date of radiological evidence of PD (date of computed tomography [CT] or magnetic resonance imaging [MRI] scan, whichever indicates PD) or death, regardless of cause.
Measured: 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)
The number of days from study day 1 to death. Patients who had not died (no record of death) or were lost to follow-up were censored at the date of last contact.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jul 2008 (estimated)
- Study startJul 2008
- Primary completionApr 2011
- Study completionSep 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Carcinoma, Transitional CellStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Acrotech Biopharma Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Garry Weems, Pharm.D., Study director, Spectrum Pharmaceuticals, Inc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00722553
- Sponsor's protocol ID
- PDX-011
- Other IDs
- 2007-004671-19
- Status last verified
- Dec 2019
- First submitted
- 23 Jul 2008
- Last updated
- 17 Dec 2019
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Single-Arm Study of Pralatrexate in Patients With Advanced or Metastatic Relapsed Transitional Cell Carcinoma of the Urinary Bladder
- ClinicalTrials.gov ID
- NCT00722553
- Acronym / sponsor ID
- PDX-011
- Keywords
- Transitional Cell Carcinoma of the Urinary Bladder, Transitional Cell Carcinoma, Bladder Cancer, Urinary Bladder Cancer, Bladder, Carcinoma, Urinary, Metastatic
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Acrotech Biopharma Inc.Industry (pharma, biotech, devices)
- Study start
- Jul 2008
- Primary completion
- Apr 2011 (actual)
- Study completion
- Sep 2011 (actual)
- First posted
- 25 Jul 2008 (estimated)
- Results
- Posted 17 Jul 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Dietary Supplement Vitamin B12 & Folic Acid (Vitamin B9) | Other | Drug: Pralatrexate Injection, Dietary Supplement: Vitamin B12, Dietary Supplement: Folic AcidVitamin 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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.
Key exclusion criteria (14 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pralatrexate InjectionAlso: FOLOTYN, PDX, Pralatrexate, (RS)-10-propargyl-10-deazaaminopterinIntravenous (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. | Drug | Dietary Supplement Vitamin B12 & Folic Acid (Vitamin B9) |
| Vitamin B12Also: Cyanocobalamin1 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. | Dietary supplement | Dietary Supplement Vitamin B12 & Folic Acid (Vitamin B9) |
| Folic AcidAlso: Vitamin B9, Folate, Folacin1-1.25 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. | Dietary supplement | Dietary Supplement Vitamin B12 & Folic Acid (Vitamin B9) |
Primary outcome
Objective Response Rate (ORR)
Time frame: 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.
The number of patients with a best overall confirmed response of either complete response (CR) or partial response (PR)
4 secondary outcomes
Duration of Response (DOR)
Time frame: Measured from the first day of documented response for up to 2 years after enrollment.
Clinical Benefit Rate (CBR)
Time frame: 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)
Time frame: 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)
Time frame: 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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Garry Weems, Pharm.D. study director
Spectrum Pharmaceuticals, Inc
19 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pralatrexate Injection, Vitamin B12 and Folic Acid in people with Carcinoma, Transitional Cell and Bladder Cancer, run by Acrotech Biopharma Inc. at 19 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 19 sites in France, United States, Croatia, Spain, Argentina and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Jul 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) (time frame: 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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Dec 2019.